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Tissue Repair and Reconstruction

Andy H. Choi

Bone Remodeling
and Osseointegration
of Implants
www.dentalbooks.co

Tissue Repair and Reconstruction

Series Editors
Andy H. Choi, Carlingford, NSW, Australia
Besim Ben-Nissan, Sydney, NSW, Australia
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SpringerBriefs in Tissue Repair and Reconstruction provides a unique perspec-


tive and in-depth insights into the latest advances and innovations contributing to
improved and better treatments for patients with damaged soft and hard tissues as a
result of diseases, trauma, and implantations. The book series consists of volumes
that offer biomedical researchers better insights into the advancements of bioma-
terials science and their translation from the laboratory to a clinical setting. Simi-
larly, the series provides information to surgeons and medical practitioners on novel
ideas in biomedical science and engineering on top of disseminating new ideas and
know-hows in diagnostics and treatment options for patients from head to toe.
The series will cover a number of key topics:
Fundamental Concepts and Surface Modifications: The topic will provide detailed
information on the discovery and advancements of biomaterials surface modifica-
tion approaches and their use within the human body in a safe manner and without
provoking any negative tissue response.
Computational Simulations and Biomechanics: Anatomically accurate compu-
tational models are being in all fields of medicine particularly in orthopedics and
dentistry to reveal the biomechanical functions and behaviors of bones and joints
when damaged, diseased, and in the health state. They also contribute to our under-
standing during the design and applications of implants and prosthetics subjected to
functional loadings and movements.
Surgical Advances and Treatment Options: Discusses how surgical techniques are
revolutionized by our deeper understanding into biomaterials science and tissue engi-
neering. The section also focuses on the latest innovations and surgical advancements
currently being used to treat patients with damaged tissues.
Post-Operative Treatment and Rehabilitation Engineering: Expands the indepen-
dence and functionality of the patient after surgery while at the same time reducing
the chance of complications such as wound infections and dislocations. Advances
in technologies are creating new opportunities in how physiotherapy rehabilitations
are delivered.
www.dentalbooks.co

Andy H. Choi

Bone Remodeling
and Osseointegration
of Implants
www.dentalbooks.co

Andy H. Choi
School of Life Sciences
University of Technology Sydney
Sydney, NSW, Australia

ISSN 2731-9180 ISSN 2731-9199 (electronic)


Tissue Repair and Reconstruction
ISBN 978-981-99-1424-1 ISBN 978-981-99-1425-8 (eBook)
https://doi.org/10.1007/978-981-99-1425-8

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether
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The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
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The publisher, the authors, and the editors are safe to assume that the advice and information in this book
are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or
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Singapore
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Preface

Originally introduced as a technique used to solve structural mechanics problems,


finite element analysis (FEA) was quickly recognized as a universal procedure of
numerical approximation to all physical problems that can be modeled by a differen-
tial equation description. It has been accepted that the theory behind the bone remod-
eling sequence is to maintain the integrity of the skeleton. Key phases of fracture
healing have previously been examined using mathematical modeling and FE simu-
lations. The application of numerical models to simulate the fracture healing process
may prove to be advantageous in defining the optimal mechanical-based treatment or
reconstruction after an accident or illness. Furthermore, FEA is also widely utilized
to simulate the bone remodeling process as well as the osseointegration at the bone-
implant interface following implantations. During the first year of function, bone
remodeling will occur in response to occlusal forces and to establish normal dimen-
sions of the peri-implant soft tissues. This is of vital significance as the application
of implants may alter the mechanical environment of the surrounding bone tissue.
Changes in the internal stress state will govern whether constructive or destructive
remodeling will take place in the bone tissue surrounding the implant. Consequently,
it is imperative that the effect of bone remodeling is taken into consideration when
determining the performance and efficacy of implants and prostheses.
On the other hand, biomechanical simulations based simply on FEA will need
substantial amounts of time and powerful computing hardware thus making it not
as ideal in clinical settings where real-time responses are required. Furthermore, an
insufficient quantity of mathematical models is currently available that incorporates
bone structural information at various scales. Hence, a more thorough examination
of the bone remodeling process can be achieved only if bone structures on multiple
levels (macro, micro, and mesoscale) are included into the computational models.
It has been suggested that the utilization of artificial intelligence can address the
issue associated with the extensive computational resources needed during biome-
chanics and bone remodeling simulations. With proper training and testing, FEA
combined with artificial intelligence can be used in applications such as predicting
the survivability of a particular dental implant design employed to restore the func-
tional needs of an individual patient or the bone healing and remodeling process

v
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vi Preface

within synthetic bone tissue engineering scaffolds used to treat large bone defects.
The clinical significance with such approach is that it could ease the computational
costs associated with the utilization of FEM in applications such as design optimiza-
tion where testing every possible design scheme is impractical. This is particularly
true when it comes to dental implants in which the stress developed at the bone-
implant interface is governed by a number of design variables such as materials used
and the implant geometry.
It is envisaged that this book will provide an in-depth examination of the latest
research and advances in bone remodeling algorithm and their incorporation into
FE models and the use of artificial intelligence to predict the osseointegration and
bone healing process. The book is also intent to offer a fundamental insight into the
biomechanical behavior of the mandible, which is crucial if appropriate prosthetic
devices and surgical techniques are to be further refined.
Finally, I would like to express my deepest gratitude to my friend, mentor, and
series co-editor Prof. Besim Ben-Nissan for his advice and support for more than
two decades. Also, I would like to give special thanks to Dr. Ramesh Premnath for
making the Tissue Repair and Reconstruction book series possible. I would also like
to acknowledge the team at Springer Publishing, especially Ramesh Kumaran, for
their help during the entire process of publication.

Sydney, Australia Andy H. Choi


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Contents

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2 The Finite Element Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.1 History Behind the Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.2 Mesh and Mesh-Free . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.3 General Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.4 Constructing the Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
2.5 Assigning Materials Properties of Bone . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.6 Issue with Non-linearity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.7 Accuracy of FEM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.8 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3 Understanding the Biomechanics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
3.1 Biomechanics of the Mandible . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
3.1.1 Hypotheses Based on Non-lever Action . . . . . . . . . . . . . . . . . . 25
3.2 Biomechanics of the Temporomandibular Joint . . . . . . . . . . . . . . . . . . 25
3.3 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
4 Mathematical Analysis of the Mandible . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
4.1 Tooth Contact and the Biting Force . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
4.2 Calculating Forces at the TMJ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
4.3 Barbenel’s Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
4.4 Pruim, De Jongh, Ten Bosch’s Analysis . . . . . . . . . . . . . . . . . . . . . . . . . 34
4.5 Throckmorton and Throckmorton’s Analysis . . . . . . . . . . . . . . . . . . . . 37
4.6 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

vii
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viii Contents

5 Understanding Bone Structures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41


5.1 Bone Healing Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
5.2 Fracture Healing and Numerical Simulation . . . . . . . . . . . . . . . . . . . . . 49
5.3 Bone Remodeling Around Dental Implants . . . . . . . . . . . . . . . . . . . . . . 52
5.3.1 Strain Energy Density . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
5.3.2 Mechanobiological Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
5.3.3 Stanford Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
5.4 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
6 Patient-Specific Modeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
6.1 Mechanical Properties of Bone Tissue from CT Scans . . . . . . . . . . . . 73
6.1.1 Hounsfield Units to Density . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
6.1.2 Cortical Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
6.1.3 Cancellous Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
6.2 Muscle Forces and other Boundary Conditions . . . . . . . . . . . . . . . . . . . 79
6.3 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
7 Artificial Intelligence, Machine Learning, and Neural Network . . . . . . 83
7.1 Fuzzy Logic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
7.2 Machine Learning and Neural Network . . . . . . . . . . . . . . . . . . . . . . . . . 86
7.3 Predicting the Osseointegration Process . . . . . . . . . . . . . . . . . . . . . . . . . 88
7.4 Design Optimization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
7.5 Bone Healing and Remodeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
7.6 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
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Chapter 1
Introduction

Dental and orthopedic implant systems with predictable long-term results backed
by sound scientific research in addition to clinical trials are currently available. The
manner in which mechanical stresses are transferred from the implant to the surround
bone structure without creating forces of an extent that could potentially threaten the
longevity of the implant and/or prosthesis will determine its success from a clinical
perspective [1, 2].
For more than forty years, there has been a steady increase in the application of
dental implants. This interest has motivated the development of a variety of implant
designs and several new dental systems. Designing different categories of implants
is now made possible through the application of modern engineering techniques as
well as the utilization of computational modeling and simulations.
Replacing missing teeth successfully is one of the biggest challenges facing dental
professionals. Conventional full dentures may not stress bone properly resulting in
inflammation of soft tissues and a reduction in alveolar bone height [3–10]. Despite
the fact that implants have been used to support dental prostheses for a number of
years, they have not always enjoyed a favorable reputation. However, this situa-
tion has dramatically changed with the development of endosseous osseointegrated
dental implants. They are the nearest replacement equivalent to the natural tooth and
are a useful addition in the management of patients who have missing teeth as a
consequence of diseases, development anomalies, or trauma [11].
It is of paramount importance to determine the conditions of success for implant
systems as well as testing implants in well-controlled clinical trials. The most obvious
sign when an implant system is failing is mobility and its impact on the surrounding
bone tissues. The restoration of dentition by providing a way of transmitting masti-
catory forces to the maxillary or mandibular bone is the primary function of a dental
implant system. The significance of gaining an insight into the way in which the
stresses acting in a dental implant and how it is distributed into the surrounding bone
tissues is of vital importance in the field of prosthetic replacement where the primary
intent is to replace a damaged tooth so that the patient can effectively function.

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A. H. Choi, Bone Remodeling and Osseointegration of Implants, Tissue Repair
and Reconstruction, https://doi.org/10.1007/978-981-99-1425-8_1
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2 1 Introduction

Bone remodeling will occur during the first year of function in response to occlusal
forces in addition to creating normal dimensions of the peri-implant soft tissues. The
determination of whether destructive or constructive bone remodeling that will take
place lies in the changes in the internal state of stress in bone due to occlusal forces.
Abnormally high concentrations of stress in the supporting tissues can lead to patient
discomfort, pressure necrosis, and eventually failure of the implant system. On the
other hand, disuse atrophy similar to the loss of alveolar crest after the removal or
natural teeth could be the consequence of low stress levels around a dental implant
[12]. Typically, a definite landmark on the implant such as the implant-abutment
junction is used to determine the “ideal” bone level. As a result, it may differ between
implant systems.
Furthermore, quantifying minute changes in bone levels such as 0.2 mm per year
is impossible using conventional radiographs, and it is generally believed that bone
levels are to be more or less stable. Therefore, these specified changes are appropriate
in defining the average or mean changes across a large number of implants instead
of an individual implant. For example, an obvious change of one mm or more can
happen in a very small number of implants compared to the majority that remained
unchanged or in a steady state. In addition, it is also problematic in specifying the
conditions required to signify failure for an individual implant based on the levels
of change over a given period. An accelerated change in bone level may result in
stability for an extended period. Conversely, progressive or continuous bone loss is
a troublesome sign of imminent failure. Hence, it can be stated that an implant with
obvious loss of bone may be considered as “surviving” instead of “successful.”
The design of the implant will greatly influence its initial stability and subsequent
function [3]. The key design parameters are:
1. Shapes of the implants such as solid or hollow cylinders and solid or hollow
screws are designed to offer adequate stability during the early stages of implanta-
tion and maximizing the potential area for osseointegration. Osseointegration, by
definition, is the direct structural and functional connection between the ordered,
living bone and the surface of a load-carrying implant. Screw-shaped implants
also provide sound distribution of load characteristics during function. Even
minor variations in the size and pitch of the threads can improve the initial
stability.
2. Surface feature is another design parameter that will influence the degree of
osseointegration of the dental implant. There is the option of increasing surface
contact with bone through an increase in surface roughness. Yet, one has to keep
in mind that the tradeoff for this increase is the amount of bacterial contamination
on the implant surface if it becomes exposed within the oral cavity as well as the
increase likelihood of surface corrosion and ionic exchange.
3. Implant lengths are available from 6 mm up to 20 mm. Implant lengths between
8 and 15 mm are frequently used as they correspond quite closely to normal root
lengths.
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1 Introduction 3

4. The diameter of an implant can be as high as 6 mm, which are considerably


stronger and are available for clinical applications. However, they are not used
extensively due to the fact that sufficient bone width is not encountered regularly.
A minimum of 3.25 mm in diameter is required to ensure adequate implant
strength. Most implants are approximately 4 mm in diameter.
Implant stability is extremely important at the time of implantation, and variables such
as the design of the implant in addition to the quantity and quality of the surrounding
bone tissue will govern this stability. Following the loss of a tooth, the width and
height of the alveolar bone will begin to resorb. The most beneficial situation for
implant treatment would ideally consists of a well-established cortex and densely
trabeculated medullary spaces with a good blood supply. Good initial stability may
also be offered by bone tissues that are predominately composed of cortical bone.
In this case, extra precaution must be taken to avoid overheating during the drilling
process in particular for sites that are more than 10 mm in depth as the bone can
be damaged easily. On the other hand, bone with a thin or absent cortical layer and
sparse trabeculation will offer very poor initial implant stability. Such bone offers
very few cells with adequate osteogenic potential for promoting osseointegration.
Furthermore, the quality of bone is compromised by factors such as infection, heavy
smoking, and irradiation.
The rate of success for dental implantation can also be improved by using surgical
approaches that avoids heating the bone tissue. Damage to bone tissue occurs after one
minute at a temperature of approximately 47 °C, but this can be avoided by utilizing
slow drilling speed, successive incrementally larger sharp dills, and copious saline
irrigation.
Measuring the cutting torque during the preparation of the implant site can be
used to determine the bone quality. The stability of an implant as well as improving
the bone-to-implant contact has been examined using resonance frequency anal-
ysis [3]. This non-invasive tool evaluates the stiffness across the interface between
bone and implant. Moreover, it has been demonstrated that immediate loading is
consistent with subsequent successful osseointegration under certain conditions such
as adequate bone quality and if the functional forces can be properly controlled
[3]. Abutments are connected to the implant after the recommended healing period
of around three months to allow the construction of prosthesis. Subsequently, this
procedure prevents further surgery to uncover the implants.
It is important to note that the implant should not be excessively loaded during the
early healing phase following its installation. Currently, we cannot quantify accu-
rately or precisely determine the optimum period of healing before loading can begin.
Any movement of the implant within the bone during this stage will result in fibrous
tissue encapsulation instead of osseointegration. Similarly, this is somewhat compa-
rable to the healing of a fracture where stabilization of the bone fragments is of vital
importance in promoting union.
Increases in bone-to-implant contacts as well as sustaining osseointegration are
possible through carefully planned occlusal loading during functional movements.
In contrast, insufficient load transfer or too much loading can result in bone loss
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4 1 Introduction

and/or component failure. Parafunctional activities as well as the design of the pros-
thesis are two primary factors that can lead to implant overload. Excessive occlusal
forces created in either or both circumstances present opportunities for loosening
and/or fracture of the screws through bending overload [13]. Bending overload can
be described as a situation where occlusal forces on an implant-supported prosthesis
exert a bending moment resulting from non-axial loading on the implant cross-section
at the crestal bone level [14].

1.1 Concluding Remarks

Currently, one of the major drawbacks of synthetic implants is their inability to adapt
to the local tissue environment. The primary factors in determining the potential
applications of a biomaterial are its functionality and biocompatibility. Additional
considerations such as its aesthetics and mechanical capability are needed when
choosing a biomaterial to be used as a dental implant. Dental implants of today need
to demonstrate effective osseointegration and maintain long-term stability of their
favorable properties to preserve both the structure of the implant and the integrity
of surrounding bone tissues. Based on their chemical and physical properties, tita-
nium and its ternary alloys such as Ti-6Al-4 V and more recently TiZr appear to
be particularly ideal for dental implants and prostheses. The passivating oxide on
the implant surface permits intimate apposition of hard and soft tissues, physiolog-
ical fluids, and proteins to the titanium surface. To address the concerns centered
on aesthetics, dental implants manufactured from the bioceramic zirconia (partially
stabilized zirconia) are a non-metal alternative to titanium implants.

References

1. Semisch-Dieter OK, Choi AH, Ben-Nissan B et al (2021) Modifying an implant: a mini-review


of dental implant biomaterials. BIO Integration 2:12–21. https://doi.org/10.15212/bioi-2020-
0034
2. Choi AH, Ben-Nissan B (2018) Anatomy, modeling and biomaterial fabrication for dental and
maxillofacial applications. Bentham Science Publishers, United Arab Emirates
3. Palmer R (1999) Introduction to dental implants. Brit Dent J 187:127–132
4. Palmer R, Howe L (1999) Assessment of the dentition and treatment options for the replacement
of missing teeth. Brit Dent J 187:247–255
5. Palmer P, Palmer R (1999) Implant surgery to overcome anatomical difficulties. Brit Dent J
187:532–540
6. Palmer R, Palmer P, Floyd P (1999) Basic implant surgery. Br Dent J 187:415–421
7. Albrektsson T, Sennerby L (1991) State of the art in oral implants. J Clin Periodontol 18:474–
481
8. Atkinson PJ, Woodhead C (1979) Remodeling in the aging mandible. J Implantol 8:372–383
9. Hudis MM (1978) The mouth: medical consideration in the construction and design of oral
prostheses. Ann Dent 37:45–56
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References 5

10. Schnitman A, Shulman LB (1977) Dental implants: their current status. J Mass Dent Soc
26:278–286
11. Skalak R (1983) Biomechanical considerations in osseointegrated prostheses. J Prosthet Dent
49:843–848
12. Grenoble DE (1974) Design criteria for dental implants. Oral Implantol 5:44–64
13. Haack JE, Sakaguchi RL, Sun T et al (1995) Elongation and preload stress in dental implant
abutment screws. Int J Oral Maxillofac Implants 10:529–536
14. Rangert BR, Sullivan RM, Jemt TM (1997) Load factor control for implants in the posterior
partially edentulous segment. Int J Oral Maxillofac Implants 12:360–370
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Chapter 2
The Finite Element Approach

The finite element technique is a numerical method used to investigate structures and
continua. Generally, the problem at hand is too difficult to be resolved in an acceptable
manner using classical analytical means. Initially introduced as an approach applied
to describe structural mechanics problems, finite element analysis (FEA) was quickly
recognized as a universal technique of mathematical approximation to all physical
problems that can be modeled by a differential equation description.
The FE approach was introduced in orthopedic biomechanics in the 1970s in an
effort to examine the stresses, strains, and deformation in human bones during func-
tional loadings. In dentistry, the utilization of FEA in areas such as the design and
analysis of implants and deformations during functional loadings accelerated after
the 1980s. Since then, it has been applied frequently in oral and maxillofacial surgery
in addition to orthopedics and spinal research to analyze problems such as implant
design, fracture healing, bone remodeling, and interactions at the bone-implant inter-
face. It has also been used to study the mechanical properties of biomedical nanocoat-
ings. More recently, it has been applied in nanomedicine to examine the mechanics of
a single cell and to gain fundamental understandings into how the particulate nature
of blood influences nanoparticle delivery [1, 2].

2.1 History Behind the Approach

A “lattice analogy” intended for stress analysis was first suggested by researchers in
1906. The continuum was replaced by a methodical pattern of elastic bars. Properties
of the bars were chosen in a way that produced displacements of the joints to estimated
displacements of points in the continuum. This approach worked toward exploiting
on well-known methods of structural analysis.
The finite element method (FEM) that we are all familiar today was initially
suggested by a German-American mathematician by the name of Richard L. Courant
[3]. In a lecture on mathematics in 1941 that was later published in 1943, piecewise

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A. H. Choi, Bone Remodeling and Osseointegration of Implants, Tissue Repair
and Reconstruction, https://doi.org/10.1007/978-981-99-1425-8_2
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8 2 The Finite Element Approach

polynomial interpolation over triangular subregions and the principle of stationary


potential energy was applied by Courant to investigate the Saint–Venant torsion
problem. The work of Courant was overlooked until it was further expanded afterward
by engineers independently [4].
None of the aforementioned work was of much practical value at the time as
computer power was not available to generate and resolve large series of simultaneous
algebraic equations. It was not accidental that major advances in digital computers
and programming language overlapped with the expansion of finite element analysis.
Engineers by 1953 had created and ascertained stiffness equations in matrix format
using digital computers. A large quantity of this work was conducted within the
aerospace sector. During that time, a large finite element (FE) problem consisted
of hundred degrees of freedom. In 1953 at the Boeing Airplane Company, Turner
suggested that a triangular plane stress element could be utilized to model the skin
of a delta wing. Published almost at the same time with similar work performed in
England, this work signifies the beginning of the widespread application of finite
element analysis. As a consequence of company policies against publication, much
of this early work went unrecognized [5–7].
The phrase “finite element method” was invented by Clough in 1960, and it was
becoming clear the practical value of the method. New elements designed for the
purpose of stress analysis were created mainly by intuition and physical argument.
In 1963, the method gained respectability when it was recognized as having a sound
numerical foundation, and it can be considered as the explanation of a variational
problem through the minimization of a function. Subsequently, the method was being
applied to all field problems that can be modeled in a variational form [8, 9].
Large general-purpose FE computer programs emerged during the late 1960s
and early 1970s, and examples of such programs include ANSYS, ASKA, and
NASTRAN. Every one of these programs contained many different forms of elements
and can carry out heat transfer, dynamic, and static investigations. Extra capabil-
ities were quickly incorporated. In addition, pre-processors (for data input) and
post-processors (for result evaluation) were also included. These processors rely
on graphics; hence, performing finite element analysis was cheaper, quicker, and
easier. During the early 1980s, the development of graphics became intensive as
software and hardware for interactive graphics became affordable and accessible.
Typically, a general-purpose FE program contains over hundred thousand lines of
codes and normally resides on a superminicomputer or a mainframe. Adaptations of
general-purpose programs began to appear on personal computers during the mid-
1980s, and FE calculations can now be carried out on personal computers, laptops,
mainframes, and cloud-based computing services [10]. Hundreds of analyses and
analysis-related programs are now available, for purchase or for lease, cheap or
expensive, general or narrow, large or small.
One has to keep in mind that the results obtained from FE simulations are seldom
precise. However, by processing more equations, errors are reduced and results
sufficiently accurate for engineering applications are attainable at reasonable costs.
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2.2 Mesh and Mesh-Free 9

2.2 Mesh and Mesh-Free

Finite element analysis examines a complex problem by redefining it as the summa-


tion of the solutions of a series of interrelated simpler problems. The first step involves
subdividing (or discretize) the complex geometry into a suitable set of smaller “ele-
ments” of “finite” dimensions. This creates the “mesh” model of the investigated
structure when combined (Fig. 2.1).
Each element can take on a specific geometric shape (for instance, cube, triangle,
tetrahedron, square, etc.) with an explicit internal strain function. The equilibrium
equations between the external forces acting on the element and the displacements
taking place at its corner points or “nodes” can be described using these functions, the
actual geometry of the element, and a suite of boundary conditions such as constrain
points. Each node of the element will generate one equation for each degree of
freedom. Typically, these equations are properly written in matrix form for use in a
computer algorithm.
From the example in Fig. 2.1, and as a whole, the FE approach models a structure
as an assembly of small parts or elements. A simple geometry is utilized to define
each element, and hence, it is much easier to investigate than the actual structure.
Fundamentally, FEM approximates a complex situation using a model that comprises
of piecewise-continuous simple solutions. Elements are called “finite” to distinguish
them from differential elements used in calculus.
The creation of a three-dimensional (3-D) FE mesh has been widely acknowledged
as a task that is the most labor intensive and time consuming. Even with the use of the
most sophisticated mesh-generator, time remains limitless. It is possible to obtain
a mesh very quickly for a given distribution of points. However, low quality or
distorted meshes result in greater chances of producing errors in the analysis; hence,
remeshing is necessary, and this might not be feasible for complex 3-D geometries
in finite time. Furthermore, mesh-based FE approach is not ideal to solve problems
with discontinuities that do not align with element edges. Again, one approach in
dealing with this issue is remeshing [11, 12].

Fig. 2.1 a Solid model and b finite element mesh model (b) of a dental implant
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10 2 The Finite Element Approach

As a result, meshless (or mesh-free) approach was introduced aimed at removing


some of the difficulties related to the need of a mesh to construct the approximation.
Discrete points instead of tetrahedron mesh are used in the meshless method for
representing continuum, and the partial differential equations are solved by taking
the advantages of interpolation methods [12]. In the meshless approach, large defor-
mation can be managed more robustly and issues with moving discontinuities such
as crack propagation can be handled with relative ease. Above all, mesh alignment
sensitivity is negligible [11]. A number of meshless techniques have been suggested
and they can be categorized according to the definition of the shape functions and/or
based on the minimization method of approximation. The minimization may be via a
weak form (as in the Galerkin methods) or a strong form (as in the Point Collocation
approach) [12]. Nonetheless, there are a number of disadvantages associated with
the meshless method. The shape functions are rational functions that involves high-
order integration scheme to be computed accurately. Furthermore, handling important
boundary conditions is not as straightforward as in mesh-based approaches since the
shape functions in the meshless method are not interpolants and do not satisfy the
Kronecker delta property [11, 13]. This results in an increase in the computational
cost of the analysis as the essential boundary conditions cannot be imposed directly
in the system of equations [14].
On the other hand, the remeshing efficiency in the meshless methods enables
the analyses of soft materials such as muscles and the resultant large distortions in
comparison to the finite element approach. Furthermore, the smoothness and accu-
racy of the stress fields obtained with the meshless methods are extremely useful in
predicting the remodeling process of biological tissues [15–18]. The natural element
method (NEM), a meshless method based on the natural neighbor concept to define
the shape functions [19], has been suggested to be more advantageous over the FEM
when it comes to problems that involves complex geometries or large mesh distor-
tions where the design of the mesh is costly. Another advantage of NEM is its ability
to be easily coupled with finite element and implemented into any FEA frameworks
[20]. This approach was applied by Doweidar et al. to examine aspects where NEM
is competitive with FEA such as modeling of human articular joints like the knee
[20].
Another meshless method that can be used to study the bone remodeling process
is based on the combination of NEM and the radial point interpolation method
(RPIM) [14, 21]. RPIM is based on the Galerkin weak form formulation utilizing
3-D mesh-free shape functions generated using radial basis functions. More impor-
tantly, essential boundary conditions can be enforced as easily as in the FE approach
since the RPIM shape functions have the Kronecker delta functions property [22].
The proposed method known as natural neighbor radial point interpolation method
(NNRPIM) has been suggested to be useful in the micro and macroscale bone
tissue remodeling analysis [17, 23]. According to the authors, a nodal distribu-
tion is only needed in NNRPIM. The initial nodal distribution is used to construct
all the other numerical structures needed to solve the problem. This approach is
more suitable to discretize highly irregular domains such as biological structures
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2.3 General Principles 11

compared to conventional mesh-dependent numerical approaches [18, 21]. Addition-


ally, NNRPIM allows a total random node distribution for the discretized problem
unlike in FEM where geometrical restrictions on elements are enforced for the
convergence of the method [16].

2.3 General Principles

The FE method is an approach of piecewise calculation in which the approximating


function φ is generated by linking simple functions, each defined over a small region
(element). A finite element is a region in space where a function φ is introduced
from nodal values of φ on the boundary of the region in a fashion that interelement
continuity of φ to be preserved in the assembly.
In general, a FE analysis consists of the following steps. Certain stages during
the analysis will require decisions by the analyst as well as providing input data for
the computer program (steps 1, 4, and 5), while others are carried out automatically
(steps 2, 3, 6, and 7) [1]:
1. Divide the continuum or structure into finite elements. Built-in mesh generation
function or external meshing programs such as MeshLab will assist the user in
performing this task.
2. Formulate the properties for each element. In stress analysis, this means deter-
mining nodal loads associated with all element deformation states that are
allowed.
3. Assemble elements to obtain the finite element model of the structure.
4. Application of known loads (nodal forces and/or moments in stress analysis).
5. Specify how the structure is supported. In stress analysis, this stage involves
fixing several nodal displacements to known values, which are often zero.
6. Solve simultaneous linear algebraic equations to determine nodal degrees of
freedom. In stress analysis, it is nodal displacements.
7. In stress analysis, compute element strains from the nodal degrees of freedom and
the element displacement field interpolation and finally calculate stresses from
strains. Outputs are sorted and displayed in graphical form by the software’s
post-processor.
In the meshless method, Belinha has summarized the typical procedure used to
solve problems such as bone tissue remodeling analysis [24]:
1. Discretize the problem domains into nodes and the accuracy and performance
will be strongly influenced the manner in which this is carried out.
2. Utilizing a Gaussian integration scheme or other integration numerical tech-
niques, construct the background integration mesh to amalgamate the weak form
equations.
3. Impose nodal connectivity via influence domains. Every integration point will
have its own influence domain that is formed by the set of nodes near that point.
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12 2 The Finite Element Approach

Again, the performance of the meshless method will be affected greatly by the
shape and size of the influence domain.
4. The influence domain of that integration point is used to create the shape
functions.
5. Approximation functions are used to obtain the field variables.
6. The nodal-based system of equations is created through the assembly of local
nodal matrix into the global equation system matrix.
7. Finally, solve the discrete system using an appropriate solver.

2.4 Constructing the Model

The projected response of the FE model depends on choosing the most appropriate
type of elements and therefore achieving the goals set out for the analysis such as
stress analysis. Subsequently, a wide diversity of different types of elements is offered
by FEA, and they can be categorized according to family, order, and topology.
The element family refers to the characteristics of displacement and geometry that
the element is attempting to model. Among the most common families used for typical
structural models are one-dimensional (1-D) beam elements, two-dimensional (2-D)
plane stress and plane strain elements, axisymmetric elements, and 3-D solid and
shell elements.
Beam elements are helpful in modeling beam-like structures where length is much
greater than other dimensions and the overall deflection and bending moments can
be calculated. This type of model however will not be capable of predicting the local
stress concentrations at the point of application of a load or at joints. Plane stress
elements are ideal for thin 2-D structures where stresses out of the plane can be
ignored. Plane strain elements simulate a special 3-D stress state taking place when
out-of-plane deformation is constrained (for instance in relative thick plates).
By utilizing well-defined characteristics of an axisymmetric geometry, 3-D stress
fields can be modeled and simulated under 2-D conditions through the use of axisym-
metrical elements. Shell elements can be used effectively for 3-D structures that are
thin in comparison to other dimensions, such as sheet metal parts in which bending
and in-plane forces are vital. These elements on the other hand will not predict stresses
that changes through the thickness of the shell due to local bending effects. All 3-D
conditions should ideally be modeled using solid elements. However, the order of
magnitude of such a solid model may impose practical limits on the choice of those
elements due to the computational effort of most FE solvers is roughly proportional
to the number of equations and the square of the bandwidth. Thus, an acceptable
reduction of a 3-D situation should be considered seriously in each FE analysis.
Elements can also be classified according to order. Along each edge, linear
elements have two nodes, while parabolic have three. Lower-order elements are
stiffer than higher-order elements and this is related to bending as having more
nodes will provide more degrees of freedom. A degree of freedom signifies the
liberty of rotational or translatory motion of a particular node in space. For instance,
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2.5 Assigning Materials Properties of Bone 13

shell elements have six degrees of freedom at each of their unrestrained nodes (three
translations [x, y, and z] and three rotations around the x-, y-, and z-axes). Conversely,
the unrestrained nodes in 3-D (solid) elements have only three translational degrees
of freedom, and 2-D elements have only two. An increase in the number of degrees of
freedom results in more variables in the stiffness formulation, and it is more computer
intensive. Higher-order elements produce more accurate results for an equal mesh
grid, but a finer grid of lower-order elements can end up to be more efficient with
the same accuracy.
Element topology refers to the general shape of the element, for example, quadri-
lateral or triangular. The topology is also determined by the family of the element
(i.e., 2-D or 3-D). Typically, quadrilateral elements could be considered more ideal
than triangular elements in complex structural models as the quadrilateral can match
the true displacement functions more accurately due to a higher number of degrees
of freedom. Moreover, the number of elements in meshes tends to be higher if
constructed from triangular elements. The simplicity of triangular elements on the
other hand makes them very attractive particularly in automatic mesh generation.
Triangular-shaped elements are easier to fit into geometrically complex structures.
The combination of various element topologies and element orders (such as triangular
and parabolic) can improve the accuracy of a topologically lesser element.
Since any deviation in shape from the “ideal” internal elemental strain function
will contribute to mathematical inaccuracies, the predictive accuracy of the FE model
will be determined by the shape of the elements. Since FEA offers an approximation
to the exact solution, a numerical result closer to this true value can be achieved if the
displacements in a FE model becomes increasingly continuous. A vital component in
FEA is the behavior of the individual elements. A few good elements may generate
better results than many poorer elements.

2.5 Assigning Materials Properties of Bone

The predictive accuracy of a FE model also lies in the proper assignment of material
properties, as stresses and strains within a structure are calculated based on the
materials properties. These properties can be categorized as isotropic, anisotropic,
orthotropic, and transversely isotropic.
The mechanical properties are the same in all directions for an isotropic material,
and given the fact that the Young’s modulus, Poisson’s ratio, and the shear modulus
are interrelated, only two out of the three variables need to be determined for the
elastic behavior to be characterized completely. A material is classed as anisotropic
if its properties are different when evaluated in different directions. An orthotropic
material is an anisotropic material that demonstrates extreme values of stiffness
in mutually perpendicular directions. These directions are referred to as principal
directions of the material. The Young’s modulus for an orthotropic material contains
only nine independent coefficients. A material is considered as transversely isotropic
if it behaves in the same way in every direction about a single axis of symmetry.
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14 2 The Finite Element Approach

A constitutive relationship exists that connects the components of stress to the


components of strain. The constitutive relationship seems to be sufficient for bone if
it is believed as an anisotropic, inhomogeneous, and linearly elastic material [25].
Information on the mechanical properties of the mandible has been determined
on small specimens obtained from human tibiae and from the mandibles of cadavers
and humans using materials testing methods [26–32] and ultrasonic wave techniques
[33–39].
Values of elastic constants reported in a number of studies are summarized in
Table 2.1. Using a material testing approach, Arendts and Sigolotto noticed that
the mandible is stiffer and stronger in the longitudinal direction than the radial and
tangential directions after examining specimens obtained at various regions in three
mandibles. They suggested that this could be the result of the orientation of osteons,
apatite crystals, and collagen fibers [31, 32]. Similar observations were made when
the relationship between muscle attachments in the mandible, and the orientations
of apatite crystals were reported [40].
Using a continuous-wave ultrasonic approach, parallelepiped specimens taken at
ten different locations in the mandible were tested [41]. Data on the elastic properties
revealed that the human mandibular bone is elastically homogeneous but anisotropic
and the mandible seems like a slightly less stiff long bone bent into the shape of
a horseshoe. Ultrasonic wave techniques were also used in another study in which
the Young’s modulus, Poisson’s ratio, and the shear modulus of 17 mandibles were
determined [42]. By utilizing the Archimedes principle of Buoyancy technique, the
density of each sample was calculated and an average density of 1.768 g/cc was
recorded from the mandible samples.

Table 2.1 Young’s modulus (E), shear modulus (G) in GPa, and Poisson’s ratio (υ) for the
human mandible. The 1-direction is radial, the 2-direction is circumferential, and the 3-direction is
longitudinal directions [31, 32, 41–43]
Arendts and Sigolotto Ashman and Van Buskirk Dechow et al. [42] Carter [43]
[31, 32] [41]
E1 6.9 10.8 11.3 13.0
E2 8.2 13.3 13.8 13.0
E3 17.3 19.4 19.4 19.0
G12 3.81 4.5 5.3
G13 4.12 5.2 5.9
G23 4.63 6.2 5.9
υ12 0.270 0.309 0.274 0.22
υ13 0.125 0.249 0.237 0.29
υ21 0.150 0.381 0.317 0.22
υ23 0.325 0.224 0.273 0.29
υ31 0.310 0.445 0.405 0.42
υ32 0.315 0.328 0.376 0.42
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2.5 Assigning Materials Properties of Bone 15

Table 2.2 Young’s modulus of cortical bone (in GPa) determined using acoustic microscopy and
nanoindentation technique (data are reported as mean ± standard deviation) [29, 44]
Turner et al. [29] Rupin et al. [44]
Direction Longitudinal Transverse Transverse
Acoustic 20.55 ± 0.21 14.91 ± 0.52 35 ± 11
Nanoindentation 23.45 ± 0.21 16.58 ± 0.32 19.5 ± 3

Nanoindentation is another technique that can be employed to estimate the


Young’s modulus of human bone at a microstructural level, but the results obtained
may not be accurate due to the method determines the Young’s modulus with the
assumption that the material behaves in an elastically isotropic manner [29]. Despite
the capability of nanoindentation in providing elastic and post-yield properties of
bone, it is a destructive method. On the other hand, scanning acoustic microscopy is
an attractive non-destructive and non-contact quantitative alternative to map linear
elastic properties [37]. A face-to-face comparison was carried out in a study by
Rupin et al. between scanning acoustic microscopy and nanoindentation estimates
of Young’s modulus of cortical bone transverse cross-sections extracted from the mid-
diaphysis of the right femur [44]. They noticed that the Young’s modulus obtained
from acoustics was nearly two times higher than those obtained from nanoindenta-
tion, suggesting the difference could be due to the fixed assumed value of Poisson’s
ratio used in determining the acoustic Young’s modulus. On the contrary, the study by
Turner et al. showed the elastic moduli estimated using the nanoindentation approach
was between 4 to 14% higher than using acoustic microscopy [29] (Table 2.2).
It was previously suggested that the Young’s modulus of bone varies between
different anatomical regions within the human maxilla and mandible. Using nanoin-
dentation, bone samples from maxillary anterior, maxillary posterior, mandibular
anterior, and mandibular posterior were tested. Results of their study revealed that
the Young’s modulus of the mandible (18.3 GPa) was higher than the maxilla (14.9
GPa), and the Young’s modulus of the posterior jawbone (17.5 GPa) was higher than
anterior jawbone (15.7 GPa) [45].
In addition to the studies carried out on cortical bone, the mechanical properties
of cancellous bone have also been ascertained on various locations throughout the
human mandible as well as on other human bones such as the tibiae in a number of
investigations using a variety of mechanical testing techniques [28, 46–50].
Using the indentation approach with a stainless-steel indenter, regional variations
in the Young’s modulus of proximal tibia (both over the transverse plane and through
the depth of the epiphysis) were converted from stiffness measurements and the values
ranged from 4.2 to 1196.6 MPa with a mean and standard deviation of 331.4 MPa
and 312.6 MPa, respectively [46].
The orthotropic elastic properties of cancellous bone were determined using 75
specimens from three human proximal tibiae. A modified ultrasonic technique was
used to determine the Young’s moduli and shear moduli. A comparison was also
performed between the moduli measured ultrasonically to those measured in a tensile
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16 2 The Finite Element Approach

Table 2.3 Young’s modulus


Rho [49] Turner et al. [50] Nikodem [47]
(E), shear modulus (G) in
MPa, and Poisson’s ratio (υ) E1 202 (154) 316.7 147.41 (67.60)
of human cancellous bone E2 232 (180) 385.5 157.36 (118.81)
obtained using the ultrasonic
E3 769 (534) 959.3 174.26 (131.96)
approach and uniaxial
compression testing. The G12 88.7
works of Rho [49] and Turner G13 125.6
et al. [50] centered on human
proximal tibiae, while the G23 165.7
work of Nikodem [47] is υ12
based on the human femur. υ13
The 1-direction is radial, the
2-direction is circumferential, υ21
and the 3-direction is υ23 0.3
longitudinal directions (Note υ31 0.3
Standard deviation in
parentheses) υ32 0.3

test. Ultrasonic specimens were cut from the center of each tensile specimen and the
ultrasonic Young’s modulus was calculated [50]. A similar study was also conducted
by Rho in which the Young’s modulus of cancellous structures was measured using
ultrasonic techniques [49]. One hundred and forty-four cancellous bone specimens
were taken from the right proximal tibiae of eight frozen human cadavers. The study
showed the Young’s modulus of cancellous bone exhibited inhomogeneity and some
consistency pattern along both the length and the circumference of the proximal
tibiae (Table 2.3).
Non-destructive compressive mechanical testing was used in the study by
Nicholson et al. [48] to estimate the structural Young’s modulus of the cancellous
framework of 48 human vertebral bone cubes in the three orthogonal axes. Based on
their findings, significant mechanical anisotropy was observed with mean structural
Young’s modulus varied from 165 MPa in the supero-inferior direction to 43 MPa in
the lateral direction. Later, the Young’s modulus of cancellous bone was determined
in three orthogonal directions using bone tissues coming from the area of four human
femoral heads without lesions [47]. Uniaxial compression tests were performed on
the tissue specimens where the Young’s modulus in three orthogonal directions were
determined (Table 2.3). A failure test was also performed on the tissue samples in
the direction perpendicular to the neck-shaft angle of the hip joint with the purpose
of determining the ultimate compressive strength (11.36 ± 3.96 MPa).
The study by O’Mahony et al. used a fresh edentulous human mandible to deter-
mine the physical and mechanical properties in three orthogonal directions [28].
Small cubes of cancellous bone aligned with the infero-superior, bucco-lingual, and
mesio-distal axes were obtained. Samples were excised from seven anatomic sites
(pre-existing tooth positions) and tested non-destructively using compressive testing
to obtain a total of 21 Young’s moduli (Table 2.4). Prior to testing, cubes cut with
faces aligned with the anatomic axes were kept moist with buffered saline.
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2.6 Issue with Non-linearity 17

Table 2.4 Mechanical and physical properties of cancellous bone based on anatomical sites
according to O’Mahony et al. [28]
Anatomical Sites Young’s modulus (MPa) Apparent Density
Infero-Superior Bucco-Lingual Mesio-Distal (g/cm3 )

Left lateral incisor 105 160 312 0.40


Left central incisor 56 126 52 0.30
Right central 123 1113 2283 0.98
incisor
Right canine 48 71 140 0.23
Interior right 1st 262 1464 1768 0.75
premolar
Superior right 2nd 158 553 805 0.78
premolar
Right 2nd premolar 47 91 998 0.39

As mentioned previously, accurate data are needed to perform any FE modeling


and analyses related to bone tissue (such as bone remodeling, stress analysis at the
implant-bone interface). The use of medical imaging such as computed tomography
(CT) scans can offer a more appropriate approximation of the mechanical properties,
and this approach will be discussed further in the Patient-Specific Modeling chapter.

2.6 Issue with Non-linearity

In FEA, a problem is non-linear if the relationship between force and displacement is


dependent on the current state of the force, displacement, and stress–strain relations
[51]. Non-linearity in a problem or structure can be categorized as geometric non-
linearity, material non-linearity, and non-linearity due to boundary conditions.
Geometric non-linearity occurs when the relationships of displacements and
strains are non-linear with forces and stresses. This results in changes in structural
behavior and loss of structural stability. Examples are large displacement problems
and buckling.
Material non-linearity arises if stresses and strains are related by a strain-
dependent matrix instead of a matrix of constants. Consequently, the computational
difficulty is that equilibrium equations must be written using materials properties that
depend on strains, but strains are not known in advance. Plastic flow is frequently a
cause of material non-linearity.
Non-linearity induced by boundary conditions occurs when the load and the
resistance to the deformation induced by the loads that represent the effects of
the surrounding environment on the model. Boundary conditions can induce non-
linearity if they vary with displacement of the structure. A discontinuous character
is displayed in many of these non-linear boundary conditions, making them some
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18 2 The Finite Element Approach

of the most severe non-linearities in mechanics. Friction slip effects and contact are
some examples of non-linearity induced by boundary conditions.
The key difference between non-linear and linear FEA rests in the solution of
the algebraic equations. Compared to linear analysis, non-linear analysis is typically
more expensive and complex. Furthermore, results from non-linear analysis are not
always unique and normally require an iterative incremental solution strategy to
ensure that equilibrium is satisfied at the end of each step. Hence, this is completely
different to linear problems.
The categorizations “non-linear” and “linear” are artificial in that physical reality
presents different problems, some of which can be approximated satisfactorily by
linear equations. For many problems of stress analysis, it is fortunate that linear
approximations are quite adequate. Non-linear approximations are more challenging
to formulate, and solving the resulting equations could cost ten to one hundred times
as much as a linear approximation having the same number of degrees of freedom.
Numerous physical situations display non-linearities too great to be overlooked.
Stress–strain relations may be non-linear in either a time-independent or a time-
dependent way. An alternation in configuration may result in loads to change their
magnitude or distribution or cause gaps to open or close. Mating components may slip
or stick. Casting and welding processes cause the material to change in conductivity,
phase, and modulus. The generation and shedding of vortices in fluid flow past a
structure create oscillatory loads on the structure. Pre-buckling rotations change the
effective stiffness of a shell and alter its buckling load. Hence, it can be realized that
non-linear effects may vary in type and may be mild or severe.
The analyst performing any FE simulation and analysis must understand the phys-
ical problem and must be familiar with different solution strategies. A single strategy
will not always work well or may not work at all for certain problems. A number of
attempts may be required in order to obtain a satisfactory outcome.

2.7 Accuracy of FEM

The accuracy of the FEM can only be objectively established via a convergence
test. It is used to determine how well the mathematics has been approximated. The
approximate solution tends to improve as a series of meshes get more and more
refined in a process commonly referred to as h-convergence. As more elements and
nodes are used, the calculated displacement at any given node approaches the exact
but generally unknown displacement solution.

2.8 Concluding Remarks

FEA is widely used in all biomechanical fields, especially for assessing stresses and
strains in dental implants and the surrounding bone structures as well as in normal
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References 19

bone. The predictive accuracy of the FE model is influenced by the geometric detail of
the object to be modeled, the applied boundary conditions and the material properties
assigned. In recent years, a number of experimental investigations have been carried
out to determine the mechanical properties of both cortical and cancellous bone.
Due to the fact that bone is a heterogeneous, anisotropic material, the anatomical
location of the test specimen will greatly influence the experimental results. Testing
parameters such as the vibration frequency in ultrasonic tests, or the deformation
rate and the duration of load in mechanical tests will also play an important role
in governing the accuracy and reliability of the test results. Features also change
based on the type of bone, biological variables such as age, level of activity of the
living bone and its possible state of pathological degradation (such as osteoporosis),
in conjunction with the preservation conditions of the specimen until it is used for
experimentation, all resulting in an irregular distribution of its mechanical properties.

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20 2 The Finite Element Approach

15. Belinha J, Dinis LMJS, Natal Jorge RM (2015) The mandible remodeling induced by dental
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16. Belinha J, Dinis LMJS, Natal Jorge RM (2015) The meshless methods in the bone tissue
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17. Belinha J, Natal Jorge RM, Dinis LMJS (2013) A meshless microscale bone tissue trabecular
remodelling analysis considering a new anisotropic bone tissue material law. Comput Methods
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21. Dinis LMJS, Natal Jorge RM, Belinha J (2007) Analysis of 3D solids using the natural
neighbour radial point interpolation method. Comput Methods Appl Mech Eng 196:2009–2028
22. Liu GR, Zhang GY, Gu YT et al (2005) A meshfree radial point interpolation method (RPIM)
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measurement of the elastic properties of cortical bone. J Biomechanics 17:349–361
26. Giesen EBW, Ding M, Dalstra M et al (2001) Mechanical properties of cancellous bone in the
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27. Swadener JG, Rho JY, Pharr GM (2001) Effects of anisotropy on elastic moduli measured by
nanoindentation in human tibial cortical bone. J Biomed Mater Res 57:108–112
28. O’Mahony AM, Williams JL, Katz JO et al (2000) Anisotropic elastic properties of cancellous
bone from a human edentulous mandible. Clin Oral Impl Res 11:415–421
29. Turner CH, Rho J, Takano Y et al (1999) The elastic properties of trabecular and cortical
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30. Zysset PK, Guo XE, Hoffler CE et al (1999) Elastic modulus and hardness of cortical
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31. Arendts FJ, Sigolotto C (1990) Mechanical characteristics of the human mandible and study
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www.dentalbooks.co

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37. Raum K, Grimal Q, Varga P et al (2014) Ultrasound to assess bone quality. Curr Osteoporos
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the elastic properties of cortical bone. J Biomech 35:961–968
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42. Dechow PC, Nail GA, Schwartz-Dabney CL et al (1993) Elastic properties of human
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Company (UK) limited, London
www.dentalbooks.co
www.dentalbooks.co

Chapter 3
Understanding the Biomechanics

3.1 Biomechanics of the Mandible

Primarily responsible for speaking, swallowing, and chewing, the masticatory system
is a functional unit of the human body that consists of bones, teeth, muscles, liga-
ments, and joints. The mastication system is a highly complex and refined unit. In
order to study occlusion, it is essential to gain an in-depth understanding of its biome-
chanics and functional anatomy. The mandible is a horseshoe-shaped bone that is
suspended below the maxilla by muscles, ligaments, and other soft tissues, all of
which provide the mandible mobility necessary to function with the maxilla. The
mandible also supports the lower teeth and makes up the lower portion of the facial
skeleton. The muscles provide the energy needed to move the mandible and allows
function of the masticatory system. Four pairs of muscles situated on the left and
right side of the mandible form a group commonly referred to as the muscles of
mastication.
The most frequently used biomechanical analogy for the mandible has been the
Class III lever, in which the condyle acts as a fulcrum, the masticatory muscles as
applied force, and the bite pressure as resistance (Fig. 3.1) [1].
The Class III lever requires that the bite force be less than the applied force
(e.g., the masseter and temporalis) to reach mechanical equilibrium in order for the
masticatory “machine” to have a mechanical advantage of less than one.
The notion of the believe that the mandible acts like a Class III lever has however
been questioned by other researchers based on the claim that the condyle and artic-
ular fossa are fundamentally not designed by nature to withstand the large resultant
forces needed by the lever model [2, 3]. Furthermore, criticisms were also raised
by researchers that the Class III lever model does not include a consideration of the
issue regarding the center of mandibular rotation [2, 4].
Moreover, observations from two studies have also raised concerns with the idea
that whether or not if there is a force at the condyle, rather than the condyle being the
mechanisms of force generation [2, 5]. The study by Roberts in 1974 postulated that
it is not possible for an additional reaction force to be present at the condyle [5]. A

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 23
A. H. Choi, Bone Remodeling and Osseointegration of Implants, Tissue Repair
and Reconstruction, https://doi.org/10.1007/978-981-99-1425-8_3
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24 3 Understanding the Biomechanics

Fig. 3.1 Mandible as a


Class III lever [1]

closed triangle can be created using vectors of the bite force together with the muscles
of masseter and temporalis, as each force can be described by a vector whose length
is equivalent to the force magnitude. In addition, since accurate and complete data on
the direction of the three forces as well as the information concerning the magnitude
of the muscle forces generated by the masseter and temporalis were unavailable,
Roberts argues that the creation of a triangle with these forces in equilibrium is
completely theoretical [5]. Likewise, the study by Roberts and Tattersall also stated
that their analysis is based on the simple assumptions that during the elevation of the
mandible, no significant force is expended at the temporomandibular joint [2].
The study by Parrington in 1934 suggested that the mandible could be considered
as a stationary beam when analyzing external forces on the mandible during masti-
cation [6]. This approach was later used in a number of studies where the internal
stresses and strains on the mandible during mastication were examined [7–10].
The study by Stern has pointed out that since under conditions of equilibrium,
the moments about any point will be equal to zero; hence, the figures regarding
the amount of force which is being applied to the dentition will be the same when
calculating moments about the center of the mandibular condyle, the center of the
chin, the instantaneous center of rotation, or any other point in space [11].
Despite the fact that it may be appropriate to examine mammalian jaws purely
in the lateral projection for bilateral molar or incisor biting, Hylander postulated
in his study in 1975 that such an analysis for unilateral biting is incomplete [12].
This is based on the idea that the projected bite point is never located in the mid-
sagittal plane, and as a result, it is beneficial to investigate the human mandible
in the frontal projection. In his later study, he determined that during mastication,
lower levels of compressive stress would act across the ipsilateral condyle, while a
large compressive reaction force will act across the contralateral mandibular condyle
during both molar biting and unilateral mastication [13]. Furthermore, the ipsilateral
condyle might even be free of stress or there may be tensile stress acting across
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3.2 Biomechanics of the Temporomandibular Joint 25

it under certain circumstances during unilateral molar biting. Additionally, the total
magnitude of force at the condyles might not be affected by the narrowing or widening
of the dental arches, but only the proportion each condyle will sustain as previously
suggested [12, 14]. The existence of condylar forces is determined by the nature of
muscle positions in the sagittal plane.

3.1.1 Hypotheses Based on Non-lever Action

Disagreement also exists regarding the legitimacy of the lever action hypothesis and
the human mandible behaving as a Class III lever. Either directly or indirectly, several
researchers have proposed that there are little or no reactive forces detected at either
of the mandibular condyle.
The first study that disagreed with the idea of lever action of human jaw mechanics
was by Wilson in the 1920, claiming that there can be no reaction force at the
mandibular condyle since the resultant force of the muscles of the masseter, medial
pterygoid, and temporalis rests perpendicular to the occlusal plane. Consequently,
the interpretation of the human mandible as a lever is incorrect [15].
The concept of non-lever action of mandibular mechanics was further reinforced
in the study by Robinson, suggesting that the resultant adductor muscle force passes
through the first molar. Hence, biting on the first molar in this projection would
indeed result in a non-lever action of the mandible, that is all the resultant muscle
force would be transmitted directly through the teeth assuming that the resultant
force has been correctly determined [3].
The study by Frank [16] also supported the non-lever action of the mandible, and
the reasons were based on radiographic analyses of the human mandibular condyle.
Frank observed in each of the radiographs that the condyle was never in direct
contact with the articular eminence. Based on these findings, it was concluded that
the mandible could not function as a lever as the condyle was not functioning as a
fulcrum.
In 1971, Gingerich proposed that the mandible performs like a link between the
bite force and the adductor muscle instead of a lever during biting, and subsequently
reinforcing the non-lever action hypothesis of the human mandible [17]. A later study
by Tattersall has also indicated that the human mandible does not function as a lever
during chewing or biting [18].

3.2 Biomechanics of the Temporomandibular Joint

As a compound joint, the function and structure of the temporomandibular joint


(TMJ) can be divided into two distinct systems:
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26 3 Understanding the Biomechanics

1. The first system centers on the tissues encapsulating the inferior synovial cavity.
The condyle-articular disk complex is the joint structure responsible for the rota-
tional movement within the TMJ. This is due to the fact that the articular disk
is attached tightly to the condyle by discal ligaments; therefore, the only physi-
ological movement that can occur between these surfaces is rotation of the disk
on the articular surface of the condyle.
2. The second system centers on the function against the surface of the mandibular
fossa and is interrelated to the condyle-articular disk complex as discussed above.
Given the articular disk is not firmly fixed to the articular fossa, free sliding
movement can occur between these surfaces in the superior cavity. This move-
ment occurs as a result of the mandible being positioned forward (translation).
Translation therefore occurs in the superior joint cavity between the superior
surface of the articular disk and the mandibular fossa.
As muscle activity increases, the condyle is forced more intensely against the
articular disk and the articular disk against the mandibular fossa. This in turn causes
an increase in the interarticular pressure of these joint structures. In essence, the
interarticular pressure is the pressure between the articular surfaces within the TMJ.
The presence of interarticular pressure is crucial as the joint will technically dislocate
and the articular surfaces will separate if there is no interarticular pressure [19]. As the
interarticular pressure increases, the condyle will position itself in the intermediate
zone as a result, and this is where the articular disk is the thinnest. Conversely, a
reduction in the interarticular pressure will cause the disk space to widen, and this
space is filled through the rotation of the articular disk to the posterior or anterior
borders. Moreover, the width of the articular disk space varies with interarticular
pressure. For instance, the disk space widens if the mandible is at the closed rest
position due to the interarticular pressure being low. On the other hand, high pressure
due to the clenching of the teeth will lead to a narrowing of the articular space.
It is also vital to gain an insight into the correlation between the activity of the
mandible and the articular disk. There is minimal elastic traction on the articular disk
when the teeth are bought together and the condyle is in the closed joint position.
During the opening movement of the mandible, the condyle is pulled forward
along the articular eminence and the force to retract the articular disk is increased.
The superior retrodiscal lamina is being pulled gradually by this opening movement.
During the protrusion of the mandible, the superior retrodiscal lamina is also involved,
and the ligament will keep the articular disk rotated as far posteriorly on the condyle
as permitted by the width of the articular space as the mandible is moved to and
returned from a full forward position.
As discussed above, four pairs of muscles make up the muscles of mastication, and
the lateral pterygoid muscle is one of those muscles. The superior lateral pterygoid
is activated only in combination with the action of the elevator muscles during the
closing movement of the mandible [19]. This is also accurate during a power stoke.
Theoretically, it can be stated that the articular disk is protracted by the superior
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References 27

lateral pterygoid, and the disk is pulled anteriorly and medially as soon as the ptery-
goid muscle is active. However, this function does not happen during mandibular
movements.
Gaining a more thorough understanding into the significance of the function of
the superior lateral pterygoid during the power stroke can be achieved by observing
the mechanics of chewing. A reduction in the interarticular pressure on the biting
side is observed once resistance is encountered such as when biting on hard food
during the closing movement of the mandible. This phenomenon takes place due to
the force of closure being applied to food instead of the joint [19].

3.3 Concluding Remarks

The shape of the mandible is designed by nature in such a way so that it can resist
any shearing or bending stress as well as preventing any fractures during functional
movements. The techniques typically used to record the biomechanical actions that
accompany the functional loading of the human mandible are highly invasive; hence,
a full and clear understanding into the events are still incomplete. In this regard,
computer modeling and simulation offer a promising alternative approach with the
added capacity to predict local stresses and strains in inaccessible positions. Mathe-
matical approaches such as finite element analysis provide unparalleled precision in
the representations of gradients, magnitudes, and directions of stresses and strains
throughout the entire mandible. The biomechanical behavior of mammalian jaw
could also be extrapolated through experimental studies, and to a certain extent,
accuracy could be offered.

References

1. Smith RJ (1978) Mandibular biomechanics and temporomandibular joint function in primates.


Am J Phys Anthropol 49:341–349
2. Roberts D, Tattersall I (1974) Skull form and the mechanics of mandibular elevation in
mammals. Am Mus Novitates 2356:1–9
3. Robinson M (1946) The temporomandibular joint: theory of reflex controlled non-lever action
of the mandible. J Am Dent Assoc 33:1260–1271
4. Grant PG (1973) Biomechanical significance of the instantaneous center of rotation: the human
temporomandibular joint. J Biomech 6:109–113
5. Roberts D (1974) The etiology of the temporomandibular joint dysfunction syndrome. Am J
Orthodont 66:498–515
6. Parrington FR (1934) On the cynodont genus galesaurus, with a note on the functional
significance of the changes in the evolution of the theriodont skull. Ann Mag Nat Hist 13:38–67
7. Hylander WL (1977) In vivo bone strain in the mandible of galago crassicaudatus. Am J Phys
Anthrop 46:309–326
8. Bock WJ, Kummer B (1968) The avian mandible as a structural grider. J Biomech 1:89–96
9. Badoux DM (1966) Statics of the mandible. Acta Morph Neerl Scand 6:251–256
10. Bock WJ (1966) An approach to the functional analysis of bill shape. Auk 83:10–51
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28 3 Understanding the Biomechanics

11. Stern JT Jr (1974) Biomechanical significance of the instantaneous center of rotation: the
human temporomandibular joint. J Biomech 7:109–110
12. Hylander WL (1975) The human mandible: lever or link? Am J Phys Anthrop 43:227–242
13. Hylander WL (1979) An experimental analysis of temporomandibular joint reaction force in
macaques. Am J Phys Anthropol 51:433–456
14. Hylander WL (1984) Stress and strain in the mandibular symphysis of primates: a test of
competing hypotheses. Am J Phys Anthropol 64:1–46
15. Wilson GH (1920) The anatomy and physics of the temporomandibular joint. J Nat Dent Assoc
7:414–420
16. Frank L (1950) Muscular influence on occlusion as shown by x-ray of the condyle. Dent Digest
56:484–488
17. Gingerich PD (1971) Functional significance of mandibular translation in vertebrate jaw
mechanics. Postilla 152:1–10
18. Tattersall I (1973) Cranial anatomy of archaeolmurinae (lemuroidea primates). Anthrop Pap
Amer Mus Nat Hist 52:1–110
19. Okeson J (1985) Fundamentals of occlusion and temporomandibular disorders. The CV Mosby
Co., USA
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Chapter 4
Mathematical Analysis of the Mandible

During mastication, a bite force is produced by combining numerous muscles acting


on the mandible at the same time. Presently, the biggest issue is defining the involve-
ment of each muscle in creating this bite force, as the conditions of static equilibrium
cannot be utilized in resolving this problem. Mastication can be defined as the process
of chewing food and the food is crushed and grounded against the mandibular and
maxillary teeth. This process is extremely complex that utilizes teeth, periodontal
supportive structure, the muscles of mastication as well as the salivary glands, cheeks,
tongue, palate, and lips.

4.1 Tooth Contact and the Biting Force

Mastication consists of a rhythmic and well-controlled opening and closing of teeth


in the mandible and the maxilla. Every opening and closing of the mandible signifies
a chewing stroke and the movement pattern of a complete chewing stroke can be
described by a tear-shaped pattern. The complete movement can be divided into an
opening and a closing phase. Furthermore, the closing phase can be further divided
into the crushing phase and the grinding phase [1].
The following sequence occurs if the mandible is traced in the frontal plane during
a single chewing stroke:
I. The mandible will drop downwards during the opening phase to a position in
which the incisal edges of the teeth are approximately 16 to 18 mm apart [2].
The mandible then moves in a lateral direction 5 to 6 mm from the midline. The
closing movement of the mandible begins at the end of this stage.
II. The closing movement can be categorized into two distinct phases: crushing
and grinding. Crushing is the first phase, and the food is trapped between the
mandibular and maxillary teeth. The grinding phase is the second phase where
the mandible is guided by the occlusal surfaces of the teeth back to the intercuspal

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 29
A. H. Choi, Bone Remodeling and Osseointegration of Implants, Tissue Repair
and Reconstruction, https://doi.org/10.1007/978-981-99-1425-8_4
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30 4 Mathematical Analysis of the Mandible

position, which causes the cuspal inclines of the teeth to pass across each other,
permitting shearing and grinding of the mass of food.
Slight anterior movement of the mandible can be observed throughout the opening
phase during a regular chewing stroke if the movement of a mandibular incisor is
drawn in the sagittal plane. The mandible on the other hand follows a somewhat
posterior trace during the closing movement, finishing in an anterior movement
returning to the starting maximum intercuspal location.
Understanding the role of tooth contacts during mastication is vital. At the begin-
ning, little contacts occur when food is introduced into the mouth. The incidence of
tooth contacts increases as the food mass is broken down. Contacts will take place
during every stroke in the final stages of mastication just before swallowing [3].
Two types of contact have been identified [4]:
1. Gliding, which occurs as the cuspal inclines pass by each other during the opening
and grinding phases of mastication, and
2. Single, which occurs in the maximum intercuspal position.
It has been noticed that around 194 ms is the average time length for tooth contact
during mastication [5]. It is apparent that these contacts influence or even dictate
the initial opening and final grinding phase of the chewing stroke based on these
observations. Data related to the quality and quantities of tooth contacts as well as
issues concerning the nature of the chewing stroke during mastication are constantly
relayed back to the central nervous system. By utilizing this feedback mechanism,
adjustments in the chewing stroke can then be carried out based on the kind of food
being chewed.
Typically, the maximum biting force that can be applied to the teeth varies between
different individuals. The study by Brekhus and co-workers described the biting load
for males vary from 53 to 64 kg while the maximum biting loads range from 35 to
44 kg for females [6]. Moreover, it has been observed that the magnitude of the
maximum biting force appears to increase with age up to the point of adolescence
[7, 8]. With exercise and practice, it has been shown that an individual can increase
their maximum biting force over a period of time [6, 8, 9].
Observations from the study by Howell and co-workers suggested that the
maximum force that can be applied to the central incisors was between 13 to 23 kg,
and the maximum force that can be applied to the first molar was 41 to 90 kg [10].
The greatest amount of force is placed on the first molar region during chewing, and
chewing mostly occurs on the first molar and second premolar area with harder foods
[11]. Subsequently, an individual consuming a diet composed of large quantities of
hard food will develop stronger biting force.

4.2 Calculating Forces at the TMJ

As previously mentioned, defining the weight of each muscle in the creation of a bite
force has been challenging, and one simple approach that has been hypothesized is
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4.2 Calculating Forces at the TMJ 31

to assume each muscle will produce a force relative to its cross-sectional area [12].
For the temporomandibular joint (TMJ), the unknowns for bilateral static bite force
would then be the magnitude of the proportionality constant and the magnitude and
direction of the reaction force at the TMJ. These can be determined by balancing the
horizontal and vertical components of the force projected onto the sagittal plane and
the moments about an axis perpendicular to the sagittal plane [13].
Contradictory results were observed during calculations of the forces acting on
the TMJ from mathematical models based on the disagreement centered on the role
of the TMJ and its possible action as a load-bearing joint in spite of the amount of
time spent by various researchers in addressing this issue [14–27]. With all vectors
determined in three-dimensions, a complete model of all the forces contributing to
the TMJ reaction force would be complex. The following information is needed to
calculate the total joint reaction force:
1. The direction and magnitude of the bite force; and
2. The lengths of the moment arms in addition to the magnitude and direction of
each muscle force.
Force transducers can be quickly used to determine the extent and direction of the bite
force, while the moment arm lengths can be established from lateral cephalograms
of human subjects [15].
Anatomical considerations such as the total cross-sections of all muscle fibers
or the physiological cross-sections as well as other physiological parameters such
as the speed of contraction, level of neuronal activation, and the muscle length will
determine the force magnitude each muscle can apply [28, 29]. The force magnitude
can be estimated based on the data available on the physiological cross-sectional
areas of various muscles (Table 4.1). The value of maximum muscle tension (┌),
a correlation between the physiological cross-sectional area of a muscle, and the
maximum force it can exert is given in Table 4.2.
Two methods have been used to calculate the magnitudes of the muscle forces. The
first approach utilizes the total cross-sectional area to estimate the force produced
by each muscle [26, 28, 29, 33, 36]. The second approach, the force of each muscle
is determined based on the integrated electromyogram (IEMG) from each muscle
(Table 4.3) [20, 28, 37].

Table 4.1 Physiological


Muscles Schumacher [29] Pruim et al. [28]
cross-sectional areas of the
muscles of mastication (cm2 ) Masseter 3.02 5.3*
[28, 29] Medial pterygoid 1.97
Lateral pterygoid 1.83 2.1
Temporalis 3.81 4.2**
Openers – 1.0***
* Includes both masseter and medial pterygoid
**Includes both anterior and posterior temporalis
***Only digastric was measured
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32 4 Mathematical Analysis of the Mandible

Table 4.2 Average maximum muscle tension (┌) in N/m2 [28, 30–35]
Author Maximum muscle tension (┌)
Pruim et al. [28] 1.4 × 106
Ikai and Fukunaga [30] 0.7 × 106
Hettinger [31] 0.4 × 106
Carlsoo [32, 33] 1.1 × 106
Morris [34] 0.9 × 106
Fick [35] 1.0 × 106

Table 4.3 Averaged calculated maximum muscle forces (N) in each single muscle group and
related standard deviations [28, 29, 32, 33, 38, 39]
Muscle Osborn and Prium et al. [28] Schumacher [29] Carlsoo [32, 33,
Baragar [38] 39]
Masseter 450 639 ± 176* 340 614 ± 107
Medial 254 190 299 ± 46
pterygoid
Lateral 382 378 ± 106 175 525
pterygoid
Temporalis 264 362 ± 65 420** 519 ± 102
(anterior)
Temporalis 323 197 ± 26 305 ± 102
(posterior)
Openers 107 115 ± 40 – –
* Masseter + Medial Pterygoid
**Anterior Temporalis + Posterior Temporalis

4.3 Barbenel’s Analysis

The first analysis of the force actions at the TMJ was presented in 1972 by Barbenel
[21]. The co-ordination system used in the study is shown in Fig. 4.1.
During the biting phase, the force system imposed on the mandible when it is
stationary comprise of the following three categories of forces:
1. Forces due to muscle action: The analyses were based on the mandible in the rest
position, with the muscles of each side acting equally. The muscle forces consid-
ered in the analysis were those produced by the masseter (F masseter ), temporalis
(F temporalis ) and the internal and external pterygoid (F Int Pterygoid and F Ext Pterygoid )
muscles (Fig. 4.2a).
2. Forces due to bite load: This load was arbitrarily considered acting equally on
each side of the mandible, with a magnitude of L and directed at an angle θ to
the y-axis. The moment of the load about the intercondylar axis:
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4.3 Barbenel’s Analysis 33

Fig. 4.1 Co-ordinate axes used in joint force analysis. The z-axis is directed inwards along the
intercondylar axis [21]

L(X cosθ − Y sinθ) (4.1)

where X and Y is the co-ordinate of the point at which the line of action of
the load intersects the occlusal plane (Figure 4.2b).
3. Force at the TMJ: The force was assumed to act at an angle of φ to the y-axis
and have a magnitude R (Fig. 4.2c).
Three equations of equilibrium for the mandible subjected to the force systems
were derived by examining moments about the intercondylar axis and applying the
determined muscle force components as shown in Table 4.4:
a. Force component in the x-direction is equal to zero:

Fig. 4.2 a Muscles considered in the analysis, b bite load parameters and c temporomandibular
joint force parameters [21]
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34 4 Mathematical Analysis of the Mandible

Table 4.4 Muscle force parameters used in Barbenel’s analysis [21]


Muscle Moment arm about intercondylar axis (cm) Force component
x-axis y-axis z-axis
Masseter 2.7 0.55 0.84 −0.12
Internal pterygoid 2.3 0.50 0.78 0.38
External pterygoid 0.0 0.91 −0.17 0.39
Temporalis 2.6 −0.46 0.84 −0.18

0.84Fmasseter + 0.84Ftemporalis + 0.77FInt Pterygoid − 0.17FExt Pterygoid


− R cosφ − L cosθ = 0 (4.2)

b. Force component in the y-direction is equal to zero:

0.55Fmasseter − 0.46Ftemporalis + 0.50FInt Pterygoid + 0.91FExt Pterygoid


− R sinφ + L sinθ = 0 (4.3)

c. Sum of the moments of the forces about any axis is equal to zero:

2.7Fmasseter + 2.6Ftemporalis + 2.3FInt Pterygoid − L(X cosθ − Y sinθ ) = 0


(4.4)

4.4 Pruim, De Jongh, Ten Bosch’s Analysis

In the 1980s, Prium and co-workers ascertained all muscle forces and the forces in
the TMJs during bilateral biting at three separate locations on the human dentition
using a mechanical approach [28]. Data on integrated electromyographic activity
(IMEG) obtained using surface electrodes to bilaterally record the electromyographic
activity in the main muscles as well as bite forces measured bilaterally through the
application of two calibrated steel transducers together with strain gauges were fed
into a calculation program as inputs in an effort to estimate these forces. It was
also stated that the activities of the lateral pterygoid muscles were not recorded in
their study. Furthermore, an agreement was also reached that the centroids of the
mandibular condyle will be the origins of an x- and y-axis system in which the x-axis
was oriented parallel to the mandibular occlusal plane, thus to the bite plane in their
experimental set-up (Fig. 4.3).
In their study, a number of assumptions were necessary:
1. A single vector can be used to signify the combined forces of the masseter
and medial pterygoid muscles. The lateral pterygoid muscle acts in a direction
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4.4 Pruim, De Jongh, Ten Bosch’s Analysis 35

Fig. 4.3 Mathematical


model based on the mandible
[28]. (M. + M. P.) Masseter
+ medial pterygoid; (B) bite
force; (A. T.) anterior
temporalis; (P. T.) posterior
temporalis; (L. P.) lateral
pterygoid; (O) opener; (J. R.)
joint reaction force

parallel to the occlusal plane and consequently, the force the muscle produced
has no y-component.
2. Forces exerted by contracting muscles can be represented by vectors and the
direction of these vectors can be defined by the connecting lines between the
centroids of the origins and the insertions of the muscles.
3. The EMG activity of the masseter is also representative for the medial pterygoid
muscle. The activity in the floor of the mouth is illustrative for the mouth openers.
There exists a muscle independent value ┌ (in N/m2 ) for each experimental
subject, which correlates the maximum force a muscle can exert (F m(max) ) and the
physiological cross-section of the muscle φm (in m2 ) as described in Eq. 4.5:

Fm(max) = ┌ · φm (4.5)

The values of the physiological cross-section of muscles for male subjects corre-
spond to the values for test subjects as determined by Schumacher [29] and are given
in Table 4.5.
During isometric contraction, the force a muscle can exert (F m ) is directly propor-
tional to the IEMG. Hence, Eq. 4.6 can be used to express the correlation between
IEMG and muscle force:
( )
IEMGm(actual)
Fm = · Fm(max) (4.6)
IEMGm(max)
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36 4 Mathematical Analysis of the Mandible

Table 4.5 Physiological


Muscles Schumacher [29] Pruim et al. [28]
cross-sections of the muscles
(cm2 ) [28, 29] Masseter 3.4 5.3*
Medial pterygoid 1.9
Anterior temporalis 4.2 2.6
Posterior temporalis 4.2 1.6
Openers – 1.0
* Includes both masseter and medial pterygoid

where IEMGm(max) is the maximum value of IEMGm of a single muscle ever recorded
during a complete experimental session from a pair of electrodes.
To calculate all forces, the laws of static equilibriums were used:
a. When the moments are referred to the origin and Eq. 4.6 is used, a new equation
is derived:
∑ ( IEMGm(actual) )
┌ · φm · am + Fb · ab = 0 (4.7)
muscles
IEMGm(max)

Values of IEMGm and the sum of both left and right bite forces (F b ) were
obtained for each bite, and the muscle and bite force lever arms (am and ab ,
respectively) were obtained from the cephalometric data. For each bite, ┌ was
determined using Eq. 4.7 along with the data on the physiological cross-sections
of muscles (φ) from Table 4.5. All forces in the elevator and antagonistic muscles
during that bite were calculated after substituting the value of ┌ in Eq. 4.5.
b. The sum of the moments = 0

Fm · am + Fb · ab = 0 (4.8)

c. The sum of the x-component = 0



Fm · cos αm + F j · cos α j + F p = 0 (4.9)
muscles

d. The sum of the y-component = 0



Fm · sin αm + F j · sin α j − Fb = 0 (4.10)
muscles
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4.5 Throckmorton and Throckmorton’s Analysis 37

4.5 Throckmorton and Throckmorton’s Analysis

In the study by Throckmorton and Throckmorton [13], the magnitude of the total
joint reaction force (F TMJ ) and its direction (φ) were determined using a 2-D model
as shown in Fig. 4.4.
The laws of statics were used to determine the magnitude and direction of the
TMJ reaction force in two stages. The sum of all moments is zero and the sum of all
forces is zero in static equilibrium. The first step is to determine the magnitude of
the muscle forces from the sum of the moments:

F(t) · a + F(m) · b + F(B) · c = 0 (4.11)

where F (t) , F (m) , and F (B) are the forces exerted by the temporalis, masseter, and bite
force, respectively (Fig. 4.4).
Determining the perpendicular distance between the muscle vector and the center
of joint rotation is the most widely used approach to calculate the moment of the
jaw muscles. The moment of a particular muscle is derived from multiplying the
measured perpendicular distance with the magnitude of the muscle force vector.

Fig. 4.4 Schematic of the 2-D model used by Throckmorton and Throckmorton to determine the
total joint reaction force [13]. F (t) is the temporalis muscle force; F (m) is the masseter muscle force;
F (mB) is the molar bite force; F (iB) is the incisor bite force; F (TMJ) is the total joint reaction forces;
(a) is the moment arm for the temporalis muscle; (b) is the moment arm for the masseter muscle
force; (c) is the moment arm for the bite force; (θt ) is the angle with the occlusal plane for the
temporalis muscle force; (θm ) is the angle with the occlusal plane for the masseter muscle force;
(θB ) is the angle with the occlusal plane for the bite forces; (φ) is the angle of the total joint reaction
force with the moment arm line (MAL)
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38 4 Mathematical Analysis of the Mandible

Another method is to separate each muscle force into components which are
perpendicular and parallel to a line passing through the center of joint rotation and
parallel to the occlusal plane. This line is known as the moment arm line (MAL)
and is shown in Fig. 4.4. Only the force components that are perpendicular to the
moment arm line generate a moment, and the length of the moment arm is determined
by measuring the distance between the muscle force vector and the center of joint
rotation (Fig. 4.4).
Consequently, Eq. 4.11 can be further expanded:

F(t) · sin θt · a + F(m) · sin θm · b + F(B) · sin θB · c = 0 (4.12)

Even though the magnitude of the forces exerted by the masseter and temporalis
muscles cannot be measured directly, the magnitude of one muscle force can be
expressed in terms of the other if the relative magnitudes of the muscle forces are
estimated:

F(m) = K · F(t) (4.13)

where K is a proportionality constant between the forces exerted by the masseter and
temporalis.
The magnitudes of the forces exerted by the masseter and temporalis can now be
determined by substituting the relative muscles forces into Eq. 4.12:
[ ]
F(B) · sin θB · c
F(m) = (4.14)
K · sin θt · a + sin θm · b

Using Eq. 4.13, the value of F (t) can finally be calculated.


Once the magnitude of each muscle force is calculated, the reaction force at the
TMJ (F (TMJ) ) can be determined using the sum of forces:

F(m) + F(t) − F(B) − F(T M J ) = 0 (4.15)

Each force is separated into horizontal components of force which are parallel to
the MAL, and vertical components of force which are perpendicular to the MAL.
Furthermore, the horizontal components of force produce translation and the vertical
components of force generate rotation [40]:
a. For the horizontal component of the reaction force at the TMJ (F (H.TMJ) ):

F(H.TMJ) = F(m) · cos θm + F(t) · cos θt − F(B) · cos θB (4.16)

b. For the vertical component of the reaction force at the TMJ (F (V.TMJ) ):

F(V.TMJ) = F(m) · sin θm + F(t) · sin θt − F(B) · sin θB (4.17)


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References 39

c. Total joint reaction force (F (TMJ) ) and its direction φ:


/
F(TMJ) = 2
F(H.TMJ) + F(V.TMJ)
2
(4.18)

F(V.TMJ)
∅ = Ar c sin (4.19)
F(TMJ)

4.6 Concluding Remarks

Different approaches have been developed focusing on how to characterize the


actions of the human mandible, all of which had to contend with the major obstacle
that stress must be deduced by other means, and it is not something that can be directly
measured. Free-body diagrams offer vectorial description of suggested external loads
during mastication, and this in turn allows for a rough estimation of the nature of
internal forces acting within the mandible. However, with this type of approach, any
thorough examination of stress distribution might prove to be problematic. They are
still useful when attempting to interpret results from theoretical and experimental
studies as they might aid in the identification of how different external forces and
moments interact to generate internal stresses.

References

1. Okeson J (1985) Fundamentals of occlusion and temporomandibular disorders. The CV Mosby


Co., USA
2. Hildebrand GY (1931) Studies in the masticatory movements of the lower jaw. Walter De
Gruyter, Berlin
3. Adams SH, Zander HA (1964) Functional tooth contacts in lateral and centric occlusion. J Am
Dent Assoc 69:465
4. Glickman I, Pameijer JHN, Roeber FW et al (1969) Functional occlusion as revealed by
miniaturized radio transmitters. Dent Clin North Am 13:667
5. Suit SR, Gibbs CH, Beng ST (1975) Study of gliding tooth contacts during mastication. J
Periodontol 47:331
6. Brekhus PH, Armstrong WD, Simon WJ (1941) Stimulation of the muscles of mastication. J
Dent Res 20:87
7. Garner LD, Kotwal NS (1973) Correlation study of incisive biting forces with age, sex, and
anterior occlusion. J Dent Res 52:698
8. Worner HK, Anderson MN (1944) Biting force measurements in children. Aust Dent J 48:1
9. Worner HK (1939) Gnathodynamics: the measurements of biting force with a new design of
gnathodynamometer. Dent J Aust 43:381
10. Howell AH, Manly RS (1948) An electronic strain gauge for measuring oral forces. J Dent Res
27:705
11. Brudevold F (1951) A basic study of the chewing forces of a denture wearer. J Am Dent Assoc
43:45
12. Amis AA, Dowson D, Wright V (1980) Elbow joint force predictions for some strenuous
isometric actions. J Biomech 13:765–775
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40 4 Mathematical Analysis of the Mandible

13. Throckmorton GS, Throckmorton LS (1985) Quantitative calculations of temporomandibular


joint reaction forces—I. the importance of the magnitude of the jaw muscle forces. J Biomech
18:445–452
14. Hylander WL (1979) An experimental analysis of temporomandibular joint reaction force in
macaques. Am J Phys Anthropol 51:433–456
15. Hylander WL (1978) Incisal bite force direction in humans and the functional significance of
mammalian mandibular translation. Am J Phys Anthropol 48:1–7
16. Hylander WL (1975) The human mandible: lever or link? Am J Phys Anthrop 43:227–242
17. Smith RJ (1978) Mandibular biomechanics and temporomandibular joint function in primates.
Am J Phys Anthropol 49:341–349
18. Roberts D (1974) The etiology of the temporomandibular joint dysfunction syndrome. Am J
Orthodont 66:498–515
19. Roberts D, Tattersall I (1974) Skull form and the mechanics of mandibular elevation in
mammals. Am Mus Novitates 2356:1–9
20. Barbenel JC (1974) The mechanics of the temporomandibular joint: A theoretical and
electromyographical study. J Oral Rehabil 1:19–27
21. Barbenel JC (1972) The biomechanics of the temporomandibular joint: a theoretical study. J
Biomech 5:251–256
22. Gingerich PD (1971) Functional significance of mandibular translation in vertebrate jaw
mechanics. Postilla 152:1–10
23. Roydhouse RH (1955) The temporomandibular joint: Upward force of the condyles on the
cranium. J Am Dent Assoc 50:166–172
24. Craddock FW (1951) A review of Costen’s syndrome. Br Dent J 91:199–204
25. Robinson M (1946) The temporomandibular joint: theory of reflex controlled non-lever action
of the mandible. J Am Dent Assoc 33:1260–1271
26. Gysi A (1921) Studies on the leverage problem of the mandible. Dent Digest 27;74–84, 184–
190, 203–208
27. Wilson GH (1920) The anatomy and physics of the temporomandibular joint. J Nat Dent Assoc
7:414–420
28. Pruim GJ, de Jongh HJ, ten Bosch JJ (1980) Forces acting on the mandible during bilateral
static bite at different bite force levels. J Biomech 13:755–763
29. Schumacher GH (1961) Funktionelle Morphologie der Kinnmuskulatur VEB. Gustav Fischer,
Jena
30. Ikai M, Fukunaga T (1968) Calculation of muscle strength per unit cross-sectional area of
human muscle by means of ultrasonic measurement. Int Z Agnew Physiol 26:26–32
31. Hettinger T (1961) Physiology of strength. Charles C. Thomas, Illinois
32. Carlsoo S (1958) Motor units and action potentials in masticatory muscles. Acta Morph Neel
Scand 2:13–19
33. Carlsoo S (1952) Nervous co-ordination and mechanical function of the mandibular elevators.
an EMG study of the activity, and an anatomic analysis of the mechanics of the muscles. Acta
Odont Scand 10:Suppl. 1–132
34. Morris CB (1948) The measurement of the strength of muscle relative to the cross-section. Res
Q Am Assoc Hlth Phys Educ 19:295–303
35. Fick H (1904) Handbuch der Anatomie und Mechanik der Gelenke. Gustav Fisher, Jena
36. Mainland D, Hiltz JE (1934) Forces exerted on the human mandible by the muscles of
mastication. J Dent Res 14:107–124
37. Pruim GJ, ten Bosch JJ, de Jongh HJ (1978) Jaw muscle EMG-activity and static loading of
the mandible. J Biomech 11:389–395
38. Osborn JW, Baragar FA (1985) Predicted pattern of human muscle activity during clenching
derived from a computer assisted model: symmetric vertical bite forces. J Biomech 18:599–612
39. Carlsoo S (1956) An electromyographic study of the activity, and an anatomic analysis of the
mechanics of the lateral pterygoid muscle. Acta Anat 26:339–351
40. Bock WJ (1968) Mechanics of one- and two-joint muscles. Am Mus Novit 2319:1–45
www.dentalbooks.co

Chapter 5
Understanding Bone Structures

Within the human body, bone is responsible for a number of functions including
synthetic functions (production of blood cells), metabolic functions (fat storage,
mineral storage and balance, and regulation of calcium and phosphate ions), and
mechanical functions (under functional loadings). Numerous experimental investi-
gations have been conducted to determine the elastic properties of human bones, and
one of the key findings from these experiments is that the mechanical properties of
bone will differ based on the orientation and position of the specimen; simply, bone
is both anisotropic and heterogeneous in its mechanical properties. Given the fact
that bone is an anisotropic and heterogeneous material, experimental results will be
governed by the anatomical location of the specimen.
A pivotal role is also played by the parameters or settings used during experimen-
tations such as the duration of load and deformation rate in mechanical tests, or the
vibration frequency in ultrasonic tests. The use of ultrasonic waves is well-established
in determining the elastic properties of bone. A recent study has hypothesized that
there is a clinical potential for ultrasounds to measure bone properties in different
populations, i.e., between adult and juvenile groups [1]. The elastic properties are
determined based on the velocity measurements of shear and longitudinal waves
propagating in certain directions in the bone sample if the elastic anisotropy and
density of bone are stated.
Properties and features of bone will also change based on the type of bone as well
as biological factors such as age, the extent of pathological degradation, and level of
activity of the living bone. Variations in these features along with the preservation
conditions of the specimen until it is used for experimentation all contribute to an
irregular distribution of its mechanical properties [2, 3].
Bone occurs in two forms from a macroscopic point of view, and most bones in
the human body have both types: the dense compact (cortical) bone forming an outer
shell that surrounds a core of spongy cancellous bone. Both types consisted of one-
third organic and two-thirds inorganic materials. The inorganic portions are mainly
calcium phosphate and calcium carbonate, while the organic portions consist of
cells. There are three types of cells that make up the organic component: osteoblasts,

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 41
A. H. Choi, Bone Remodeling and Osseointegration of Implants, Tissue Repair
and Reconstruction, https://doi.org/10.1007/978-981-99-1425-8_5
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42 5 Understanding Bone Structures

which are generally thought of as the cells responsible for bone formation; osteo-
clasts, which form the matrix and are also responsible for bone demineralization;
and the fibroblasts are responsible for the formation of collagenous fibers. Both the
osteoblasts and osteoclasts are imprisoned within the “Haversian” and surrounding
network, and it has been suggested that these cells may act as site-specific activators
and regulators controlling the creation of more bone tissues [4, 5].
Observations from scanning electron microscopy studies revealed the sizes and
distribution of the mineral and organic phases within the cortical bone that begins at
the elemental level (less than 0.005 μm) and microstructural level (between 1 and
10 μm) will impact the mechanical characteristics of cortical bone [6]. A relationship
exists between the mineral fraction and the mechanical properties of cortical bone
[7–10]. Tiny changes in the mineral fraction will result in a significant change in
the material properties. The mechanical behavior of cortical bone at the next level
in the hierarchy (between 10 and 50 μm) can be ascertained from microhardness
examination [11], which measure the physical effects of small-scale changes in the
mineral content of the bone [12].
As mentioned earlier, nanoindentation has been used to investigate the properties
of hard tissues such as bone since the 1990s [13–22]. Measuring the mechanical
properties such as Young’s modulus and hardness at the surface of a material can
be achieved through the use of this technique. The procedure for nanoindentation
is much simpler particularly for small complex-shaped samples such as enamel,
cementum, and dentine compared to other conventional mechanical examinations
such as tensile testing [23]. Above all, nanoindentation allows the measurement of
mechanical properties in a very small selected area within the specimen where the
dimensions may be at a micrometer or even nanometer scale. This is particularly
important when measuring local properties of non-homogeneous structures such as
dental calcified tissues.
Typically, the properties of mandibular cortical bone are deduced in three orthog-
onal directions relative to the surface of each sample: longitudinal (axial along the
bone surface), radial (normal or perpendicular to the bone surface), and tangential
(supero-inferior along the bone surface) (Fig. 5.1). A limitation of the loading exper-
iments is that loading could not be carried out in the radial direction due to the
overall thickness of the cortical bone in this direction. Hence, the yield stresses and
elastic constants were estimated for the radial direction from the data obtained in the
tangential direction (Table 2.1) [24, 25].
A number of studies have suggested that the cortical bone of the mandible is stiffer
in the longitudinal than in the tangential and radial directions, indicating anisotropic
behavior [24–28]. The average elastic moduli in the tangential and radial directions
are approximately 40–70% of those along the longitudinal direction [21]. More
importantly, the values of elastic moduli in the tangential and radial directions are
roughly the same, and as a result, the cortical bone of the mandible can be considered
transversely isotropic, with a greater Young’s modulus in the longitudinal direction
and a lower Young’s modulus in all transverse directions. The strength of the mandible
is also higher in the longitudinal direction than in transverse directions (Table 2.1).
Similarly, the study by O’Mahony et al. also suggested that a model of transverse
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5 Understanding Bone Structures 43

Fig. 5.1 Definition of directions

isotropy for the mandibular cancellous bone [29]. They observed Young’s modulus
in the infero-superior direction was less than the bucco-lingual and mesio-distal
directions, and the difference between the mesio-distal and bucco-lingual directions
was negligible, indicating the symmetry axis is along the infero-superior (weakest)
direction.
Of vital significance is the constitutive properties of cancellous or trabecular bone
as it is this bone that is in direct contact with the implant or prosthesis. Given that
cancellous bone is a cellular material consisted of a connected network of rods or
plates where a network of rods produces open cells and a network or plates creates
closed cells, its mechanical behavior is typical of a cellular material. The stress–
strain curve of such materials has three distinct regimes of behavior. The compressive
behavior in the first regime is linear elastic as the cell walls bend or compress axially,
and eventually, the cells start to collapse at high enough loads via elastic buckling,
which also leads to brittle fracture or plastic yielding of the cell walls. This second
phase of collapse progresses at a roughly constant load until the cell walls meet
and touch. Once this happens, the resistance to load increases, giving rise to a final
increasingly steep portion of the stress–strain curve (Fig. 5.2) [30].
The direction of the applied loads will govern the symmetry of the structure in
cancellous bone. For instance, the trabeculae often develop a columnar structure
with cylindrical symmetry in bone where the loading is primarily uniaxial such as
the vertebrae. However, if the stress pattern in the cancellous bone is complex, then
the structure of the network of trabeculae is also complex and highly asymmetric [31,
32]. It has been proven both theoretically and experimentally that Young’s modulus
of cancellous bone is strongly dependent on the bone’s structure density or some-
times referred to as apparent density [33–38]. Cancellous bone has a structure with
distinctive textural anisotropy in many areas within the skeleton and subsequently
cannot be adequately predicted by a single scalar measure such as structural density.
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44 5 Understanding Bone Structures

Fig. 5.2 Compressive


behavior of a stress–strain
curve for cancellous bone.
According to the study by
Hayes and Carter [30],
Young’s modulus and
compressive strength
increase as the relative
density increases ((1)
apparent density = 962
gm/cc; (2) apparent density
= 697 gm/cc; and (c)
apparent density = 559
gm/cc) (Modified and
adapted from [30])

The elastic constants of cancellous bone in such instances depend upon its textural
anisotropy in addition to its structural density.
Even though the elastic moduli and yield strength ascertained in the studies by
Arendts and Sigolotto displayed regional variation (up to a factor of one and a half
times between minimum and maximum values), their values did not indicate system-
atic differences between particular locations of the mandible such as lower margin
vs. upper margin or ramus vs. corpus [24, 25]. Conversely, a later study by Dechow
et al. revealed the stiffest region of the mandibular corpus is at the lower border
inferior to the canine, suggesting that this region has the highest resistance to torsion
and is the region in which torsional stresses are believed to change during function
[39]. Furthermore, additional data from two other studies indicated that [40, 41]:
I. An increase in the longitudinal Young’s modulus going from the molar region
to the symphysis,
II. The lingual cortex is stiffer than the buccal cortex in the symphysis and premolar
regions, and
III. The cortical bone is stiffer at the lower border of the corpus than at the alveolus.
In comparison with the molar region in the body of the mandible, a greater longi-
tudinal Young’s modulus at the symphysis may compensate for the anticipated higher
torsional loadings experienced in that area. This hypothesis was reinforced by the
findings on apparent density and mineralization density, revealing that the areas of
the highest density are located at the symphysis [42, 43].

5.1 Bone Healing Process

The process of bone healing is well-coordinated and complex. Once a fracture occurs,
bone begins healing indirectly through the formation of callus or directly through
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5.1 Bone Healing Process 45

Fig. 5.3 Stages of bone healing process. a Hematoma formation, b Fibrocartilaginous callus forma-
tion, c Bony callus formation, d Bone remodeling. Modified and adapted with permission from [46]
(http://creativecommons.org/licenses/by/4.0/)

bone union. As healing progresses, cartilaginous callus or soft callus is created


through the activities of endothelial and skeletal cells that bridge the gap between
the bone fragments. Soft callus then develops into hard callus (Fig. 5.3) [44, 45].
Intramembranous and endochondral ossification are two typical mechanisms of
bone formation [47, 48]. Cartilage is formed during endochondral ossification when
mesenchymal stem cells (MSCs) are differentiated into chondrocytes and will even-
tually be replaced by bone. On the other hand, bone tissue in intramembranous
ossification is produced directly by osteoblasts created through the differentiation of
MSCs [44, 48, 49].
Bone healing can be categorized into both primary bone healing and secondary
bone healing. If the bony fragments are firmly united under compression from implan-
tation, then primary bone healing will take place and the two fragments are joined
and healed directly through the activities of osteoclasts and osteoblasts. More impor-
tantly, there is no formation of callus [44, 45, 50]. The most common category of
bone healing is secondary bone healing and this occurs if there is a small quantity of
motion in the fracture site. Formation of soft callus is the result of interfragmentary
motion, leading to secondary bone formation through both intramembranous and
endochondral ossification [45, 51].
Osteoblasts, osteocytes, osteoclasts, and osteoprogenitor bone cells (osteogenic
and develop into osteoblast cells) are the four most important cells in this bone
healing process, which together are recognized as the basic multicellular unit (BMU)
involved in bone regeneration [52, 53].
The osteoblasts are responsible for the production of bone matrix constituents and
are found in clusters along the bone surface, “coating” the layer of bone matrix they
are creating [54]. The origin of the osteoblast cells can be traced back to multipotent
MSCs, which has the capacity to separate into osteoblasts as well as into myoblasts,
adipocytes, fibroblasts, and chondrocytes [54, 55]. Conversely, osteoclast cells are
responsible for bone resorption and they are derived from hematopoietic cells of
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46 5 Understanding Bone Structures

the mononuclear lineage and are giant multinucleated cells with a diameter of up to
100 nm [56].
The term basic multicellular unit is frequently used to describe the close collabo-
rative efforts of osteoblasts and osteoclasts in the remodeling process. Bone forma-
tion and bone resorption are balanced in a homeostatic equilibrium. On a cellular
level, the simultaneous biological and mechanical actions play a critical role in the
delicate equilibrium between bone formation, growth, and resorption. Moreover,
the combined efforts of osteoblasts and osteoclasts also played a part in the bone
remodeling of defects such as microfractures [57, 58].
The clinical evaluation of fracture healing involves a number of stages, and the
complete process can be assessed using an assortment of testing methods such as
histology, mechanical tests, radiographic inspections, and computerized tomography
(CT) scans [59]. The mechanical properties of bone undergoing the healing process
can be evaluated using testing methods such as torsion, tensile compression, or flexure
[60, 61]. Torsion and four-point-bending tests are the most ideal for assessing the
mechanical function of a healing bone and in particular for long bones. Normally,
torsion test is a more suitable approach as the same amount of torque is applied
across the entire cross-sectional area of the callus. Moreover, the test provides a
more realistic simulation of orthopedic surgical procedures. On the other hand, a
non-uniform bending moment might be generated throughout the callus by four-
point bending [62]. Precautions must also be taken if three-point bending tests are
used to evaluate the mechanical properties of a healing bone, especially during the
early stages of the healing process. This is due to concerns arising from the site
where the force is applied might be situated at the original fracture spot, and at these
early stages of healing, the new bone tissue is mainly composed of cartilage, calcified
cartilage, or less mature bone tissue depending on how far the healing has progressed
[62].
Histological analysis as well as radiographic inspections can be used if neces-
sary to assess biological repairs. In 2001, it was suggested that acoustic emission
could be utilized as a non-destructive method for monitoring fracture healing [63].
In their study, acoustic emission was used to monitor the yield strength of healing
callus during external fixation in 35 patients [64]. The most common radiographic
investigations of fracture healing involve the bridging of fracture site by callus, oblit-
eration of the fracture line, and continuity. At the moment, 3-D CT scan reconstructed
images or microtomography can be used in research projects to determine the volume
of callus [65].
It has been suggested that there is a necessity to quantitatively and non-invasively
estimate the quality and strength of fracture callus during bone healing in an effort
to determine the effectiveness of certain treatments and that bone strength could be
predicted using a patient/specimen-specific finite element (FE) model created using
CT scans to compensate for the inability to measure quantitatively the bone strength
in the fracture healing process in clinical settings. Moreover, the prediction of callus
strength using the FE approach would enable an objective treatment plan [66, 67].
The study by Shefelbine et al. suggested that the mechanical properties of fracture
callus could be estimated using micro-CT scan data and FE modeling [67]. Later,
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5.1 Bone Healing Process 47

using New Zealand white rabbits where a 10 mm long bone defect was created
in the central femur, a relationship was developed by Suzuki et al. that converts
bone density measured by quantitative CT scans to Young’s modulus. A specimen-
specific FE model was generated based on CT data after the femur was removed
after 3, 4, and 5 weeks, and mechanical testing was carried out at the same time.
Based on their findings, they suggested that the bone strength could be quantitatively
predicted during the bone healing process by finite element modeling (FEM) using
appropriate equations that convert data from CT scans to material properties [66].
Such CT scan-material properties relationships will be discussed in details in the
patient-specific modeling chapter.
Compared to CT scans, bone histology is an invasive approach used in the clinical
environment to investigate the bone structure during fracture healing. Tissue hetero-
geneity within callus is not fully captured in a majority of healing studies that involve
animal trials as well as compared to single longitudinal sections of a healing fracture.
Consequently, transverse sections at the fracture line level can offer the most accurate
measurement of cross-sectional area in addition to an estimation of tissue hetero-
geneity [68]. Concerning callus cross-section, bone tissue, and fibrous cartilage can
be represented as the percentage of the total cross-sectional callus area [68]. Bone
metabolism can be examined by staining both osteoblasts and osteoclasts, and their
activities can then be quantified. Furthermore, bone formation-related factors can
be assessed using fluorochromes and these can be utilized to assess and determine
bone remodeling and stress shielding particularly during the middle and final stages
of fracture healing [69]. In animal trials, calcein can be injected before the animals
such as rats or mice are sacrificed typically at 2, 4, 6, and 16 weeks after femoral
osteotomy. Linear calcein labeling indicated lamellar bone formation during callus
remodeling.
Fracture healing is a regenerative bone healing process where bone is repaired
without the formation of any scar tissue. The healing sequence begins with a cycle
of inflammation, cell migration, proliferation, and differentiation of progenitors into
mature osteoblasts and osteoclasts under certain biomechanical factors and remod-
eling [46]. Immune cells infiltrate into the hematoma during the bone healing process.
This triggers the release of cytokines and thus causes inflammation [44]. It has long
been considered that the immune system is vital in the healing of bone fractures
given that inflammation goes before bone regeneration. Clinicians have reported that
there is a delay in bone healing in patients treated with immunosuppressants, and the
occurrence of non-union is more frequent in certain immune-deficient patients.
It has been well-proven that bone healing begins with an inflammatory reaction
that set off the regenerative healing process and ultimately results in the reconsti-
tution of bone. During this initial period of bone healing, an unbalanced immune
reaction has been postulated to disturb the healing cascade in a way that delays
the bone healing process. The immune cell composition and expression pattern
of angiogenic factors can be examined using a sheep bone osteotomy model and
compared to a mechanically induced delayed/impaired bone healing group [70]. It
has been suggested that significantly high T cell percentages were present in the bone
hematoma in the delayed healing and the bone marrow adjacent to the osteotomy
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48 5 Understanding Bone Structures

Fig. 5.4 Bone healing and remodeling sequence. Modified and adapted with permission from [71]
(http://creativecommons.org/licenses/by/4.0/)

gap in comparison to the normal healing bone. Moreover, this was reflected in the
higher cytotoxic T cell percentage discovered under delayed bone healing conditions
signifying longer pro-inflammatory process. It has also been reported that the highly
activated periosteum adjourning the osteotomy gap displayed lower expression of
hematopoietic stem cell markers and angiogenic factors such as vascular endothelial
growth factor and heme oxygenase. This indicates that a deferred revascularization
of the injured area as a result of ongoing pro-inflammatory processes in the delayed
healing in bone fractures [70]. Observations from a number of studies also revealed
that there are unfavorable immune cells and factors contributing in the initial healing
phase (Fig. 5.4) [71].
Observations from the study by Könnecke and co-workers in which the healing
of femoral fractures in mice was analyzed using confocal microscopy revealed that
immune cells are discovered only in the endosteal region near the fractured bone
segments and edges during the formation of soft callus [72]. It was also discovered
that T and B cells were absent in the avascular cartilage filling the fracture callus. In
areas of newly formed woven bone, T and B cells reappear in the callus upon subse-
quent hypertrophy of the cartilage and the region was revascularized. The presence
of large quantities of T and B cells recorded during the bone growth and remodeling
process correlates with the increasing numbers of osteoblasts and osteoclasts in the
vicinity of newly formed bone.
Reaction of the regional lymphoid tissue, lymphatics, and lymph nodes takes place
after tissue damage via mechanical injury and inflammation. Clinical studies have
shown that closed fractures of a lower limb triggered reaction of the local lymphoid
tissue. Lymphatics were dilated draining the site of the fracture and enlargement
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5.2 Fracture Healing and Numerical Simulation 49

of inguinal lymph nodes. Furthermore, these changes continued even after clinical
healing of the fracture. On the other hand, the draining lymphatics became obliterated
and the lymph nodes disappeared in the long-lasting non-healing fractures [73–75].
Changes in iliac and popliteal lymph nodes draining lymph in rats were examined
from the region of tibial fracture and adjacent soft tissue injury [75]. Observations
displayed a reaction of local lymph nodes to internal wounds took place through
mobilization of cells from the blood circulation accompanied by activation of cellular
subsets. The authors of the study also stated that the absence of major changes in
the frequency of lymph node cell subpopulation indicated that lymph nodes are
constitutively prepared for influx of antigens from damaged tissues and only react
with increases in cell number and cell activation. The fracture gap tissue was assumed
to be the leading source of signals to the lymph nodes, releasing cellular and humoral
regulatory factors [74]. Later, the existence of a functional axis was hypothesized
between the local lymphatic (immune) system and injuries to bone and surrounding
soft tissue, suggesting that fast healing is controlled by influx into the wound of lymph
node regulatory cells while prolonged healing resulted in gradual exhaustion of the
regional lymph node functional elements and reciprocally impairment in sending
regulatory cells to the fracture gap [73].
In the context of bone fracture healing, B cells are recognized to increase at the
injury site and in the peripheral blood [72, 76]. It has been suggested that a portion of
B cells suppresses excessive and/or prolonged inflammation. The functions of other
B cells subsets in bone regeneration remain largely unclear and further investigations
are essential.

5.2 Fracture Healing and Numerical Simulation

Maintaining the integrity of the skeleton has been accepted as the principle behind
the bone remodeling sequence. The bone remodeling sequence consisted of three
consecutive phases: resorption, reversal, and formation. The resorption phase begins
with the creation of multinucleated osteoclasts as a result of partially differentiated
mononuclear pre-osteoclasts migrating to the bone surface. The commencement of
the reversal phase is marked by the appearance of mononuclear cells on the bone
surface in addition to the initiation of osteoclastic resorption. Signals for the differen-
tiation and migration of osteoblasts and the creation of surfaces for new osteoblasts
to begin bone formation are provided by mononuclear cells. The formation phase is
the final stage and it occurs when the new bone deposited by osteoblasts completely
replaces the resorbed bone. Flattened lining cells over the entire surface once the
formation phase are completed. A prolonged resting period will take place until the
beginning of a new remodeling sequence [54].
In determining the ideal mechanical-based treatment or reconstruction after an
accident or illness, the use of numerical models to simulate the process of fracture
healing may prove to be advantageous. Numerical simulation using finite element
analysis (FEA) to predict the fracture healing process has been previously reported
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50 5 Understanding Bone Structures

with the prediction validated to a certain extent utilizing the experimental works
of Claes et al. on sheep models [77, 78]. A FE model of a fracture callus was
used by Lacroix and Prendergast to simulate the time course of tissue differentia-
tion during fracture healing. Their simulation began with granulation tissue (post-
inflammation phase) and ended with bone resorption. The biomechanical regulatory
model assumed that the combination of fluid flow acting within the tissue and shear
strain governed tissue differentiation. Low fluid flows and shear strain stimulated the
formation of cartilage and ossification at even lower levels. On the contrary, high
fluid flows and shear strain stimulated the formation of fibrous connective tissue
based on the assumption that at high levels, the precursor cells are deformed. The
appearance and disappearance of various tissues found in a callus were similar to
histological observation when their mechano-regulatory scheme was examined by
simulating healing in fractures with different loading magnitudes and gap sizes [79].
Later, the influence of mechanical stimuli on cellular processes (proliferation,
migration, and differentiation) that occurred during fracture healing was attempted
in the study by Gómez-Benito and co-workers. The model, on the basis of these three
processes, then simulated the evolution of geometry, distributions of cell types, and
elastic properties inside a healing fracture. The three processes were implemented in
a FE code as a combination of three coupled analysis stages (a biphasic, a diffusion,
and a thermoelastic step). The callus geometry, tissue differentiation patterns, and
fracture stiffness predicted by the model were similar to experimental observations
when the healing patterns of fractures with different mechanical stimuli and different
gap sizes were analyzed [80].
Ghiasi et al. theorized that the initial phase of healing has a contributory
mechanobiological effect on the overall bone healing process, resulting in the creation
of an initial callus with an ideal range of material properties and geometry to achieve
the most efficient healing time [81]. Using the FE model by Lacroix and Pren-
dergast [79], Ghiasi and co-workers simulated the bone healing process in models
with different diffusion co-efficients of MSC migration, granulation tissue Young’s
moduli, callus geometries, and interfragmentary gap sizes, as these parameters modu-
late the outcome of bone healing during its initial phase, which involves inflammatory
stage, hematoma evolution to form granulation tissue and initial callus development
during the first few days post-fracture. Their results suggested that how the speed of
MSC migration, stiffer granulation tissue, thicker callus, and smaller interfragmen-
tary gap improved healing to some degree but a state of saturation was reached after
a certain threshold.
A number of studies have been carried out to model and simulate the course
of healing under various loading conditions and mechanical stimulations. In 2008,
Prendergast and co-workers proposed the development of a tissue differential model
for fracture healing that could be applied in complicated 3-D geometries and loading
condition as well as being capable of capturing the influence of the mechanical envi-
ronment on the number of cellular and tissue processes. Poroelastic FEA was used in
their study so that the effect of the frequency of dynamic loading could be modeled.
According to the authors, their model predicted that asymmetric loading generated an
asymmetric distribution of tissues in the callus but only for high bending moments. In
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5.2 Fracture Healing and Numerical Simulation 51

addition, the frequency of loading was also predicted to have an effect [82]. The same
group later postulated that computational simulations of fracture healing in the human
tibia under realistic muscle loading and with an external fixator applied could predict
healing similar to that found in vivo [83]. The simulation was accomplished using a
discrete lattice modeling approach combined with a mechano-regulation algorithm
to describe the cellular processes involved in the healing process—namely prolifer-
ation, migration, apoptosis, and differentiation of cells. The main phases of fracture
healing were predicted by the simulation, including the bone resorption phase. Bone
healing was simulated beyond the reparative phase by modeling the transition of
woven bone into lamellar bone.
In another study, a mechano-regulatory bone healing model was attempted that
combined directly cellular mechanisms to mechanical stimulation during bone
healing. This was based on the belief that the cells serve as transducers during tissue
regeneration. The evolutions of MSCs, fibroblasts, chondrocytes, and osteoblasts as
well as the production of extracellular matrices of fibrous tissue, bone, and carti-
lage were calculated. Furthermore, the cells in the model within the matrix prolif-
erate, differentiate, migrate, and produced extracellular matrix, all at cell-phenotype
specific rate, according to the mechanical stimulation they experience. The poten-
tial of their model was evaluated using a 2-D FE model of a long bone osteotomy
[84]. The authors claimed that their model was able to accurately predict several
aspects of bone healing, including cell and tissue distributions during normal fracture
healing. Furthermore, it was able to predict experimentally established alterations
due to excessive mechanical stimulation, periosteal stripping, and impaired effects
of cartilage remodeling.
Experimental investigations have demonstrated that one of the primary mecha-
nisms for the course of bone healing is interfragmentary movement even though
there are also other variables that will have an influence on fracture healing [85]. The
effectiveness of computational models to address the complex relations between
tissue formation and mechanical environment was first proposed by García-Aznar
et al. [86] and later by Comiskey et al. [87] where they examined the formation of
callus in two cases of bone fracture healing. Compressive strain field experienced
by the immature callus tissues due to the interfragmentary movement was calculated
using plane strain models of the oblique fractures. The external formation of calluses
was determined using an optimization algorithm that iteratively excludes tissue that
encounters low strains from a large domain. A combined failure-repair mechanistic
computation model was also suggested to describe the healing process of a bone
fracture. The bone fracture gap was created in the model using interface elements to
connect the two fracture ends and to simulate the discontinuity in the displacement
field between fragments [85].
As mentioned above, predicting the key phases of fracture healing utilizing math-
ematical models and in particular FE simulations have been reported in a number
of studies [82–84, 88, 89]. The study by Grivas et al. attempted to address the limi-
tations of FE simulation in the prediction of cell proliferation during bone healing
[88]. The authors suggested that the application of a meshless approach where no
background cells were required for the numerical solution of the integrals would
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52 5 Understanding Bone Structures

address the shortfall in which the solution to diffusion equations in most studies is
achieved using the FE approach that nonetheless requires global remeshing in situ-
ations with moving or newly created surfaces or material phases. In their study, a
meshless local boundary integral equation method was used to derive predictions of
cell proliferation during bone healing in a 2-D fractured model.
It must be remembered that these structural properties of a fracture callus depend
collectively on the individual tissues, including cartilage, calcified cartilage, and
woven bone, and the spatial distribution of these tissues, as well as the overall
geometry of the callus.
Despite the aforementioned studies are focused on simulating numerically the
fracture healing process in long bones such as the femur, the same concept can be
employed in an oral environment. Above all, investigations have been carried out
to assess the possibility of bone remodeling and formation in addition to the risk of
further bone fracture induced by fixation plates used to treat mandibular fractures [90–
97]. It has been well-proven that the absence of excessive mobility or immobilization
is crucial for the unification of the fracture segments. Furthermore, this stability plays
a key role in the healing of both hard and soft tissues in the fractured or injured area.
This indicates that the fracture site must be stabilized to aid in the physiological
process toward normal bony healing using mechanical means. The application of
plate fixation should produce undisturbed primary fracture healing, and it has been
stated that the required fracture mobility essential to favor primary bone healing
should be no greater than 0.15 mm between the fracture surfaces [78, 95, 98–100].
Similarly, it has been hypothesized that the differentiation of callus tissue is
governed by the amount of biomechanical strain along existing calcified surfaces
in the fracture callus [101]. The study by Claes and Heigele predicted intramembra-
nous bone formation would occur for strains smaller than 5%, while endochondral
ossification for strains less than 15%. They also suggested that all other conditions
would result in fibrous cartilage or connective tissue [101]. Based on the observations
of their fracture experiments using metallic fixation devices, Orassi et al. postulated
that bone healing would take place at lower mechanical strains for fractures located
around the mandibular body and symphysis, and at higher strains for fractures around
the mandibular angle and condyles where the muscle forces are applied [90]. Their
findings were consistent with the observations made by Kimsal et al. in which they
assess the ideal fixation candidate as a less invasive fixation approach to fractures of
the mandibular angle using principal strains in the callus at the fracture site [97].

5.3 Bone Remodeling Around Dental Implants

The interface between the implant and bone tissue during mandibular movement is of
great concern to the osseointegration process as the mechanical environment of the
mandible may be altered by dental implants. This may also result in the remodeling
and adaptation of the surrounding cortical and cancellous bone tissues. As a result,
it is imperative that the effect of bone remodeling and its influence on the longevity
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5.3 Bone Remodeling Around Dental Implants 53

of implants and prostheses be considered in order to improve its performance and


reliability [57, 102].
During functional movements such as chewing, forces on the prosthesis will be
transferred to the supporting implants and this will lead to stresses being generated
within the bone tissue surrounding the implant. During the first year of function,
bone remodeling occurs in response to occlusal forces as well as establishing the
normal dimensions of the peri-implant soft tissues. Bone remodeling is categorized
as either constructive or destructive, and the changes in the internal stress state will
determine the type of remodeling that will take place in the bone tissue surrounding
the implant.
Bone resorption and stress shielding will occur if no load is transmitted from the
implant to the supporting bone tissues. On the other hand, abnormally high stress
concentration can result in implant failure. For these reasons, it is crucial to consider
the effect of bone remodeling on the performance of dental implants and prostheses
in order to improve its efficiency.
The mechanostat hypothesis for bones proposed by Frost focuses on how it adapts
their strength to the mechanical loads on them as well as how strain magnitudes might
affect the biological machinery of load-bearing bones [103, 104]. The hypothesis
further describes four microstrain zones and the role they play in mechanical adapta-
tion of bone tissue. If bone strain is less than a certain threshold, such as between 50
and 100 microstrain (equivalent to around 1 to 2 MPa), then disuse-mode remodeling
occurs and bone strength is reduced. Bone strain between 50 and 1500 microstrain
represents no net gain or loss in bone strength, and bone in this strain environment
remains in a steady state (lazy zone), and according to Frost, 1000 to 1500 micros-
train is equivalent to around 20 MPa. On the other hand, bone strain greater than 3000
microstrain (equivalent to around 60 MPa) could lead to physiological overload and
bone resorption will take place. Strains between 1500 and 3000 microstrain can be
considered to be mildly overloaded and repeated bone strain result in microscopic
fatigue damage in bone. Typically, this microdamage can be detected and repaired by
bone if the strain is below 3000 microstrains and this new or repaired bone is usually
in the form of woven bone [103, 104], which is weaker than lamellar bone [105]. It
has been suggested that this state of bone could be similar to an overloaded endosteal
implant attempting to alter the strain environment at the bone-implant interface back
to the steady-state zone [106]. Bone fractures in young adults occur if the strain
exceeds 25,000 microstrain or 120 MPa. An important note also is the stress values
mainly apply to cortical lamellar bone in healthy young adult mammals [103, 104].
It has been hypothesized that the mechanostat theory could also be applied to the
field of dental implantology and in particular, implants placed in the alveolar jaw,
but there were also concerns on the applicability of the strain thresholds identified
by Frost to the alveolar bone [107].
Achieving osseointegration will involve a number of factors such as the design,
geometry, and material composition of the implant, sufficient bone quality at the
implantation site, interaction at the bone-implant interface, surgical technique, and
the absence of overheating during preparation at the site of implantation.
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54 5 Understanding Bone Structures

Fig. 5.5 Simple illustration displaying the steps involved in bone remodeling calculation using the
FE approach. Modified from Isaksson [89]

The process of bone remodeling around dental implants has been simulated in a
number of studies using a variety of models (Fig. 5.5). Mathematical algorithms such
as mechano-regulation mechanisms and strain energy density algorithms have been
integrated into numerical models to study bone formation and osseointegration of
dental implants. In addition, time-dependent technique for imitating bone modeling
and remodeling in response to the daily loading history has also been adapted to
demonstrate bone remodeling induced by dental implants and fixed partial dentures.

5.3.1 Strain Energy Density

The 1970s saw the beginning of the development of the first mathematical theory
for bone remodeling with the theory of adaptive elasticity [108, 109]. A study was
conducted afterward utilizing a similar theory on the correlation between orthopedic
implants and long-term adaptive bone remodeling in both 2-D and 3-D FE models
[109]. The shape or bone density adaptations to different functional requirements
were governed by the strain energy density as a feedback control variable.
Strain energy density in their study was expressed in the general form of:

Strain energy density = 1 2εi j : σi j (5.1)
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5.3 Bone Remodeling Around Dental Implants 55

where σij and εij are the components of the local stress and strain tensors and the
strain energy density discusses the rate of variation in bone density (ρ) using the
following relation when it is applied to bone remodeling:

∂ρ
= C(S E Da − S E Dh ) (5.2)
∂t
where C is the rate of adaptation.
The homeostatic strain energy density (SEDh ) is referred to as the local actual
strain energy density, and the difference between the actual strain energy density
(SEDa ) and a site-specific homeostatic strain energy density was suggested to be the
driving force for adaptive activity. As previously suggested by Carter, bone is added
above and removed below certain thresholds of tissue loading [110]. A “lazy zone”
or a “dead zone” exists within these thresholds in which no net change in bone mass
occurs [108, 109, 111].
Adaptive activity is initiated if:

S E Da > (1 + s)S E Dh (5.3)

Or

S E Da < (1 − s)S E Dh (5.4)

where s is the threshold level, and the rate of variation in bone density in the “lazy
zone” can be described as:

∂ρ ⎨ C[S E Da − S E Dh (1 + s)]
= 0 (5.5)
∂t ⎩
C[S E Da − S E Dh (1 − s)]

If

S E Da > S E Dh (1 + s)
(1 − s)S E Dh ≤ S E Da ≤ (1 + s)S E Dh
S E Da < S E Dh (1 − s)

Recently, a FE analysis was carried out to determine the strain energy density in a
2-D mandibular model under normal chewing and biting forces. A load consisting of a
vertical component of 100 N and a lateral component of 10 N was applied to the three
teeth contained in the model (canine, lateral incisor, and central incisor). Included in
the 2-D model were enamel, dentin, pulp, cementum, periodontal ligament, gingiva,
cortical and trabecular bone. The effects of model parameters (boundary conditions,
adjacent teeth, initial bone density, reference value for the mechanical stimulus,
and width of the equilibrium zone) on the resulting trabecular bone density were
investigated [112].
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56 5 Understanding Bone Structures

The same strain energy density algorithm was applied in a number of studies where
bone remodeling was induced by the use of dental implants and was chosen as the
mechanical stimulus initially by Mellah et al. in 2004 to examine the stresses at the
bone-implant interface before and after osseointegration [113]. In another study, Li
and co-workers suggested an alternative mathematical model that describes changes
in bone density as a function of the mechanical stimulus [114]. Their proposed algo-
rithm includes an additional quadratic term based on the work carried out by Weinans
and co-workers [115] and can simulate both overload and underload resorptions that
frequently occur in dental implant treatments using the strain energy density as the
stimulus for bone remodeling. Their FE results demonstrated that bone resorption
occurred at the neck of the implant as a result of occlusal overload but then resorption
ceased after some time prior to reaching the coarse threads. The authors also noticed
from their simulation that the density of the bone deeper into the mandible increased
slightly due to the additional mechanical stimuli provided by the occlusal load, a
phenomenon observable in some clinical situation. This was similar to a number
of studies aimed at gaining an insight into the effects of mandibular bone remod-
eling induced by dental implantation particularly changes in bone density [116] and
stiffness over a period of 48 months [117]. The result of Lin et al., which were
qualitatively validated by comparing with the X-ray images from clinical follow-up,
displayed signs of visible bone apposition in the peri-implant cancellous region. The
study by Nuţu attempted to correlate the effect of initial bone quality and density
distribution as an essential factor for long-term survival of dental implants [118]. Two
strain energy density-based bone remodeling theories were applied (one of which
accounted for overload resorption).
It was also applied in a number of hypothetical and comparative studies. In 2010,
a modified remodeling algorithm based on existing theories including strain energy
density was used to examine the influence of various degrees of bone-implant contact
(between 25 and 100%) on bone remodeling following dental implantation through
a 2-D FE model [119]. Later, the effect of cusp inclination and occlusal loading on
mandibular bone remodeling was simulated [120]. Strain energy density obtained
from 2-D plane strain FEA was used as the mechanical stimulus to drive cortical and
cancellous bone remodeling in a bucco-lingual mandibular section. It was applied
to study the relationship between stress shielding and low-stiffness implants [121].
Marginal bone loss around low-stiffness implants was determined by applying the
calculated strain energy density values to the “lazy zone” range as suggested by
Huiskes et al. [109]. Recently, the influence of subcrestal implant placement depths
(between 0 and 3 mm) on cortical and cancellous bone remodeling over the first
12 months after final prosthesis delivery was investigated [122].
The morphology of bone around dental implants with the consideration of both
short-term and long-term bone healing was also predicted using a hybrid two-step
algorithm in which the short-term stage was simulated using a tissue differentiation
model [123]. The distribution of strain, fluid velocity, and stem cell diffusion in the
short-term or initial model was first calculated by FEM. Granulation tissues were
then differentiated into various tissue phenotypes based on the mechano-regulation
algorithm. The authors also claimed that their hybrid model was able of reproducing a
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5.3 Bone Remodeling Around Dental Implants 57

number of features discovered in experiments such as high-strength bone connective


tissue bands, stress shielding effect, and marginal bone loss.
The remodeling of both maxillary and mandibular bone also plays a vital role in
the long-term application and survival of implant-supported fixed partial dentures
and overdentures. Using an adaptive algorithm that included an overloading bone
resorption process, bone remodeling simulations were carried out on two-unit fixed
partial dentures with and without cantilever configuration incorporated into a patient-
specific 3-D FE model of a maxillary bone with two absent central incisors [124].
Rungsiyakull et al. explored the biomechanics and associated bone remodeling
responses between implant-implant-supported and tooth-implant-supported fixed
partial dentures. The strain energy density induced by occlusal loading was used as a
mechanical stimulus for driving the bone remodeling [125]. Later, the stress distribu-
tion in the mandible and changes in bone density was attempted by Li and co-workers
to examine the effect of implant number on the remodeling of the peri-implant bone
and posterior mandible under occlusal force induced by implant-supported over-
dentures [126]. It has also been suggested that the combination of FEA containing
mechanobiological stimuli such as strain energy density and medical imaging such
as positron emission tomography (PET) could offer a new approach to clinically
monitor and examine bone remodeling driven by fixed partial dentures [127].

5.3.2 Mechanobiological Approach

As discussed previously, the regeneration of skeletal tissue is achieved through a


cascade of biological process that may involve differentiation of pluripotential tissue,
endochondral ossification, and bone remodeling. The local tissue mechanical loading
history has been shown to influence all these processes in a significant manner
[128]. Mechanobiology is the study on how mechanical loads regulate biological
processes and responses of cells within tissue [129–131]. Gaining deeper insight
into the mechanobiological behavior of bone tissue is made possible through the
combined use of FEM and mathematical models.
Determining the quantitative rules that govern the effects of mechanical loading on
tissue differentiation, growth, adaption, and maintenance has been attempted using
computational mechanobiology [89, 132]. According to Isaksson, the modeling is
based on the principle that local mechanical variables stimulate cell expression to
regulate tissue density, structure, or composition. Moreover, modeling considera-
tions include force application at the boundary, transmission of force through the
tissue matrix, mechanosensation and transduction by cells, and transformation of
extracellular matrix characteristics [89].
Physical forces play a key role in the differentiation of the cell populations which
arise over the healing period during bone regeneration, and a number of hypothesis for
the mechano-regulation of tissue differentiation have been developed by comparing
differentiation patterns during tissue repair to predict the mechanical environment
within the mesenchymal tissue [131, 133]. Experimental evidence by Caplan has
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58 5 Understanding Bone Structures

demonstrated the capacity of MSCs to differentiate into bone and cartilage as well
as other musculoskeletal tissues [134, 135].
The theory concerning the role of mechanical stimuli and the regulation of tissue
differentiation within a fracture callus was first suggested in a fracture callus study
by Pauwels, and it was based on the understanding that stress and deformation of the
MSCs are the result of physical factors and that the cell differentiation pathway could
be governed by these stimuli [89, 131, 136]. The work of Pauwels hypothesized the
formation of fibrous and bone tissues was the consequence of MSCs being stimu-
lated into fibroblasts due to shear strain. Similarly, cartilaginous tissue is created as
a result of hydrostatic compression stimulating MSCs into chondrocytes. Further-
more, Pauwel also hypothesized that a stable mechanical environment is needed for
primary bone formation and the necessity for soft tissues to generate this low strain
environment in order for endochondral bone formation to proceed [89, 131, 136].
The histological pattern of fracture healing has been theorized to be regulated at
least to a certain degree by the local mechanical strains in the interfragmentary region.
The term “interfragmentary strain” was used to describe the strain generated in the
fracture gap when the fracture fragments dislocate relative to each other as soon as
a load is applied to the fracture bone [100, 137–140]. The interfragmentary strain is
calculated by dividing the magnitude of the gap movement in the longitudinal or axial
direction by the size of the gap. The notion behind the interfragmentary strain theory
is that tissues located within the fracture gap must be able to sustain the interfragmen-
tary strain without experiencing rupture. Tissue differentiation within the fracture gap
is governed by the scale of the interfragmentary strain. Bone tissue has the lowest
tolerance level to this strain, while on the other hand granulation tissue has the highest
tolerance. Cartilage has an intermediate tolerance level. As stated by the interfrag-
mentary strain theory, granulation tissue is the only tissue that can be formed if the
intrafragmentary strain is high. Once this tissue is formed, interfragmentary strain
will be reduced as the tissues in the fracture gap stiffens (formation of callus). An
environment more ideal for chondrogenesis and where chondrocytes can maintain the
intrafragmentary strain and proliferate is created by this reduction in the movement
of the fracture fragments [100, 131, 137–140]. A number of studies have reported
the use of FE modeling to predict changes in mechanical properties during fracture
healing. The study by Cheal et al. [138] predicted the complex tissue strains using a
non-linear 3-D FE model of the interfragmentary tissue at the initial stage of healing.
Later, Gardner and co-workers [141] developed 2-D FE models of a diaphyseal tibial
fracture. Stress and strain distributions in the callus and bone were calculated from
peak interfragmentary displacements measured during natural walking activity and
were correlated with the subsequently observed pattern of tissue differentiation and
maturation of the callus. Their study also confirmed the growth and stiffening of
the external callus progressively reduced the interfragmentary gap strain. Lacroix
et al. [142] created an algorithm to predict the time course of intramembranous and
endochondral ossification and this algorithm assumes that there are precursor cells
in the undifferentiated tissue and that these cells differentiate into either fibroblasts,
chondrocytes, or osteoblasts, based on a combination of biophysical stimuli derived
from strain in the collagenous matrix and flow of the interstitial fluid. It was tested
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5.3 Bone Remodeling Around Dental Implants 59

in an investigation of the fracture healing of a long bone using an axisymmetric FE


model. They suggested that the origin of the precursor cells will have a fundamental
effect on the healing pattern and on the rate of reduction of the interfragmentary
strain.
FEA was also used by Cleas and co-workers to support the theory that correlates
the local tissue formation in a fracture gap to the local stress and strain and that
the magnitudes of hydrostatic pressure and strain along existing calcified surfaces in
the fracture callus govern the differentiation of the callus tissue, which was initially
suggested by Carter and co-workers in 1987 [128, 143, 144]. The theory takes into
consideration the intermittent or repeated mechanical forces which represent the
loading history on the chondro-osseous skeleton and the local tissue stress history
plays a vital part in determining the biology of connective tissue [144]. The results of
their 2-D FE analysis suggested that intermittent hydrostatic (dilatational) stresses
could play a significant role in affecting revascularization and tissue differentia-
tion as well as regulating the morphological patterns of initial fracture healing [143].
Furthermore, according to Carter et al., cyclic motion and the associated shear stresses
cause cell proliferation and the production of a large callus during the early stages of
fracture healing. Fibrocartilage development is predicted to take place under tensile
strain with a superimposed hydrostatic compressive stress. The production of fibrous
tissue occurs when tissue experienced high tensile strain. Direct intramembranous
bone formation is allowed in areas of low stress and strain. Intramembranous ossifica-
tion could be encouraged by low to moderate degrees of tensile strain and hydrostatic
tensile stress. Hydrostatic compressive stress could spur chondrogenesis, and it can
be promoted by poor vascularity in an otherwise osteogenic environment [128]. Claes
and co-workers hypothesized that the scales of hydrostatic pressure and strain along
existing calcified surfaces in the fracture callus will control the differentiation of the
callus tissue. In their study, the local stresses and strains in the callus as determined
from a FE model were compared to the histological observations using an animal
fracture model, and this permits the attribution of certain mechanical scenarios to the
kind of tissue differentiation. The formation of intramembranous bone will occur for
hydrostatic pressures smaller than 0.15 MPa and strains smaller than approximately
5%. If the hydrostatic pressure was more than 0.15 MPa and strains smaller than
15%, this situation would stimulate endochondral ossification. Moreover, all other
conditions appeared to result in fibrous cartilage or connective tissue [77, 101].
In addition to mechanical strain, microdamage as the stimulus driving cellular
responses to predict bone remodeling has also been examined, and certain aspects
of bone remodeling have been successfully predicted using damage-based models
[145]. The study by McNamara and Prendergast [145] examined the theory that bone
remodeling could be governed by signals due to both microdamage and strain. This
was based on experimental data implicating both stimuli in bone cell regulation.
Four mechano-regulation algorithms were examined (strain, damage, combination
of strain and damage, and either strain or damage) with damage-adaptive remod-
eling prioritized when damage is above a critical level. Each algorithm is applied
with both osteocyte cell sensors (internal) and bone lining cell sensors (surface) and
used to predict a bone multicellular unit (BMU) remodeling on the surface of a
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60 5 Understanding Bone Structures

bone trabecula. Utilizing this approach, the effect of implant geometry (length and
diameter) on its long-term stability was examined [146]. The temporal evolution of
porosity and microstructural damage of the peri-implant bone were the variables
investigated in their study.
FE simulations were carried out in the study by Wang et al. [147] using a model that
combined both adaptive bone remodeling and microdamage-based mechano-sensory
mechanisms to predict the evolution of the trabecular architecture around dental
implants. Their study was based on the value of damage accumulation (ω) determined
using Miner’s rule as suggested in the study by McNamara and Prendergast [145]:

1
ω̇ = (5.6)
Nf

where Nf is defined as the number of cycles to failure of the material at a given stress
level.
An empirical equation can be utilized to determine the value of Nf for bone
according to a study by Carter et al. [148]:

log N f = H log σ i + J · T + K · ρ i + M (5.7)

where σ is the stress in MPa, T is the temperature (°C), ρ is the density of the material
in g/cm3 . H, J, K, and M are empirical constants.
The damage accumulates can then be calculated using the following equation:

t
ω = ∫ ω̇dt (5.8)
0

where ω is the state of local damage bone tissue, and t is the duration of the calculation.
Once the damage accumulation (ω) is below the critical damage threshold, strain-
adaptive remodeling was considered to be the determining mechanism in the remod-
eling process. If the damage accumulation value exceeds the damage threshold on
the other hand, then damage-induced remodeling will take over. The combined algo-
rithms of adaptive and microdamage remodeling will alter the local bone density
values. Using the equation derived by Currey [8], the value of Young’s modulus is
updated based on the change in the bone density value:

E i = Cρin (5.9)

According to the authors, the suggested algorithms were shown to be effective


in simulating the remodeling process of trabecular architecture around the dental
implant systems and the predicted orientational and ladder-like architecture around
the implants were similar to those observed in animal experiments and clinical
studies.
The theory behind poroelasticity centers on the interaction of deformation and
fluid flow in a fluid-saturated porous medium, and it has been applied to the study
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5.3 Bone Remodeling Around Dental Implants 61

of bone tissue for many decades [149]. It is evident that the tissue itself is a material
composed of both fluid and solid constituents and since the cells that undergo differ-
entiation are contained in the fluid until such time as they become precursors for
tissue-forming cells, Prendergast and Huiskes hypothesized that a model describing
the tissue behavior derived from the fundamental biphasic nature of tissue would
be more accurate than a model based on the elastic approach despite the conve-
nience [150]. Based on the observations from their study in which an axisymmetric
2-D FE model of the gap tissue and surrounding cancellous bone was developed to
investigate the biomechanical behavior of the environment surrounding the implant,
the prediction of osteogenic index was more suitable when the tissue was modeled
as a biphasic material. The study by Prendergast et al. [151] further highlighted the
necessity for biphasic analysis in which bone tissue is modeled as a biphasic material
composed of both solid and fluid constituents. Using a biphasic FE model, the inter-
facial tissue formation adjacent to a micromotion device implanted into the condyles
of dogs was investigated. Their results showed as tissue differentiation progressed,
subtle but systematic mechanical changes took place on cells in the interfacial tissue.
In particular, the implant changed to being governed by the maximum-available load
(force-control) rather than being regulated by the maximum-allowable displacement
(motion-control) as the forces opposing motion increase. This resulted in a reduc-
tion in the velocity of the fluid phase relative to the solid phase and a decrease in
interstitial fluid pressure accompanied by a reduction in peri-prosthetic tissue strains
[151]. This approach was later used in another study to examine bone regeneration
within the callus of an osteotomized mandible. The stimulus regulating tissue differ-
entiation within the callus was hypothesized to be a function of the strain and fluid
flow computed by the poroelastic FE model. This model was then used to investigate
tissue differentiation during a 15-day latency period, defined as the time between the
day of the osteotomy and the day when the first distraction is given to the device
[152].
Later, a mechano-regulatory tissue differentiation model that takes into consider-
ation the stimuli through the solid and the fluid components of the healing tissue as
well as the diffusion of pluripotent stem cells into the healing callus was used in a
study to examine the effect of immediate loading on the peri-implant bone healing.
The influence of micromotion, size of the healing callus, and thread design on the
length of the bone-to-implant contact and bone volume formed in the healing callus
were examined [153]. Their work was further expanded in a later study in which
the long-term osseointegration and bone remodeling around dental implants were
examined by simulating bone healing followed by bone remodeling process. The
assumption that wound healing and remodeling around oral implants would be the
same as in long bone. Development of soft tissue was observed both in the coronal
region due to high fluid velocity, and on the vertical sides of the healing gap due
to high shear stress. Furthermore, tissue between the implant threads differentiated
into bone during the healing phase with small implant micromotion but resorbed
during remodeling. Conversely, higher percentage of the healing region differenti-
ated into soft tissue with large implant micromotion resulting in smaller volume of
bone tissue available for remodeling. However, the remaining bone region developed
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62 5 Understanding Bone Structures

higher-density bone tissue [154]. The work Chou and Müftü [153] was later used
by Li et al. [155] to validate their results when the authors attempted to examine the
influence of implant geometry on biophysical stimuli and healing patterns.
The mechanobiological approach was also used by Vanegas-Acosta et al. [156] in
an attempt to describe the process of osseointegration at the bone-implant interface in
relations to the implant surface and mechanical and biological factors. In their study,
an injury area of 1 μm measured from the implant surface was defined for equations
related to the concentration of osteogenesis and osteogenic chemical compound
which resembles the contact area between the tissues in formation and the implant
surface. Their study also assumed that new osteoid formation in the injury area is
dependent on the displacement of fibrin matrix, and subsequently, the mechanical
properties of tissue are influenced by surface roughness.

5.3.3 Stanford Theory

Developed originally by Carter [144] and further extended by Beauprè et al. [157], the
so-called Stanford Theory is a time-dependent technique for imitating bone modeling
and remodeling in response to the daily loading history.
In their approach, the daily tissue level stress stimulus (ψb ) was defined by the
following equation, where ni is the number of cycles of load type i, and m is the
stress component:
  m1

ψb = n i σim (5.10)
d

The continuum level effective stress (σi ) can be defined as:



σi = 2EU (5.11)

where U is the continuum strain energy density and E is the continuum average
Young’s modulus. In addition, the authors devised an equation that can be applied
to both internal and external remodeling, and this can be applied directly to estimate
the rate of bone apposition or resorption on external surfaces.
The bone apposition or resorption rate (ṙ) can be expressed as:

 ⎨ (ψb − ψb·as )c + c · w
ṙ μm day = 0 (5.12)

(ψb − ψb·as )c − c · w
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5.4 Concluding Remarks 63

If

[(ψb − ψb·as ) < −w]


[−w ≤ (ψb − ψb·as )] ≤ w
[(ψb − ψb·as ) > w]

where c is the empirical rate constant, w is half the width of the central, normal activity
region, and ψb.as is the average daily tissue level attractor state stress stimulus.
This algorithm was first adopted by Eser et al. to predict time-dependent biome-
chanics and remodeling of bone around immediately loaded dental implants with
various macrogeometric designs and later in patients with reduced bone width using
a 3-D FE model [158, 159]. Sotto-Maior et al. [160] simulated bone remodeling
around single implants of different lengths (7, 10, and 13 mm) and to validate the
theoretical prediction with the clinical findings of crestal bone loss. Occlusal loading
cycles of 200 N were applied to the implants to simulate daily mastication, and bone
remodeling was examined via changes in the strain energy density of bone after 3,
6, and 12 months of function.

5.4 Concluding Remarks

The finite element method can be used to calculate local stress–strain distributions
in geometrically complex structures. The predictive accuracy of the finite element
model is influenced by the geometric detail of the object to be modeled, the material
properties, and the applied boundary conditions. Finite element analysis has become
widely used in all biomechanical fields, especially for assessing stresses and strains
in dental implants and the surrounding bone structures as well as in normal bone.
Bone remodeling around various options for tooth restoration can be examined under
functional movements and any possible problems such as stress shielding eliminated
by proper implant design and surgical protocol prior to implantation. Furthermore,
the use of numerical models to simulate the process of fracture healing may prove to
be advantageous when deciding the optimal mechanical-based treatment for fracture
fixation after a trauma. Nevertheless, considerations need to be taken to account for
the variations between FEA simulation and the natural healing process of the human
body. For example, in addition to being governed by mechanical factors, bone healing
is also regulated by chemical, genetic, and biological factors. These factors need to
be addressed in order to improve the predictive accuracy of the bone fracture healing
process.
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64 5 Understanding Bone Structures

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96. Vajgel A, Camargo IB, Willmersdorf RB et al (2013) Comparative finite element analysis
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Chapter 6
Patient-Specific Modeling

The usefulness of finite element analysis (FEA) from a clinical point of view as a
biomechanical foundation in the construction of a predictive tool is ideal for deter-
mining the influence of a specific implant design on the magnitude of bone remod-
eling and osseointegration and avoiding any potential issues such as stress shielding
and bone resorption based on the anatomical conditions of individual patients such
as bone health and muscle force.
The application of computerized modeling technique will have countless applica-
tions in both craniomaxillofacial surgery and dentistry, not only at a research level but
also at a clinical level. For instance, it is a common practice to generate a computer
model based on data from CT scans and micro-CT or other suitable imaging tech-
niques such as magnetic resonance imaging (MRI) of individual patients [1]. 2-D
or 3-D finite element (FE) meshes are created by importing the image data into
specialized modeling software where this information is converted into solid models
(Fig. 6.1).
This model can then be utilized in the following applications:
• Traumatology: Trauma and dental surgeons can determine through accurate
patient-specific 3-D modeling the best form and engineering requirements of
hardware such as bone fixation devices used in the treatment of injuries such as
mandibular fractures. This approach enables both a reduction and fixation of frac-
tures while minimizing the number and size of the osteosynthesis plates used at the
same time. Above all, bone remodeling and the healing process of bone fractures
have been simulated using the combination of FEA and patient-specific modeling.
Computational models and simulations of fracture healing process may prove to
be useful in defining the optimal mechanical-based treatments after a trauma or
accident.
• Temporomandibular joint surgery: Intense scrutiny has been placed on
temporomandibular joint prostheses in the past as a consequence of breakdowns
primarily due to material failure. It is anticipated that patient requiring temporo-
mandibular joint replacement can benefit from improvements in the design and

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 71
A. H. Choi, Bone Remodeling and Osseointegration of Implants, Tissue Repair
and Reconstruction, https://doi.org/10.1007/978-981-99-1425-8_6
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72 6 Patient-Specific Modeling

Fig. 6.1 Illustration


showing the stages involved
in the creation of a
patient-specific FE model

material used in these prostheses based on computational simulation. Further-


more, computational modeling technology can also play a part in the in vitro
examination of these prostheses by fine-tuning its design so that damage due to
numerous materials failures in the past can be avoided.
• Distraction osteogenesis: The success of distraction osteogenesis of the mandible
depends on the accurate planning of the distraction vector required to produce
the final position of the distracted segment. Currently, this planning process can
be refined through the combined use of FEA and patient-specific computational
modeling, and in particular, the beginning of the widespread utilization of intraoral
multidirectional distraction devices.
• Dental implants: Determining the correct implant placement location as well
as the number, size, and configuration of implants needed is now possible in an
effort to address the patient’s restorative and functional needs. In such instance, the
dental clinician or dentist is able to estimate the functional loads that an implant-
supported restoration may develop based on the patient’s own bone properties and
muscle forces. Accordingly, any essential surgeries can be planned beforehand
by the clinician in an effort to avoid harmful overloading on the restoration that
could jeopardize the success of the treatment plan. In doing so, the likelihood
of over-treatment can also be prevented. Moreover, it is possible to simulate and
predict bone remodeling and osseointegration induced by dental implants using
mathematical algorithms.
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6.1 Mechanical Properties of Bone Tissue from CT Scans 73

• Restorative dentistry: In a similar fashion to dental implant restorations, different


restorative tooth options can be investigated under simulated functional loading
and designed to resist these loads prior to manufacturing.
• Pathology resection and reconstruction: Reconstructions after the resection
of various pathologies involving the mandible can be conducted using patient-
specific models so that form and function are returned to the premorbid state as
closely as possible.
• Aesthetic facial surgery: Patient-specific computational modeling can also be
utilized to investigate various aspects of facial bone osteotomies such as post-
operative functional change and stability of the orthognathic movements.

6.1 Mechanical Properties of Bone Tissue from CT Scans

As discussed earlier, assigning appropriate physical and mechanical properties of


bone tissues to a FEA model is of paramount importance, as it will strongly influ-
ence the distributions of stresses, strains, and deformations within a structure. A
suitable approximation of the physical and mechanical properties of bone tissue can
be acquired using CT scans. Subsequently, a more relevant physiological model on
a subject-specific basis can be achieved using this approach.

6.1.1 Hounsfield Units to Density

The raw CT values can be converted into Hounsfield units (HU) according to the
study by Rho et al. [2] by relating the bone values to air where the value of HU is −
1000 [3] and to water where the value of HU is zero using the following equation:

C T − C TH2 O
HU = 1000 (6.1)
C TH2 O − C Tair

In recent years, the introduction of cone-beam CT (CBCT) has permitted dental


clinicians to examine craniofacial structures in 3-D at a relatively high spatial reso-
lution with less exposure time and radiation dose than the conventional clinical
multidetector CT [4, 5]. Consequently, this resulted in the widespread application of
CBCT in dentistry for 3-D imaging and in the diagnostics of dental complications
[5, 6]. It has also been suggested that the 3-D image generated by CBCT allows for
detailed morphological examination of bone [5]. According to the review by Pauwels
et al. [4], it is unclear if the gray values derived from CBCT units are similar to the
HU values obtained from CT scanners. In 2010, Mah et al. investigated the relation-
ship between gray levels in dental CBCT and HU in CBCT scanners [7]. The authors
demonstrated that a linear relationship between the attenuation coefficients and the
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74 6 Patient-Specific Modeling

gray levels of each material tested. Furthermore, by utilizing linear attenuation coef-
ficients, HU can be calculated from the gray levels in dental CBCT scanners using a
standard equation:

μmaterial − μ H2 O
HU = 1000 (6.2)
μ H2 O

where μmaterial and μ H2 O are the linear attenuation coefficients for the material and
water, respectively.
Bone density is defined as mean value expressed in HU in each pixel. The apparent
density of bone (ρ app ) can be determined using a linear equation from HU according
to Rho et al. [2]:

ρapp = a + b · HU (6.3)

A linear calibration derived from two reference points in one of the CT scan slices
is used to determine the values of a and b [8]. Non-bone condition should represent
the first reference point where the density should be equal to 0 g/cm3 . The second
reference point can be cortical bone with an average density of 1.768 g/cm3 taken
from 17 mandibular samples [9] or between 1.85 and 2.0 g/cm3 obtained from both
edentulous and dentate human mandibular cortical bones according to the studies by
Dechow and co-workers [10, 11]. The CT gray values (HU) of both of the reference
points are then substituted into Eq. 6.3 together with the data on apparent density. The
apparent density can be determined at any point in bone using linear interpolation of
the raw CT gray values once the values of a and b are calculated.
According to the study by Keyak et al. [12], correlations between various measures
of density are needed in order to compare numerous Young’s modulus-density rela-
tions that have been published over the years. The relationships between different
density measurements such as ash density (ρash ), apparent dry density (ρdry ), quanti-
tative CT equivalent mineral density (ρQCT ), apparent wet density (ρapp ), as well as
the connection between density and bone tissue volume can be expressed mathemat-
ically using the equations shown in Table 6.1. Bone tissue ash mass, which is used to
determine the ash density (ρash ), can be obtained based on the methods described by
Galante et al. [13] and later by Keyak et al. [12], and the process essentially involves
weighing the tissue after defatting and firing in a furnace at an elevated temperature
over a period of time. Apparent dry density (ρdry ) can be determined by weighing
tissue samples in air once it has been defatted and dried at moderate temperatures
and dividing it by the total specimen volume. Mineral equivalent density (ρQCT )
can be converted to ash density (ρash ) using either dipotassium hydrogen phosphate
(K2 HPO4 ) phantoms [12] or hydroxyapatite phantoms [14] and the average HU value
of all voxels within a region of interest of the known calibration phantom sample
rods [15].
As discussed in the reviews by Helgason et al. [17] and later by Poelert et al. [18],
the biggest challenge is determining which Young’s modulus-density relationship is
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6.1 Mechanical Properties of Bone Tissue from CT Scans 75

Table 6.1 Mathematical conversions between the various measures of density using apparent
density (ρapp ) as input
Density (g/cm3 ) Conversion Reference
ρash 0.55 · ρapp Keyak et al. [12]
ρdry 0.92 · ρapp Keyak et al. [12]
ρapp
Bone volume/total volume (BV/TV) 1.8 Gibson [16]

ρQCT [hydroxyapatite phantoms] (0.55ρapp −0.0789) Schileo et al. [14]


0.877

ρQCT [K2 HPO4 phantoms] (0.55ρapp −0.0389) Keyak et al. [12]


1.06

the most appropriate. The vast majority of these Young’s modulus-density relation-
ships are expressed either as a linear form (Eq. 6.4) or as an exponential function
(Eq. 6.5):

E =a+b·ρ (6.4)

E = Cρ d (6.5)

where a, b, c, and d are constants derived by statistical techniques based on mechanical


testing results.
It should be mentioned that there are substantial differences between the proposed
relationships. The lack of standardized testing approach (such as how strain is
measured), sample preparation, and the angle between the main trabecular orientation
and loading direction may to a certain degree contribute to these variations observed
between different studies. The review by Helgason et al. [17] also commented on the
accuracy of utilizing a single Young’s modulus-density relationship over the entire
range of densities or multiple relationships are needed for cortical and cancellous
bone.
Extensive investigations have been carried out since the late 1970s to study
the mathematical correlations between Young’s modulus of human cortical and
cancellous bone and the apparent density values, and these numerical relation-
ships are considerably different from each other [17]. A greater number of Young’s
modulus-density relationships can be found in the review by Helgason et al. [17].

6.1.2 Cortical Bone

A power-law relationship was suggested by Carter and co-workers that could be


utilized to calculate Young’s modulus (E) of both cortical and cancellous bone based
on the apparent density values [19–21]:

E = Aρapp
B
(6.6)
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76 6 Patient-Specific Modeling

where A and B are constants derived experimentally. Equation 6.6 can be rearranged
to give:

log E = log A + B log ρapp (6.7)

Subsequently, a linear relationship exists between the apparent density and


Young’s modulus if log E is plotted against log ρapp on a graph. The gradient or
the slope of the line will be the value of B and log A is the intercept with the y-
axis. Carter and co-workers [19–21] concluded that axial Young’s modulus in GPa
is calculated using the apparent density to the third power and the strain rate š to the
power of 0.06. As a result, Eq. 6.6 can be rewritten as:

E = 3.79 · ε
0.06
· ρapp
3
(6.8)

where š is in inverse seconds and ρapp in g/cm3 . Carter and co-workers [19–21]
further concluded that the power-law relationship has been shown to be valid for
all bone tissues within the skeleton. This also enables meaningful predictions and
comparisons of strength and stiffness of bone based on in vivo density measurements.
It has been suggested that the stiffness of compact bone was non-linearly and
highly dependent on its apparent density, bone volume fraction, and porosity [22].
Young’s modulus increases both as a power of increasing apparent density and bone
tissue volume but decreases as a power of increasing porosity. Subsequently, the
power-law relation between Young’s modulus (in GPa) and apparent density (in
g/cm3 ) was proposed:

E = 0.09ρapp
7.4
(6.9)

Destructive mechanical testing on 496 cubic specimens of human cortical and


trabecular bones taken from the lumbar vertebrae and femoral metaphyses and diaph-
ysis was carried out in the study by Keller [23] along the superior-inferior axis. The
results showed the apparent dry density ranged from 0.05 to 1.89 g/cm3 and the
apparent ash density ranged between 0.03 and 1.22 g/cm3 . Based on these find-
ings, the following power-law relationship between Young’s modulus (in GPa) and
apparent ash density (in g/cm3 ) was proposed:

E = 10.5ρash
2.75±0.04
(6.10)

Similarly, Jacobs [24] also suggested the relationship between Young’s modulus
(in GPa) and apparent density (in g/cm3 ):
g
E = 2.014ρapp
2.5
(if ρapp ≤ 1.2 ) (6.11)
cm3
g
E = 1.763ρapp
3.2
(if ρapp > 1.2 ) (6.12)
cm3
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6.1 Mechanical Properties of Bone Tissue from CT Scans 77

Later, a linear relationship between apparent density (in g/cm3 ) and Young’s
modulus of cortical bone (in GPa) was hypothesized by Lotz et al. [25] when they
investigated the structural behavior of specimens harvested from the metaphyseal
shell of the cervical and intertrochanteric regions of human proximal femora. All
specimens were oriented in either the local longitudinal or transverse directions.

E = −13.43 + 14.261ρapp (6.13)

Snyder and Schneider [26] examined the possibility of estimating the mechanical
properties of cortical bone using a CT system typically employed in the clinical
setting. Samples from the mid-diaphyses of adult human tibiae were tested in three-
point bending to failure and the mechanical properties as well as the density and ash
fraction determined. Hence, the following equation was proposed:

E = 3.891ρapp
2.39
(6.14)

where E is in GPa and apparent density is in g/cm3 .


Similarly, Rho et al. [2] also developed bone-specific relationships to predict
Young’s modulus from density and CT numbers in human bone. Seventy-two cortical
bone specimens were obtained from the mandibles of eight fresh un-embalmed
human cadavers: three transverse sections at 40, 60, and 80% of the total bone length
and three annular samples originated from the buccal, lingual, and inferior aspects of
the mandibular corpus. According to their study, the increase in percentage in bone
length signifies the positions from the chin to the ramus. Three linear relationships
were derived between Young’s modulus (in GPa) and apparent density for the three
orthogonal directions:

E 1 = 6.382 + 0.255E 3 (6.15)

E 1 = −13.05 + 13ρ (6.16)

E 3 = −23.93 + 24ρ (6.17)

where 1 is the radial direction and 3 is the superior-inferior direction and apparent
density in g/cm3 .

6.1.3 Cancellous Bone

Rice et al. [27] presented a statistical analysis of the pooled data from several exper-
iments centered on the dependence of Young’s modulus of cancellous bone and
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78 6 Patient-Specific Modeling

apparent density. Their findings revealed that Young’s modulus is proportional to the
square of apparent density of the tissue.
In the longitudinal direction:

E compr ession = 0.06 + 0.90ρapp


2
(6.18)

E tension = 0.06 + 1.65ρapp


2
(6.19)

In the transverse direction:

E compr ession = 0.06 − 0.15ρapp


2
(6.20)

E tension = 0.06 + 0.60ρapp


2
(6.21)

A regression was suggested by Hodgskinson and Currey [28] that can be applied to
describe the relationship between the apparent density (in g/cm3 ) and mean Young’s
modulus (in MPa) of human cancellous bone:

E mean = 0.003715ρapp
1.96
(6.22)

O’Mahony et al. [29] also determined Young’s modulus values in three orthog-
onal directions for cancellous bone taken from an edentulous mandible, and the
relationship between apparent wet density and Young’s modulus (in MPa) was
determined.

E Mesio−distal = 2349ρwet
2.15
(6.23)

E Bucco−lingual = 1274ρwet
2.12
(6.24)

E I n f er o−superior = 194ρwet
1
(6.25)

The correlation between mineral density measured via QCT (g/cm3 ) and Young’s
modulus of human vertebral trabecular bone (in MPa) were predicted using both the
linear and power-law models [30]:

E = −34.7 + 3230ρ QC T (6.26)

E = 2980ρ QC
1.05
T (6.27)

In addition, linear and power-law relations were also derived based on the apparent
wet density and used as a comparison:
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6.2 Muscle Forces and other Boundary Conditions 79

E = −97.1 + 2130ρwet (6.28)

E = 2580ρwet
1.34
(6.29)

Later, Morgan and co-workers [31] proposed power-law regressions between


Young’s modulus (in MPa) and apparent density (in g/cm3 ) of human trabecular
bone samples from various anatomic sites:

E = 7540ρapp
1.72
(6.30)

The reported range:

E = 10550ρapp
1.94
(6.31)

The mean regression reported when the data from all anatomic sites were pooled:

E = 8920ρapp
1.83
(6.32)

6.2 Muscle Forces and other Boundary Conditions

It is vital to determine appropriate magnitudes of muscle forces to be applied to a


patient-specific mathematical model if the intention is to examine the in vivo biome-
chanical behavior of bone, particularly the mandible given the fact that muscular
forces cannot be measured directly under non-invasive conditions [32–35]. The
following steps are used to estimate the force magnitudes of masticatory muscles
during various functional movements of the mandible such as clenching, opening,
and protrusion [32–34]:
I. All the forces are assumed to have an equal magnitude on both sides of the
mandible and to be symmetrical with respect to the mid-line.
II. Vectors can be used to represent the forces exerted by contracting muscles.
The direction of these vectors can be defined by connecting lines between the
insertions of the muscles and the centroids of their origins.
III. The maximum force that a muscle can exert can be determined using the value
of maximum muscle tension, which relates directly to its physiological cross-
sectional area.
IV. The lines of masticatory muscle actions and their moment arms are calculated.
V. The moments produced by the reaction forces applied at the condylar region
must be equal to the moments produced by the sum of the bite and applied
muscle forces.
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80 6 Patient-Specific Modeling

Table 6.2 Muscle actions


Muscles of Mastication Actions
during mastication [34]
Digastrics (openers) Depression of the mandible
Masseter Elevation of the mandible
Temporalis Elevation of the mandible
Medial pterygoid Elevation and protrusion of the
mandible
Lateral pterygoid Protrusion of the mandible

Table 6.3 Magnitudes of


Force magnitude (N)
bite, muscle, and joint
reaction forces (N) acting on Masseter 340.0
the mandible during Temporalis (anterior + posterior) 528.6
simulated clenching (one side
Lateral pterygoid 378.0
only)
Medial pterygoid 191.4
Openers 155.9
Bite force 403.7
Joint reaction force 471.9

As previously mentioned, muscles provide the energy to move the mandible and
permit functioning of the masticatory system. Despite being previously ignored in
the biomechanical analysis of the muscles of mastication, the digastrics also play a
vital role in mandibular depression (Table 6.2). In the works of Choi et al. [34, 36,
37], all muscles were assumed to be active during clenching. The reaction forces
were assumed to be acting at the center of the condyles (Table 6.3).

6.3 Concluding Remarks

The creation of a patient-specific 3-D model using appropriate imaging technolo-


gies is already a common practice. The developed model can also be coupled with
computer-aided designs and computer-assisted manufacturing to produce dental
structures and restorations with greater accuracy and relative ease. Furthermore,
patient-specific implants, tissue engineering scaffolds, and fracture fixation devices
for bone tissue repair and reconstruction can be manufactured using 3-D, and more
recently, 4-D and 5-D printing technologies. The methodology of 3-D printing begins
with the construction of a 3-D model based on 2-D images from CT or MRI. The
printer then utilizes this model to print a 3-D representation by layering thin cross-
sections on top of one another. 3-D printing technology has developed in a signif-
icant manner, and it has found applications in other clinical settings such as the
production of customized patient models, surgical templates, and cutting guides.
More importantly, outstanding precision and accuracy are needed for 3-D printing
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References 81

in order to generate models or representations of true anatomic structures in addi-


tion to providing clinical practicality in dentistry as well as in craniomaxillofacial,
orthopedic, and spinal surgeries.

References

1. Tanaka E, Rodrigo DP, Tanaka M et al (2001) Stress analysis in the TMJ during jaw opening
by use of a three-dimensional finite element model based on magnetic resonance images. Int J
Oral Maxillofac Surg 30:421–430
2. Rho JY, Hobatho MC, Ashman RB (1995) Relations of mechanical properties to density and
CT numbers in human bone. Med Eng Phys 17:347–355
3. Hvid I, Bentzen SM, Linde F et al (1989) X-ray quantitative computed tomography: the relations
to physical properties of proximal tibial trabecular bone specimens. J Biomech 22:837–844
4. Pauwels R, Jacobs R, Singer SR et al (2015) CBCT-based bone quality assessment: are
Hounsfield units applicable? Dentomaxillofac Radiol 44:20140238. https://doi.org/10.1259/
dmfr.20140238
5. Kim DG (2014) Can dental cone beam computed tomography assess bone mineral density? J
Bone Metab 21:117–126
6. Scarfe WC, Farman AG, Sukovic P (2006) Clinical applications of cone-beam computed
tomography in dental practice. J Can Dent Assoc 72:75–80
7. Mah P, Reeves TE, McDavid WD (2010) Deriving Hounsfield units using grey levels in cone
beam computed tomography. Dentomaxillofac Radiol 39:323–335
8. Khan SN, Warkhedkar RM, Shyam AK (2014) Analysis of Hounsfield unit of human bones
for strength evaluation. Procedia Mater Sci 6:512–519
9. Dechow PC, Nail GA, Schwartz-Dabney CL et al (1993) Elastic properties of human
supraorbital and mandibular bone. Am J Phys Anthropol 90:291–306
10. Schwartz-Dabney CL, Dechow PC (2002) Edentulation alters material properties of cortical
bone in the human mandible. J Dent Res 81:613–617
11. Schwartz-Dabney CL, Dechow C (1997) Variations in cortical material properties from
throughout the human mandible. J Dent Res 76:249
12. Keyak JH, Lee IY, Skinner HB (1994) Correlations between orthogonal mechanical properties
and density of trabecular bone: use of different densitometric measures. J Biomed Mater Res
28:1329–1336
13. Galante J, Rostoker W, Ray RD (1970) Physical properties of trabecular bone. Calcif Tissue
Res 5:236–246
14. Schileo E, Dall’ara E, Taddei F et al (2008) An accurate estimation of bone density improves
the accuracy of subject-specific finite element models. J Biomech 41:2483–2491
15. Knowles NK, Reeves JM, Ferreira LM (2016) Quantitative Computed Tomography (QCT)
derived Bone Mineral Density (BMD) in finite element studies: a review of the literature. J
Exp Orthop 3:36. https://doi.org/10.1186/s40634-016-0072-2
16. Gibson LJ (1985) The mechanical behavior of cancellous bone. J Biomech 18:317–328
17. Helgason B, Perilli E, Schileo E et al (2008) Mathematical relationships between bone density
and mechanical properties: a literature review. Clin Biomech 23:135–146
18. Poelert S, Valstar E, Weinans H et al (2013) Patient-specific finite element modeling of bones.
Proc Inst Mech Eng H 227:464–478
19. Hernandez CJ, Beaupré GS, Keller TS et al (2001) The influence of bone volume fraction and
ash fraction on bone strength and modulus. Bone 29:74–78
20. Carter DR, Hayes WC (1977) The compressive behavior of bone as a two-phase porous material.
J Bone Jt Surg 49:954–962
21. Carter DR, Hayes WC (1976) Bone compressive strength: the influence of density and strain
rate. Science 194:1174–1176
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22. Schaffler MB, Burr DB (1988) Stiffness of compact bone: effects of porosity and density. J
Biomech 21:13–16
23. Keller TS (1994) Predicting the compressive mechanical behavior of bone. J Biomech 27:1159–
1168
24. Jacobs C (1994) Numerical simulation of bone adaptation to mechanical loading. Dissertation,
Stanford University
25. Lotz JC, Gerhart TN, Hayes WC (1991) Mechanical properties of metaphyseal bone in the
proximal femur. J Biomech 24:317–329
26. Snyder SM, Schneider E (1991) Estimation of mechanical properties of cortical bone by
computed tomography. J Orthop Res 9:422–431
27. Rice JC, Cowin SC, Bowman JA (1988) On the dependence of the elasticity and strength of
cancellous bone on apparent density. J Biomech 21:155–168
28. Hodgskinson R, Currey JD (1990) The effect of variation in structure on the Young’s modulus
of cancellous bone: a comparison of human and non-human material. Proc Inst Mech Eng H
204:115–121
29. O’Mahony AM, Williams JL, Katz JO et al (2000) Anisotropic elastic properties of cancellous
bone from a human edentulous mandible. Clin Oral Impl Res 11:415–421
30. Kopperdahl DL, Morgan EF, Keaveny TM (2002) Quantitative computed tomography estimates
of the mechanical properties of human vertebral trabecular bone. J Orthop Res 20:801–805
31. Morgan EF, Bayraktar HH, Keaveny TM (2003) Trabecular bone modulus-density relationships
depend on anatomic site. J Biomech 36:897–904
32. Choi AH, Ben-Nissan B (2018) Anatomy, modeling and biomaterial fabrication for dental and
maxillofacial applications. Bentham Science Publishers, United Arab Emirates
33. Choi AH, Conway RC, Taraschi V et al (2015) Biomechanics and functional distortion of the
human mandible. J Investig Clin Dent 6:241–251
34. Choi AH, Ben-Nissan B, Conway RC (2005) Three-dimensional modelling and finite element
analysis of the human mandible during clenching. Aust Dent J 50:42–48
35. Koseki M, Inou N, Maki K (2005) Estimation of masticatory forces for patient-specific analysis
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and biology VI. WIT Transactions on Biomedicine and Health, vol 8. WIT Press, Boston, pp
491–500
36. Choi AH, Matinlinna J, Ben-Nissan B (2013) Effects of micromovement on the changes in
stress distribution of partially stabilized zirconia (PS-ZrO2 ) dental implants and bridge during
clenching: a three-dimensional finite element analysis. Acta Odontol Scand 71:72–81
37. Choi AH, Matinlinna JP, Ben-Nissan B (2012) Finite element stress analysis of Ti-6Al-4V and
partially stabilized zirconia dental implant during clenching. Acta Odontol Scand 70:353–361
www.dentalbooks.co

Chapter 7
Artificial Intelligence, Machine Learning,
and Neural Network

As a field of computer science, artificial intelligence or more commonly known as AI


is conceived with the intention of executing numerous specific tasks that normally
require human intelligence. Fuzzy logic, machine learning, and neural network fall
under the umbrella of AI where algorithms are trained to carry out tasks by studying
patterns from data instead of explicit programming [1]. It has been suggested that the
clinical implications of AI are its ability to predict the survivability of dental implants
as well as offering the opportunity to optimize its design [2]. AI in conjunctions
with numerical simulations could also reduce the computational cost associated with
predicting new bone formation within synthetic bone tissue scaffolds used to treat
large bone defects.

7.1 Fuzzy Logic

Considered as a subcategory of AI, fuzzy logic is a technique of reasoning which


mimic the human behavior of reasoning. As a data handling approach that allows
ambiguity or imprecise descriptions, it acknowledges that in the real world most
things would fall somewhere in between with varying shades of gray [3]. A definite
output which can be partially true or false similar to a human “yes” or “no” decisions
is generated instead of absolutely true or false [3, 4]. Introduced in 1965 by Zadeh
[5], a fuzzy set is a class of objects with a continuum of grades of membership.
Such a set is characterized by a membership function that assigns to each object
a grade of membership ranging between zero and one. The fuzzy “if–then” rules
are a more general concept that plays a vital role in the fuzzy sets approach to
examine imprecise description [6]. Generated from a set of given training patterns,
the classification behavior of the fuzzy “if–then” rule-based classifier can be easily
interpretable by human users as the rules are fundamentally expressed in linguistic
forms [7, 8]. The Mamdani fuzzy rule-based system (implemented as an interpreter

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 83
A. H. Choi, Bone Remodeling and Osseointegration of Implants, Tissue Repair
and Reconstruction, https://doi.org/10.1007/978-981-99-1425-8_7
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84 7 Artificial Intelligence, Machine Learning, and Neural Network

for a set of rules expressed as fuzzy conditional statements) and the Sugeno (Takagi–
Sugeno-Kang) fuzzy rule-based system (has a fuzzy input and its consequence is a
linear input–output relation) are the two main class of fuzzy systems [9, 10]. The
structure of a fuzzy system can be broken down into three blocks. Fuzzification is the
first block that converts the given numbered-input to a linguistic variable utilizing
the membership functions stored within the knowledge base. The inference engine is
the heart of the fuzzy system capable of human decision-making by operating based
on the input data and the fuzzy rules provided. The final block translates the fuzzy
output into a single value (categorical or numerical) [7, 11].
Fuzzy logic mechanobiological modeling is another approach that can be used to
simulate bone healing, in which the mechanical stimulus calculations can be carried
out using finite element analysis (FEA) and the fuzzy rules simulate the mechanobi-
ological regulations [12]. The combination of FEA and a set of fuzzy rules based
on medical knowledge of the fracture healing process to describe tissue transforma-
tion and blood supply such as intramembranous ossification, chondrogenesis, endo-
chondral ossification, and tissue destruction were attempted in a number of studies
[13, 14].
The complex interactions of mechanical stability, revascularization, and tissue
differentiation in secondary fracture healing were examined by Simon and co-
workers through the development of a dynamic model that includes blood perfu-
sion as a spatiotemporal state variable to simulate the revascularization process. A
2-D axisymmetrical finite element (FE) model was based on a standardized callus
geometry of an ovine metatarsus with a transverse osteotomy and loaded axially to
represent the amplitude of the major metatarsal loading during normal walking in
sheep. Each callus element had its own material properties, which were updated at
each time step based on the current tissue concentrations, and the properties of the
pure tissue. Dilatational strain (hydrostatic strain) and distortional strain were the
mechanical stimuli in their study. A Mamdani-type fuzzy logic controller was used
to simulate the biological processes that consisted of eight linguistic “if–then” rules
which described processes of angiogenesis, intramembranous ossification, chondro-
genesis, cartilage calcification, endochondral ossification, and tissue destruction, all
of which depended on local strain state and local blood perfusion. Membership func-
tions, correlating quantitative values such as strain, concentrations, and perfusion, to
linguistic values (such as low, medium, and high), were defined for each of the fuzzy
inputs and the fuzzy output variables. Using the numerical model, the study simu-
lated different healing situations corresponding to previously published experimental
fracture healing cases in sheep and the calculated course of the interfragmentary
movement were compared with weekly measured axial movements [13, 15].
Steiner and co-workers [16] further calibrated the fracture healing algorithm
developed by Simon et al. [15] to be applicable to a greater range of different mechan-
ical conditions, and in particular, predicting fracture healing under axial compres-
sive and torsional rotational isolated loading. In addition, the authors suggested that
the model should also be capable of estimating the healing processes under non-
axially symmetric loading such as translational shear or bending. The local mechan-
ical stimuli (distortional and dilatational strains) were determined in an iterative
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7.1 Fuzzy Logic 85

loop and utilized as input for a fuzzy logic controller along with the current tissue
composition and blood supply. Twenty linguistic fuzzy logic rules control how the
tissue composition and vascularization for each FE within the healing region changes
depending on local mechanical and biological stimuli. The rules were in part based
on a previously published mechano-regulatory model and represent intramembra-
nous ossification, chondrogenesis, endochondral ossification, revascularization, and
tissue destruction. Rules concerning the chondrogenesis process were modified for
an improved representation of the tissue differentiation.
Later, a study adopted from the work of Simon et al. [15] was attempted using
3-D biphasic FEA instead of 2-D model [17]. Biphasic FE model was used to obtain
shear strain and fluid flow in their study, which was then used in their calculations to
determine the biophysical stimulus. According to the authors, it has been previously
suggested that fluid shear strain is the mechanical signals that are sensed by bone cells
and activities of cells regulated in a process known as mechanotransduction. Hence, in
their model, they were able to include this process and examine the way cells sense the
mechanical signals from tissue level and regulate its response. The fuzzy controller
consisted of fourteen linguistic “if–then” rules and was compared to Simon et al.
[15], and more rules were used to describe the processes of angiogenesis, chondro-
genesis, and endochondral ossification. Furthermore, no rule was used to describe the
cartilage calcification, which occurred in the presence of higher mechanical stimuli
and independently from perfusion. The quantitative values of biophysical stimulus,
tissue concentrations, and perfusion were translated to linguistic values through the
membership functions.
Hydrostatic and distortional strains determined from the principal strains within
the healing region were selected as the mechanical stimuli in an effort to gain an
understanding into the spatiotemporal healing phenomena for plated bone regulated
by both FEA and fuzzy logic control [18]. 3-D FE models of femur with a 20 mm
fracture gap in the subtrochanteric region were constructed using a manufacturer
supplied CAD model of the left femur. The callus region representing the initial
fracture hematoma was constructed to capture the tissue composition resulting from
biological tissue characterization. Each callus element contains its own character-
istic material property which was updated after each iteration based on current tissue
concentrations. The callus region was assumed to be full of connective tissues during
the initial stages. The fuzzy controller consisted of nineteen linguistic “if–then” rules
that consider the process of angiogenesis, intramembranous ossification chondro-
genesis, cartilage calcification, endochondral ossification, and bone and cartilage
destruction. Mamdani-type controller was used to link the input variables (mechan-
ical stimuli, perfusion, cartilage, and bone concentration) to predict the changes in
the output variables (perfusion, bone and cartilage concentration).
A fuzzy logic mechano-regulation fracture healing simulation was attempted
and applied to 3-D models representing idealized tibia diaphysis fractures based
on AO/OTA classification of tibial fractures with intramedullary nail fixation and
multiaxial loading conditions [19]. Hydrostatic and distortional strains as mechanical
stimuli determined from FEA using 3-D idealized CAD models of a cortical shaft
with a trabecular bone cylinder were used as inputs for the fuzzy logic controller
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86 7 Artificial Intelligence, Machine Learning, and Neural Network

composed of twenty-four “if–then” rules governing tissue differentiation during the


healing process (intramembranous ossification, endochondral ossification, bone and
cartilage remodeling, cartilage calcification and formation, and tissue destruction).

7.2 Machine Learning and Neural Network

Machine learning centers on the learning aspect of AI through the development of


algorithms based on a wide array of data inputs commonly referred to as covariates.
Machine learning models can account for complex, non-linear relationships due
to their flexibility [20]. Unsupervised, semisupervised, supervised, and reinforce-
ment learning are the four commonly used learning methods in machine learning,
and they are useful for solving different tasks [21]. Furthermore, prognostic models
derived from machine learning can examine and study a vast amount of data and
have shown the capacity to recognize new relationships and associations believed
to be undetectable through human observations [20]. In a recent clinical study, two
different supervised learning methods (a decision tree model and a support vector
machine) were used in an effort to predict the most significant factors in dental
implant prognosis with both methods yielding similar results [22].
Deep learning is a category of machine learning that allows computers to under-
stand the world in terms of a hierarchy of concepts and learn from experience. The
hierarchy of concepts permits the computer to learn complex concepts by building
them out of simpler ones. Furthermore, it is unnecessary for a human computer
operator to specify correctly all the knowledge that the computer requires due to
the fact that the computer collects knowledge from experience [23]. Deep learning
can generate models with exceptional performance because of increasing computer
power, and these models are multilayer artificial neural networks [1].
Inspired by the biological neural networks that make up the human and animal
brain, artificial neural networks (ANNs) are computational analytical tools and are the
most popular AI approach in medicine [3, 24]. The first and simplest type of artificial
neural network conceived was the feedforward neural network, in which there are no
loops or cycles in the network, and as the name suggests, the information can only
move in the forward direction. ANNs consist of layers of neurons, normally an input
layer (where the initial data are inputted for processing), one or two hidden layers
(where the computation is conducted), and a final layer of output neurons (where
the results are generated), and all these layers are fully interconnected. Hence, in
a feedforward neural network, information moves from the input layer through to
the output layer, with the hidden layer in between [25]. “Neurons” are used in the
creation of ANNs, which are networks of highly interconnected computer processors
that are able of conducting parallel computations for knowledge representation and
data processing. Links are used to connect the neurons, and each of these connections
is associated with a numeric number known as weight. In addition, there are also
bias and activation functions. In essence, neurons take the input value and multiply
it by the weight vector. Next, the bias is added to this weighted input. Finally, this
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7.2 Machine Learning and Neural Network 87

summation is further processed by the activation function and an output is produced


[26]. Extensively utilized in neural networks, the backpropagation algorithm is a
learning algorithm in which the weights in the connections are repeatedly attuned so
that the neural network will produce the desired output. In other words, the variations
between the actual output and the desired output are minimized [27].
The capacity of ANN to correctly recognize and categorize patterns has led to
their application in medicine, and in particular solving clinical problems due to their
capability to gain knowledge from historical examples, deal with inexact information,
and evaluate non-linear data [3]. The ability to learn from examples is a vital feature of
ANNs, and hence, the application of ANNs can be categorized into a training phase,
a test phase, and an application phase [28]. The repeated amendments of weights
enable the network to learn [3, 29]. ANNs are rapidly discovering new fields of
application within clinical biomechanics and in particular biomechanical modeling,
where the sequence of input and output variables follow common biomechanical
ideas about movement control without having deterministic relationships of these
variables on hand like electromyogram and force relationship [28].
Deep convolution neural network, which is a type of deep learning, has produced
notable results in prediction and diagnosis in pathology and radiology. In essence, it
is used to process data that contain a grid pattern such as images and is designed to
learn spatial hierarchies of features automatically and adaptively [30]. Constructed
from three types of layers, extractions of features are carried out by the first two layers
of the neural network (convolution and pooling layers). These extracted features are
normally transformed into 1-D arrays of vectors or numbers and then fed as inputs into
the third layer of the network known as a fully connected layer. Learnable weights are
applied to the inputs, and probabilities are predicted for each class in a classification
task [30]. Convolution neural network has also been investigated in dentistry and oral
and maxillofacial surgery due to their ability in object recognition and in handling
complex images such as cone-beam CT (CBCT) images for applications such as
tooth numbering and root morphology [31, 32], dental and maxillofacial radiological
examination [33], diagnosis and detection of cysts and lesions [34, 35], automated
segmentation of the mandibular canals for dental implant planning [36–40], and
bony changes of the temporomandibular joint condyle head [41]. Despite the fact
that CBCT is capable of providing high-quality 3-D images, a study by Minnema et al.
[42] suggested that there are still uncertainties as to which convolution neural network
training strategy is the most ideal for 3-D medical image segmentation. Different
training strategies (2-D, 2.5D, majority voting, randomly oriented 2-D cross-sections,
and 3-D patches) were compared using both simulated and experimental CBCT
images with the intention of providing the most ideal training strategy for CBCT
image segmentation.
It should be mentioned that another well-known model of deep learning is the
recurrent neural network where the connections between nodes can generate a cycle
as in the case of the human brain. This allows a network to recycle its limited compu-
tational resources over time and carry out deeper sequence of non-linear transfor-
mations. Recurrent neural networks are more ideal in tasks which require temporal
patterns to be generated or recognized such as linguistic tasks (speech recognition
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88 7 Artificial Intelligence, Machine Learning, and Neural Network

and text translation) and time series prediction such as drug pharmacokinetics and
pharmacodynamics [43, 44].
It has been postulated that the ability for a machine learning model to study a
function without prior knowledge of the problem and able to map inputs and outputs
will create an opportunity in which finite element method (FEM) can be employed
to generate data that machine learning models can use to calculate a function that
maps inputs such as mechanical properties and outputs such as stresses offline. The
machine learning models can then make predictions for complex biomechanical
behaviors in real time once the mapping functions are fully trained and evaluated [45].
This approach could potentially be useful in easing computational costs associated
with the use of FEM in applications such as design optimization where testing every
possible design scheme is impractical. This is particularly true when it comes to dental
implants in which the stress developed at the bone-implant interface is governed by a
number of design variables such as materials used and the implant geometry [46, 47].
Four research directions have emerged regarding the integration of deep learning
into FEM. These include multiscale simulations, constitutive modeling, element
formulations, and surrogate modeling. Surrogate models are most useful if the FE
model needs to be solved repeatedly because of minor alterations made in the anal-
ysis such as changing boundary conditions. One FE model is substituted by each
surrogate model at the model level. The removal of iterative methods speeds up the
computational process by several orders of magnitude. However, the use of surrogate
models does have its drawbacks. Surrogate models need to be trained specifically for
each problem, and ultimately, this limits their flexibility. In addition, the resources
needed to generate computational data used in the training also need to be considered
[48].
Below are some of the recent examples where FEA is combined with artificial
neural network in applications centered on bone tissue repair and remodeling.

7.3 Predicting the Osseointegration Process

An inverse procedure was first attempted by Deng et al. [49] to identify Young’s
modulus of interfacial tissue around a dental implant using neural network and FEA.
3-D FEA model with known interfacial properties was used to obtain displacement
responses that were then used to train the neural network model. In their study,
perfect bonding was assumed between the dental implant and bone interface; hence,
it cannot describe precisely the property and structure of interfacial bone during the
bone healing process where various degrees of osseointegration and patterns can
take place. Later, the group developed a rapid inverse analysis approach based on the
reduced-basis method (to compute the displacement response of the bone-implant
structure subjected to a harmonic loading) and a trained neural network to iden-
tify “unknown” Young’s modulus of the interfacial tissue between a dental implant
and the surrounding bones. A self-curing resin was used to simulate the changes in
stiffness of the interfacial tissue during the osseointegration process and the authors
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7.4 Design Optimization 89

did not mention at what stage during the curing process the harmonic loading was
applied to the simulated aluminum implant [50]. Although the authors claimed their
proposed approach was able to predict Young’s modulus of the resin with an error
percentage of 2.5%, no other experimental testing was carried out to further vali-
date their inverse analysis approach such as using a different resin. Additionally,
perfect bonding between the bone and implant was assumed in their study and the
ability of this study to identify Young’s modulus of interfacial bone tissue during
the different stages of osseointegration is also unclear. The abovementioned studies
demonstrated the feasibility of combining FEA with machine learning to predict the
outcomes of implants mathematically. In spite of that, they failed to represent real-
istic clinical scenarios or appropriate bone properties. Bone remodeling was also not
considered in their analysis as perfect bonding between the implant and bone tissue
was assumed (100% osseointegration). Furthermore, evaluations of the simulation
outcomes should be carried out against in vivo examinations or clinical trials in order
to determine the validity of the training of the neural network.
It has been postulated that the thickness of soft tissue at the bone-implant inter-
face can be assessed utilizing a method based on the analysis of its ultrasonic
response by means of a simulation-based convolution neural network. Osseointegra-
tion phenomena were determined based on the estimation of the soft tissue thickness
present at the bone-implant interface that was obtained by analyzing the interaction
of the ultrasonic waves with the bone-implant interface. The implant surface rough-
ness was modeled by a sinusoidal function. A number of assumptions were made in
their study including the absence of cancellous bone tissues and the simplification
in the modeling of the bone-implant interface. In addition, their work only demon-
strates the feasibility of such approach to retrieve quantitative information on the
bone-implant interface and was not supported by any experimental studies or clin-
ical trials given the fact that the practical applications of ultrasound techniques in
determining the stability of a dental implant are hindered by the constant changing
variables associated with the osseointegration process [51].

7.4 Design Optimization

As mentioned previously, the clinical success of an implant is largely determined


by the manner in which the mechanical stresses are transferred from implant to the
surrounding bone without generating a force of a magnitude that would jeopardize
the longevity of the implant and prostheses. Carefully planned functional occlusal
loading will result in the preservation of osseointegration and possible increased
bone-to-implant contact. In contrast, insufficient loading may lead to bone destruc-
tion/resorption, while excessive loading may lead to bone loss and/or component
failure. Hence, it is of paramount importance to discover a means of examining,
reducing, and optimizing the stress at the bone-implant interface to reduce the rate
of failure of dental implants [47].
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90 7 Artificial Intelligence, Machine Learning, and Neural Network

It has been postulated that the use of machine learning can be utilized to reduce
the computational cost associated with the application of FEM in determining the
influence of implant design variables such diameter, length, and percentage porosity
on the stresses at the bone-implant interface [52, 53]. A study hypothesized that the
osseointegration process of a dental implant could be improved if it was designed or
selected in such a manner that it possesses specific dimensions and physical features
such as porosity ideal for the patient’s bone conditions and a microstrain value at
the bone-implant interface falls within the range that favors bone growth [53]. An
approach based on 3-D FEA of the human mandible and surrogate models using
artificial neural network was employed to identify the best combination of porosity
and geometry to reach as close as possible to the desired stress (350 MPa for tita-
nium alloy) and microstrain in the bone-implant interface (2500 microstrain) for five
different bone conditions (very strong, strong, normal, weak, and very weak bone).
In their model, all materials were assumed linearly elastic and Young’s modulus was
determined based on CT scan data. The interface between bone and implant was
modeled as fully bonded, simulating the ideal osseointegration scenario and without
any relative motion at the interface. An average biting force of 120 N was applied
on the dental implant.
Later, support vector regression as surrogate models was introduced as a replace-
ment for FEM in a study aimed at reducing the stress magnitude at the bone-implant
interface [52]. A FEA model based on the first molar region of an edentulous mandible
was generated using CT scan data. Both cortical and cancellous bones were simulated
as anisotropic materials and the mechanical properties were selected from previously
published data. The contacts between cortical bone, cancellous bone, and the implant
were modeled as fully bonded. An occlusal force of 150 N was applied vertically to
the upper surface of abutment, which according to the authors, was not suitable to
represent the real chewing cycle.
It should be noted that both studies focused on the reducing the stress at bone-
implant interface as well as attempting to enhance the osseointegration process
through various optimization approaches and algorithms, and no comparisons were
made between their results and predictions with clinical observations of dental
implantations; hence, its translation to the clinical environment will need to be further
investigated.
Mandibular fractures are common facial lesions normally treated with titanium
plates and screws. However, the need for its subsequent removal has led to the use of
absorbable plate and screw systems as an alternative approach in fracture fixation.
Yet, issues such as screw breakage due to high pretension in the screws caused
by incorrect application of insertion torque will need to be addressed. A theoretical
model was attempted to investigate the possibility of using 2-D FE simulation to train
an artificial neural network and its inverse to identify the optimal screw pretension
in absorbable plate and screw systems, which must satisfy a desired maximum von
Mises strain value [54]. In their study, the neural network was used as a surrogated
method to predict the optimal value of maximum von Mises strain by considering the
screw pretension as the design factor. Simplified bone segments were constructed and
used as training for the network. The model assumes that the cortical bone, trabecular
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7.5 Bone Healing and Remodeling 91

bone, absorbable screws, and plates are perfectly bonded to each other. Bone tissues
were considered linearly elastic isotropic material, and the thicknesses of the cortical
bone and trabecular bone were arbitrary set as 2 mm and 13 mm, respectively. An
optimal screw pretension was determined but no validation was carried out in their
study against published data.

7.5 Bone Healing and Remodeling

A multiscale approach was utilized by Hambli and co-workers [55] in an effort


to simulate the bone remodeling process in which 2-D FE was used to calculate
changes only at the macro level of a human proximal femur and a trained 3-D neural
network serving as a numerical substitute for the FE code necessary for the mesoscale
(trabecular architecture) prediction. The application of this multiscale hierarchical
hybrid model based on FEA and neural network enabled a reduction in computational
time. According to the authors, macroscale bone tissue transfers information to the
trabecular network in the form of macroscopic variables and boundary conditions
based on the results of the 2-D FE macroanalysis. This information was then used
by the trained neural network to predict the responses of the trabecular architecture.
Finally, the trabecular network transfers information back to the macroscale bone
tissue in the form of averaged updated material properties. The effective properties
of trabecular bone were modeled as elastic isotropic behavior coupled with damage
incorporating strain and microdamage stimulus. The same approach was later used
in another study to investigate the elastic properties of different bone tissue levels.
3-D FE models for each nanoscopic structure of bone ultrastructure (mineralized
collagen microfibrils, fibrils, and fibers) were proposed. The models were used to
perform parametric studies to examine the influence of geometrical and mechanical
properties of the elementary constituents such as cross-links and hydroxyapatite
crystals on the equivalent properties. These results were then used as training phase
for the neural network. The results were compared and validated using other studies
found in the literature, and the authors claimed that a good agreement was observed
between the simulation outcomes and literature values [56].
Bone adaptation models are frequently solved in the forward direction where
bone response to a given set of loads is calculated through bone tissue adaptation
model. The study by Zadpoor et al. [57] proposed an inverse approach in which an
artificial neural network was used to predict the load that resulted in tissue adaptation
from a given density distribution of trabecular bone. Strain energy density was used
in the tissue adaptation model. 2-D FEA was used to calculate the resulting stress
and strains once the loads were applied, which were then used to determine the
remodeling stimulus signal and the density. The mechanical properties of the bone
tissue were then updated according to the stimulus signal. Linearly varying line load
and a combination of four constant line loads applied on the edges of the geometry
were the loads considered in their analysis. The anisotropic behavior of trabecular
bone was a vital issue the authors stated that it should be implemented if this approach
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92 7 Artificial Intelligence, Machine Learning, and Neural Network

was to be used in a clinical setting. However, despite the originality of such approach,
its practicality in the clinical environment could be confined to applications where
it is important to ascertain the magnitude of physiological load a biomaterial will
experience if used as a bone substitute or tissue engineering scaffold during bone
healing and regeneration process.
It has been suggested that machine learning has considerable potential in
addressing the limitation of the current FE procedures in predicting bone healing
and regeneration around dental implants or in bone tissue engineering scaffolds
at both macroscopic and microscopic levels where existing numerical models are
computationally demanding [58, 59]. The study by Hsu et al. [58] proposed an alter-
native to FE simulations during the design process of dental implants with a work-
flow consisting of a series of machine learning algorithms (deep neural networks).
Mechano-regulatory method was used to generate data of bone healing around dental
implants, and these data were subsequently used to train the deep learning models.
The authors stated that properties such as principal strains and stem cell concentra-
tions of the surrounding bones could be accurately predicted using less time with
the neural network than calculations based on FEM. The authors also claimed that
this level of accuracy was achieved through the development of a tailor-made deep
learning network which permitted the prediction of results 35 days after implant
surgery using only the input data from the first day of implantation. Moreover, the
design guidelines predicted by the network were similar to industry know-hows
without prior knowledge of dental clinics.
In another study, a machine learning-based method to replace the homogenization-
based micro-FE analyses in the conventional multilevel FE framework was proposed
by Wu et al. [59] in an attempt to estimate efficiently and effectively bone remod-
eling inside tissue scaffolds using less computational resources than the conven-
tional approach. The proposed approach was applied to simulate scaffold-based bone
formation in a large segmental defect of an in vivo sheep tibia. Comparisons of the
bone ingrowth results were carried out between those obtained from the conventional
multilevel FE model and the predictions made by the proposed machine learning-
based procedure to examine its efficiency and credibility. A bone remodeling algo-
rithm based on Wolff’s law that considers the strain energy density evaluated at
the microscope level as a mechanical stimulus after sufficient MSC attachment, and
proliferation was adopted to predict bone regeneration outcome at the microstruc-
tural level in the scaffold. Satisfactory accuracy was observed when the authors
compared the machine learning-based time-dependent prediction of bone ingrowth
with conventional multilevel FE model.

7.6 Concluding Remarks

The clinical translation and application of bone healing and remodeling simulations
in areas such as determining the treatment strategies after a fracture or assessing the
suitability of a particular implant design based on the bone quality of the patient is
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References 93

an objective worth pursuing. Currently, FEA is the primary choice when it comes
to simulating and analyzing bone mechanics and structures. However, its depen-
dence on the use of mesh and the accuracy relies on the mesh quality is time and
computationally intensive, thus reducing its clinical practicality and impractical for
scenarios where real-time responses are needed such as minor design changes due to
the anatomical condition of the patient. Studies that utilized AI as a design optimiza-
tion tool have all shown the potential applicability of such approach in improving
design variables to reduce the stresses at the bone-implant interface.
Fuzzy logic and ANN in conjunction with numerical simulations could also reduce
the computational cost associated with predicting osseointegration and new bone
formation. This reduction is achieved through the utilization of FEA to generate
datasets that the AI algorithm can learn from and ultimately makes predictions for
complex bone healing and remodeling process once the algorithm is properly trained
and tested. Furthermore, this approach can be used to carry out inverse calculations
to predict the load that resulted in tissue adaptation from a given density distribution
of bone tissue. This could potentially be beneficial in determining the magnitude
of physiological load a biomaterial will experience if used as a bone substitute or
tissue engineering scaffold during the healing and regeneration process. Neverthe-
less, providing an appropriate learning scheme is vital, as AI (fuzzy logic, machine
learning, or ANN) is heavily reliant on the datasets used in the training phase.

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