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3D Printed Biomaterials for Maxillofacial Tissue Engineering and Reconstruction

– A Review

Article in Open Journal of Biomedical Materials Research · January 2014

DOI: 10.12966/ojbmr.07.02.2014

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Open Journal of Biomedical Materials Research
©Attribution 3.0 Unported (CC BY 3.0)

3D printed biomaterials for maxillofacial tissue engineering and

reconstruction – a review
XingGuo Cheng1*, James J. Yoo2, Robert G. Hale3, Michael R. Davis3, Hyun-Wook Kang2 , Sang Jin
Lee2
1 Microencapsulation and Nanomaterials, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, U.S.A.
2 Wake Forest Institute for Regenerative Medicine, Medical Center Blvd Winston-Salem, NC 27157, Tel: 336-713-7294.
3 US Army Institute of Surgical Research, 3698 Chambers Pass Suite B., Fort Sam Houston, TX, 78234

*Corresponding author (Email: xchengswri@gmail.com)

Abstract The era of 3D printing might bring a revolution to industrial manufacturing. The use of 3D printing technology for
reconstruction of maxillofacial tissues has increased over the past several years. This review represents a summary of recent
developments using the 3D printing technology for maxillofacial tissue engineering and reconstruction. Current limitations,
critical challenges, and future outlook for 3D printed biomaterials for maxillofacial injury are also discussed.
Keywords – 3D printing, biomaterial, bone, skin, maxillofacial, tissue engineering

1. Introduction
3D printing, also known as additive manufacturing
(AM), refers to the manufacturing process of making a
three-dimensional free-form object from a digital model.
Commercial 3D printers, in several different forms,
became more accessible and gained popularity in the last
5 years due to their utility in varied areas, including
architecture, construction, industrial design, automotive,
aerospace, military, fashion, footwear, jewelry, food,
and many other fields. Recently, digital models derived
from medical imaging, such as 3D computed
tomography (CT), surface scanning with
photogrammetry, magnetic resonance imaging (MRI),
angiography and ultra sound (US), have been used to
convert into building code for 3D printing. The printed
objects are useful as medical diagnostic aids, surgical
simulation [1], and prostheses and implants [2].
Maxillofacial injuries differ from other tissue injuries in
that the face is enriched with blood vessels and nerves
and is connected to airways and the cervical spine. The
face covers many important structures, including the
brain, eyes, ears, nose, and mouth. Severe injuries to the
maxillofacial region often pose life-threatening risks.
Treatment options for these injuries should be
considered to ensure satisfactory functional outcomes
(saliva secretion, facial nerve function, hearing, and
vision) and aesthetic results (scarring or contracture
disfiguration). Maxillofacial soft tissue injuries other
than skin (for example, muscle) are usually treated with
regional free flaps with acceptable results [3]. Hard
tissue injuries (for example, underlying craniofacial
skeleton such as mandible and skull injury) generally
require surgery and the placement of implants. The bone
reconstruction is critical to prevent the contraction of
facial soft tissue and maintain normal facial soft tissue
envelope [4]. Facial skin injuries, on the other hand, are
generally treated with current cut-to-fit skin substitutes
or autografts; however, these treatments can lead to
scarring and/or unsatisfactory aesthetic outcome.
Patients with extensive maxillofacial injuries are usually
assessed by 3D imaging modalities, such as CT scan,
which reveals the bone and soft tissue defect. Thus, 3D
printing technology, which can take advantages of
imaging data, is extremely useful in surgical simulation,
planning, or reconstruction.
This review summarizes the properties and performance
of several biomaterials printed via different 3D printing
techniques towards maxillofacial tissue (for example,
facial skin, skull bone and teeth) repair applications. The
limitations, as well as future prospective, are also
discussed.
2. Subjects and Methods
Methods
Using key words “3D print*” and “maxillofacial” in
Scopus for abstracts and articles for all years as of
05/29/2014, a total of 144 documents in English and 4
patents were found. This literature were further
analyzed and reviewed.
Materials used for 3D printing towards maxillofacial
injuries
 Open Journal of Biomedical Materials Research 8

As shown in Table 1, most 3D printed biomaterials for rheological properties, such as shear thinning behavior
maxillofacial injuries are selected from conventional and low-shear stiffness.
(orthopedic) biomaterials, such as collagen/ A
hydroxyapatite or calcium phosphate (CaP) [5], bioglass
[6], biodegradable polymers, such as
poly-lactic-co-glycolic acid (PLGA) [7], or Titanium.
These materials are favorably used due to their proven
biocompatibility and osteoconductivity. Newer
biomaterials, some inspired by nature or new degradable
polymers, were recently explored for 3D printing.
Additionally, photocrosslinked, biocompatible gels, Fig. 1. A) An example of extrusion-based 3D printing
such as Lutrol-F127, have been investigated as scaffolds machine developed at SwRI. B) 3D printed
[8]. The key advantages of a 3D printed scaffold are hydroxyapatite (HA) scaffolds using shear-thinning HA
custom control of shape, porosity, pore connectivity, ink coupled with polyionic interaction. Bar = 200 µm.
material composition, site-specific drug/growth factor Inset shows the printed line spacing , approximately 150
delivery, and orientation. µm.

Table 1. Common 3D printed materials used for 3. Results and Discussion

maxillofacial tissue engineering
Maxillofacial hard tissue repair, regeneration, and
Materials Examples reconstruction
Bioceramics Tricalcium phosphate (TCP), CaP [9, 10], Bone autografting, such as autologous onlay grafts, are
hydroxyapatite (HAP), bioglass [6],
the gold standard for maxillofacial bone repair.
Biopolymer Alginate, Matrigel, Fibrin/, biogenic
Complications include donor site morbidity and
polyphosphate (Bio-PolyP) and biogenic
silica (Bio-Silica)
extended stay in the hospital. Thus, synthetic
Synthetic Polycaprolactone (PCL), PLGA [11], implants/scaffolds become necessary. Both
polymer Lutrol-F127, Perfluorodecalin (PFD), poly biodegradable and non-biodegradable implants are being
(3-hydroxybutyrate-co-3-hydroxyhexanoate) investigated for use in maxillofacial injuries.
(PHBHHx), polyetherketoneketone (PEKK)
[12] In one study, 3D printed synthetic monetite (a type of
Metal Ti [13, 14] CaP) onlay implants were fixed with osteosynthesis
Composite Alginate/Matrigel with BCP, Nano screws on the calvarial bone surface of New Zealand
Material hydroxyapatite/polyamide (n-HA/PA), rabbit. After 8 weeks, integration between the 3D printed
Si-HA/PCL/Demineralized bone matrix monetite implant and the calvarial bone surface and
(DBM), CaP/Collagen, Poly(D,L-lactide) pattern of regeneration within the implants was
and –Tricalciumphosphate [15] observed [18]. Using a similar approach, a bone defect
was created in pig mandible ramus by condyle resection
Critical requirements of ink material developed for for CT and CAD/CAM elaboration of bone volume for
3D printing cutting and scaffold restoration. A perfect-fitting bone
substitute model for rapid prototyped HA scaffolds was
The ink used for 3D printing in the form of liquids, made [5]. Recently, cylindrical 3D printed calcium
semi-solids, or powder must first flow through one or alkaline phosphate granulates scaffolds with graded
more printing nozzles with controlled viscoelastic porosity were produced for bone regeneration of
properties. Once delivered through the nozzle, the ink segmental defects in maxillofacial surgery and dental
should form self-supporting features. This can be implantology [19]. Custom-made 3D printed PLGA
accomplished through different strategies: 1) scaffolds that accurately reconstruct craniomaxillofacial
temperature change leading to solidification of the ink (CMF) bone injuries were also made by a
(for example, melting thermoplastic becomes a solid at positive/negative mold interchange technique [11].
room temperature); 2) solvent evaporation (for example, Poly(D,L-lactide) –Tri calcium phosphate (TCP)
solvent cast printing); 3) UV laser photo crosslinking composite scaffold was printed using selective laser
[16]; 4) a binder to connect particulate matter (glue) melting and proposed for use as an individual bone
[17]; or 5) a gelling mechanism based on crosslinking or substitute implant in cranio-maxillo-facial surgery [15].
a reaction (for example, alginate/Ca ionic crosslinking,
fibrin gel formation). In Figure 1, we have developed Patient specific prosthetics/implants
aqueous, hydroxyapetite (HA) particle inks Based on computed tomography (CT) data, a biomimetic
incorporating polyionic interactions to control n-HA/ polyamide (PA) scaffold, and CAD/CAM for

B
 Open Journal of Biomedical Materials Research
rapid prototyping by three-dimensional (3D) printing, a
perfect-fitting condylar implant was fabricated and
implanted into mandibular condyle defect. It is reported
that the patient ultimately regained reasonable jaw
contour and appearance, as well as appreciable
temporomandibular joint (TMJ) function [20]. More
and more clinical cases have been reported using 3D
printing techniques as a precise, fast, and cheap
maxillofacial or craniofacial defects (e.g., mandible [21,
22], skull [12] ) reconstruction, which aids in shortened
operation time and decreased exposure time to general
anesthesia, decreased blood loss, and shorter wound
exposure time) and easier surgical procedure.
3D printing for facial skin regeneration
Recently, through a joint effort, 3D printing technology
was used towards potential facial skin regeneration.
Custom facemasks made from PCL were fabricated (Fig.
2A-B). The PCL facemasks were further used to deposit
collagen-based wound matrix that can be used as facial
neodermis (Fig. 2C).
A B
C Limitations and future perspective
Fig.2. Use of 3D printing technology for potential
facial skin regeneration. A) Custom 3D printed
facemasks, B) Porosity and filament structure (bar =
2 mm), and C) Electrochemical deposition of
medical-grade collagen facial mask which will be
used as a facial dermis. From left to right: PCL
facemask, Au-coated facemask, and collagen
deposited facemask.
Surgical planning and simulation
A customized titanium plate was configured using a 3D
printing model of mandible as a template before surgery.
Using a 3D printed mandible model reduced the
operation time by 1.5 - 2.5 hours and the shape precision
of the reconstructed mandible was improved [23].
Similarly, other cranial models using 3D printing have
been investigated [24].
Further improvement of 3D printed
scaffolds/implants
Current 3D printing techniques are able to produce
scaffolds with micrometer dimensional precision and/or
reproduce craniomaxillary or bone anatomy (for
example, dimensional error < 5%) [25]. It has been
reported that the mean error was less than 0.3 mm in
construction of a cyno-mandibular condyle model [11].
Various approaches have been used to enhance desired
bioactivities of 3D printed scaffolds for implantation.
These include incorporation of new composition, drugs,
growth factors, and stem cells. Stem cells can either be
directly printed inside or seeded afterwards for
regenerative medicine applications. Growth factors,
such as BMP-2, or drugs can be incorporated inside the
scaffolds for tissue induction [26]. For example, BMP-2
and cells can be incorporated inside scaffolds to
synergistically enhance the bone formation in CaP
ceramic scaffolds [27]. A Bioplotter was used to print
cell-laden bone grafts containing multiple cell types
[28]. 3D cell patterning strategies in tissue engineering
was reviewed [29].
Since 3D printing is dependent upon a digital model
derived from (medical) imaging, the accuracy of 3D
printed scaffolds/implants rely on the resolution of
imaging. Thus, 3D printed prostheses and implants lack
details of the real tissue/defect structure at the
micro/nanoscopic level. Non-conforming rendering was
observed in particular for notches, fissures, grooves,
channels, tuberosities, thin-walled structures, sharp
peaks and crests, teeth, or other specific head regions
[30]. Improvements in both imaging and 3D printing
must be made for high accuracy maxillofacial
reconstruction [31].
The resolution limitation might be overcome partially by
indirect 3D printing. For indirect 3D printing, a negative
mold of the desired structure is printed by a 3D printer
using a sacrificial material. The targeted biomaterial
with refined micro/nano structure is then deposited
inside the negative mold using a conventional scaffold
fabrication process. Once the negative mold is removed,
scaffolds with connected internal channels that are
predefined by the negative mold can be made. Collagen
or collagen with HA scaffold have been made with this
process as well [32].
 Open Journal of Biomedical Materials Research
A training needed. These limitations will be overcome in
B maxillofacial surgeries [22]. The use of 3D printing for
Fig.3. A) Three common ways 3D printing
technology can be applied for maxillofacial tissue
engineering: 1) Printing a model with defects, 2)
Direct printing of defect, and 3) Indirect printing for
implant fabrication by traditional process. B)
Schematic diagram showing scalable fabrication by
printing together with a template architecture.
Another limitation in 3D printed parts is that the
mechanical properties of printed objects do not always
resemble the repaired tissue in terms of modulus,
strength, and in particular, viscoelasticity. Improvement
in mechanical strength often resulted in compromise in
biodegradability or biocompatibility. For example, the
bending strength of sintered, 3D printed CaP/Bioglass
reached 14.9 MPa; however, two new crystal phases of
CaNaPO4 and CaSiO3 appeared after sintering. This
biomechanical inadequacy persists in tissue engineering
scaffolds made by other processes. Improvement in
additive manufacturing process, novel material
development, computational mechanics, and simulation
might overcome this limitation in the future. Other
limitations include relatively high cost and complicate
10
machinery of the 3D printer and special expertise and
time as 3D printers become more accessible and are
more frequently used.
4. Conclusion
In summary, 3D printing technology offers several
advantages for maxillofacial tissue engineering. First,
custom-made scaffolds with precise external
shape/contour and internal pore connectivity can be
made. Second, a wide range of biomaterials from soft to
hard, and biodegradable to nondegradable can be used
and developed either by direct or indirect 3D printing.
Third, 3D printed technology can be used to design and
fabricate tailored, precise fit scaffolds that are promising
for maxillofacial prosthodontics [33], maxillofacial
tissue repair/regeneration and useful aids in most
maxillofacial injuries might be cost-efficient and provide
tremendous benefit to civilian patients suffering from
debilitating injuries. Combat over the past decade in
OIF/ OEF has been characterized by IED (improvised
explosive device) based warfare resulting in unique
patterns of CMF injuries. CMF injuries have been
reported in as high as 42% of all injured DoD service
members. Of the CMF injured, 44% have suffered bony
fractures [34]. The military reconstructive relevance of
3D printing as a facilitating technology for
reconstruction of the CMF bony skeleton therefore is
also significant. Through this emerging technology, a
large number of wounded warriors would benefit.
5. Acknowledgment
The author wishes to acknowledge support from the
Armed Forces Institute of Regenerative Medicine
(Award #W81XWH-13-2-0054) which is awarded and
administered through the U.S. Army Medical Research
Acquisition Activity, 820 Chandler Street, Fort Detrick
MD 21702-5014. The views expressed in this
manuscript do not necessarily reflect the position or the
policy of the Government, and no official endorsement
should be inferred.
The authors also gratefully acknowledge support of this
work from the Southwest Research Institute® (SwRI®)
Internal Research and Development (IR&D) Program
(Project title: Performance-Driven Tissue Engineering
Templates).
 Open Journal of Biomedical Materials Research
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12
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