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Procedia Engineering 00 (2017) 000–000
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Procedia Engineering 200 (2017) 236–243

3rd International Conference on Natural Fibers: Advanced Materials for a Greener World, ICNF
2017, 21-23 June 2017, Braga, Portugal

Biopolymers in Medical Implants: A Brief Review

Rita Rebelo*a, Margarida Fernandesa, Raul Fangueiroa
a
Center for Textile Science and Technology (2C2T), University of Minho, Guimarães, Portugal

Abstract

Biopolymers have been established as a promising class of materials with a wide range of applications, of which
medicine stands out. Characteristics such as biocompatibility, biodegradation and non-cytotoxicity make these
material excellent candidates to be used in implantable materials. This review examines the main properties of
biopolymers, as well as the potential of different biopolymers, including polylactic acid (PLA), silk and chitosan, for
application in implantable medical devices.

© 2017 The Authors. Published by Elsevier Ltd.

Peer-review under responsibility of the scientific committee of the 3rd International Conference on Natural Fibers: Advanced
Materials for a Greener World.

Keywords: Biopolymers; Medical implants;PLA; Silk; Chitosan.

1. Introduction

The main objective of implantable devices is to mimic a body part and are used to replace a damaged organ or
structure to sustain normal body function. Some of the most used medical implants consist of heart, bones, eyes,
ears, knees, breasts, hips and cardiovascular system implants [1]. Traditional materials like metals, ceramics and
synthetic polymers have been applied but they present some disadvantages, like immunological rejection by the
body [2–4]. Furthermore, synthetic polymers may present concerns about their biodegradation products in the body,
which may lead to an unwanted immunogenic response. The degradation process occurs by hydrolysis, producing

* Corresponding author. Tel.: +351-934309589.

E-mail address: ritanogueirar@gmail.com

1877-7058 © 2017 The Authors. Published by Elsevier Ltd.

Peer-review under responsibility of the scientific committee of the 3rd International Conference on Natural Fibers: Advanced Materials for a
Greener World.

1877-7058 © 2017 The Authors. Published by Elsevier Ltd.

Peer-review under responsibility of the scientific committee of the 3rd International Conference on Natural Fibers: Advanced
Materials for a Greener World
10.1016/j.proeng.2017.07.034
 Rita Rebelo et al. / Procedia Engineering 200 (2017) 236–243 237
Author name / Procedia Engineering 00 (2017) 000–000 2

carbon dioxide, which lowers the local pH resulting in cell and tissue necrosis [5]. This way, biopolymers assume a
major role among materials for medical implantation.
Biopolymers are polymers produced by living organisms and can be derived from microbial systems, extracted
from plants, or chemically synthesized from basic biological systems. They present some advantages when
compared to synthetic polymers, namely a well-defined, and more complex, structure, degradability and
renewability [6–8]. Biopolymers have been developed for use as medical materials, packaging, cosmetics, food
additives, clothing fabrics, water treatment chemicals, industrial plastics, absorbents, biosensors, and even data
storage elements. There are three main groups of biopolymers: polysaccharides, proteins and polynucleotics and
their classification is given in Table 1 [9].

Table 1. Classification of biopolymers.

Classification Origin Biopolymers
Starch (amylose/amylopectin), Cellulose, Agar, Alginate, Carrageenan, Pectin,
Plant/algal
Konjac, Various gums (e.g., guar)
Animal Chitin/chitosan, Hyaluronic acid
Polysaccharides Xanthan, Dextran, GelIan, Levan, CurdIan, Polygalactosamine
Bacterial
Cellulose (bacterial)
Fungal Pullulan, Elsinan, Yeast glucans
Lipids/surfactants Acetoglycerides, waxes, surfactants, Emulsan
Silks, Collagen/gelatina, Elastin, Resilin, Adhesives, Polyamino acids, Soy, zein,
Proteins
wheat gluten, casein,Serum albumin
Polyesters Polyhydroxyalkanoates, Polylactic acid

Shellac, Poly-gamma-glutamic acid, Natural rubber, Synthetic polymers from

Specialty polymers
natural fats and oils, nylon from castor oil

Biopolymers, whose degradation products are not immunogenic, have a great potential to be used in the
development of therapeutic devices such as temporary prostheses, three-dimensional porous structures as scaffolds
for tissue engineering, and as controlled/ sustained release drug delivery vehicles and applications like suturing,
fixation or adhesion [8–10]. This review will be mainly focused on the development of implantable devices made of
polylactic acid (PLA), silk and chitosan.

1.1. PLA

PLA (Figure 1) is one of the most promising biodegradable polymers and it can be derived from natural
feedstock such as corn starch rice, potatoes and other natural resources. The mechanical properties of PLA are
similar to synthetic polymers like polypropylene, and has the advantage of higher abundance and lower cost [11].
Furthermore, PLA is bioabsorbable and this characteristic may offer some benefits when applied to implantable
devices. In the case of stents, for example, after serving as an intravascular dilator it may biodegrade by the human
body fluids and no foreign body will remain, avoid a second surgery for stent removal. Tamai et al. [12] developed
PLA-based biodegradable stents and achieved promising results after application in human models. Another
research has studied the biodegradation of PLA stents in rabbit aortas and concluded that it performed quite well
[13]. Additionally, the study determined that PLA stents were as hemocompatible as stain steel stents and PLA
stents allowed the measurements of luminal patency in magnetic resonance imaging, in contrast to the stain steel
stents.
Chang et al. [14] prepared a novel porous PLA composite scaffold and evaluated its capacity as a carrier for the
recombinant bone morphogenetic protein 2 (rhBMP2), showing a sufficient capability of carrying the protein,
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inducing bone formation in two weeks. Zhang et al. [15] developed nanocomposites of
PLA/octadecylaminefunctionalized nano-diamond (ND-ODA) for use in tissue engineering, reporting the improved
mechanical properties (Young’s modulus and hardness), when compared to PLA, due to the good affinity between
the polymer and the filler in the composites, as well as biocompatibility and non-cytotoxicity, indicating the
applicability of this composite for tissue engineering.
Devices made of PLA-PGA (polyglycolic acid) copolymers have been used for implantable in orthopedic
applications. Compression-molded copolymers have been used as plates or screws for the treatment of fractures and
to fill in bone defects. The materials have also been used as scaffolding to facilitate the formation of new cartilage
material in the body. Copolymers of PLA and PGA are more useful than homopolymers of PLA and PGA because
their rate of degradation can be adjusted according the final applications, besides their biocompatibility and
nontoxicity [9,16].
Fangueiro et al. [17] has patented a technology for the production of braided corrugated vascular prosthesis
made of PLA and polyethylene terephthalate (PET) that re-establishes blood flow in damaged segments of a blood
vessel, and is particularly useful in vascular surgery (Figure 2A). These two biocompatible yarns were used to
obtain a structures in which PLA may be absorbed by the human body while the other provide mechanical support.
Fangueiro’s group also possess wide experience on the development of ligaments made of PLA, PGA and PDO
(Figure 2B).

Figure 1. Chemical structure of PLA.

Figure 2. Implantable devices made by braiding technology. A) Braided vascular prosthesis as a medical device for blood vessel [17] and B)
PLA-based mimicking ligament [18].

1.2. Silk

Another biopolymer commonly used in implantable devices is silk. The raw silk thread produced by a silkworm
is composed of fibroid in the core, silk fibroin, and a glue-like coating consisting of sericin proteins.
More recent studies with well-defined silkworm silk fibers and films suggest that the core silk fibroin fibers
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exhibit comparable in vitro and in vivo biocompatibility with other commonly used biomaterials such as polylactic
acid and collagen, besides possessing high mechanical resistance. This is mainly due to the -sheet structure of silk
fibroin, in which strong hydrogen bonds (inter- and intra-chain) and van der Waals interactions generate a structure
that is thermodynamically stable (Figure 3). Altman et al. [19] have studied the development of a wire rope matrix
for the development of autologous tissue engineered anterior cruciate ligaments (ACL) using a patient’s own adult
stem cells with silk. Also, Zhang [20] found that the materials modified with sericin and sericin composites are
useful as degradable biomaterials, biomedical materials, functional membranes, fibers, and fabrics.
Meinel and Kaplan [21] studied the potential use of silk fibroin in musculoskeletal system. Silk fibroin has the
versatility for scaffolding and, in addition, present advanced mechanical properties and good stabilization as well as
controlled delivery of entrapped protein and small molecule drugs. Moreover, new delivery platforms have been
reported, as drug delivery from microneedles, using silk fibroin-protein drug bioconjugates, or silk fibroin
functionalized scaffolds with tailored surface charge to fine-tune protein drug delivery in a biomimetic fashion.
Thus, the promising advances in drug delivery/biomaterial interface is expected to lead into future studies with
relevant results for the use of these biopolymers in musculosketal diseases.
Franck et al. [22] studied the potential of gel spun silk scaffolds in bladder tissue engineering and determined the
effect of different extracellular matrix protein coatings on the ability of silk matrices to support cell responses. As
main conclusions, they reported that structural morphology and the presence of specific tissue-specific proteins
coatings were found to be significant factors in the performance of silk biomaterials. A combination of fibronectin
coatings with silk scaffold was reported as the highest level of primary smooth muscle cells and urothelial cell
attachment as well as supported their respective differentiated phenotypes.
More recently, Park et al. [23] reported a new all-aqueous process for the production of three-dimensional
porous silk fibroin scaffolds. The fabricated scaffolds showed fair hydrophilicity and outstanding mechanical
properties, namely their compressive strength and compressive modulus, when compared to those previous reported.
Additionally, fabricated scaffolds provided positive conditions for the growth of human chondrocytes, increasing
cells attachment and proliferation. The use of this new technique is a promising process to the use of biomaterials.

Figure 3. Silk fibroin -sheet crystals.

1.3. Chitosan

Finally, chitosan is a biopolymer that has been widely used in medical applications. Chitosan is a cationic
polysaccharide produced by deacetylation of chitin, a polysaccharide found in the exoskeleton of crustaceans,
obtained from an alkalizing process at high temperatures (Figure 4) [16]. Widely know for its antimicrobial
properties, this biopolymer is also a biodegradable and biocompatible natural polymer that has been widely used in
different forms (gels, films, particles, membranes or scaffolds) in a large number of applications, ranging from
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biomedical to industrial areas [24]. Furthermore, due to its characteristics, chitosan has an important role in cell
attachment and growth, and it is vastly used as matrix in tissue engineering [25–27], once it can be fabricated in
porous structures [28].

Figure 4. Schematic representation of chitosan chemical structure.

The main application of chitosan in implants are: bone, ligament, cartilage, tendon, liver, neural, stents and skin
regeneration. Meng et al. [29] used a coating of chitosan and heparin to promote the acceleration of re-
endothelization and healing process after coronary stent implementation in a porcine iliac artery. The results showed
that the coating could promote endothelial cell compatibility and hemocompatibility to the stent surface. Moreover,
Chen et al. [30] developed a polymeric stent, made from chitosan-based films fixed by genipin, in order to increase
the mechanical properties. The results showed not only an improvement in the mechanical behavior, but also a re-
endothelization of the stent-implanted vessel.
Several examples of chitosan-based matrices have been reported to bone applications. Once chitosan matrices,
per si, are mechanically weak, the need to combine chitosan with another materials have been raised, in order to
serve as osteoconductive matrices. Li et al. [31] developed a chitosan-alginate scaffold and an increase in the
mechanical strength of the scaffold was observed, due to the strong ionic interaction between chitosan and alginate.
In Table 2 are present several applications of chitosan in different medical fields.

Table 2. Chitosan implants: applications in various medical fields.

Field of application Implants for References
Cardiology Heart valves- electrospun [32]
gelatin-chitosan-polyurethane

Dermatology Gelatin/chitosan/hyaluronan [33]

scaffold for
skin regeneration

Surgery Nerve regeneration— [34]

chitosan/gelatin
scaffolds

Liver—chitosan/gelatin [35]
scaffold
Ophthalmology Contact lens— [36]
chitosan/gelatin

On account of biopolymer properties like biocompatibility, non-toxicity and biodegradability, their application in
implantable devices is rapidly expanding with huge potentialities. In table 3 are presented the main mechanical and
thermal properties of the biopolymers.
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Table 3. Mechanical and thermal properties of biopolymers [9].

Material σB (MPa)a ϵB (%)b Tgc Tmd
Tendon Chitosan 56.5-79.3 11.9-14.7
B. Mori silk 740 20
Spider Silk 875-972 17-18
PLLA 28-50 6 50-65 170-190
DL-PLA 29-35 6 50-53 Amorphous
a: Tensile strength, b: Elongation-at-break, c: Glass temperature, d: Melting temperature.

2. Conclusions

Currently, the use of biopolymers such as PLA, silk and chitosan have been increasingly researched for medical
applications. The inherent properties of biopolymers, like biocompatibility and biodegradability, provide great
advantages and increase their potential use in implantable medical applications. These new materials have great
importance in medicine, since synthetic materials do not fulfil the needs for living systems. This way, recent studies
have proven that the use of biopolymers, when combined with synthetic materials, have the possibility to
revolutionize the medical field.

Acknowledgements

This work is financed by FEDER funds through the Competitivity Factors Operational Programme - COMPETE
and by national funds through FCT – Foundation for Science and Technology within the scope of the project POCI-
01-0145-FEDER-007136

References

[1] R. Bhatt, M. Jaffe, Biopolymers in Medical Implants, in: A.S. Narang, S.H. Boddu (Eds.), Excip. Appl.
Formul. Des. Drug Deliv., Springer, 2015: pp. 311–348.
[2] L. Lu, S.J. Peter, M.D. Lyman, H. Lai, S.M. Leite, J.A. Tamada, et al., In vitro and in vivo degradation of
porous poly ( DL -lactic- co -glycolic acid ) foams, Biomaterials. 21 (2000) 1837–1845.
[3] S.H. Oh, S. Gon, E. Seok, S. Ho, J. Ho, Fabrication and characterization of hydrophilic poly ( lactic- co -
glycolic acid )/ poly ( vinyl alcohol ) blend cell scaffolds by melt-molding particulate-leaching method,
Biomaterials. 24 (2003) 4011–4021.
[4] A.S. Rowlands, S.A. Lim, D. Martin, J.J. Cooper-White, Polyurethane / poly ( lactic- co -glycolic ) acid
composite scaffolds fabricated by thermally induced phase separation, Biomaterials. 28 (2007) 2109–2121.
[5] H. Liu, E.B. Slamovich, T.J. Webster, Less harmful acidic degradation of poly ( lactic- co-glycolic acid )
bone tissue engineering scaffolds through titania nanoparticle addition, Int. J. Nanomedicine. 4 (2006) 541–
545.
[6] F.A. Cziple, A.J. Marques, Biopolymers Versus Synthetic Polymers, Anul XV. 1 (2008) 125–132.
[7] R. Augustine, R. Rajakumari, M. Mozeti, A. George, Biopolymers for Health , Food , and Cosmetic
Applications, Wiley, 2013.
[8] M. Niaounakis, Biopolymers: Applications and Trends, Elsevier, 2015.
[9] N. Onar, Usage Of Biopolymers In Medical Applications, in: Proc. 3rd Indo-Czech Text. Res. Conf., 2014.
[10] N. Reddy, R. Reddy, Q. Jiang, Crosslinking biopolymers for biomedical applications, Trends Biotechnol. 33
(2015) 362–369.
[11] T. Mukherjee, N. Kao, PLA Based Biopolymer Reinforced with Natural Fibre : A Review, J. Polym.
Environ. 19 (2011) 714–725.
[12] H. Tamai, K. Igaki, E. Kyo, K. Kosuga, A. Kawashima, S. Matsui, et al., Initial and 6-Month Results of
Biodegradable Poly-l-Lactic Acid Coronary Stents in Humans, Circulation. 102 (2000) 399–404.
242 Rita Rebelo et al. / Procedia Engineering 200 (2017) 236–243
Author name / Procedia Engineering 00 (2017) 000–000 7

[13] E. Hietala, Poly-L / D-lactide stents as intravascular devices – an experimental study, Tampere University of
Technology, 2004.
[14] P. Chang, B. Liu, C. Liu, H. Chou, M. Ho, H. Liu, et al., Bone tissue engineering with novel rhBMP2-PLLA
composite scaffolds, J. Biomed. Mater. Res. Part A. 81 (2007) 771–780.
[15] Q. Zhang, V.N. Mochalin, I. Neitzel, I.Y. Knoke, J. Han, C.A. Klug, et al., Fluorescent PLLA-nanodiamond
composites for bone tissue engineering, Biomaterials. 32 (2011) 87–94.
[16] R. Rebelo, N. Vila, R. Fangueiro, Poly Lactic Acid Fibre Based Biodegradable Stents and Their
Fumctionalization Techniques, in: R. Fangueiro, S. Rana (Eds.), Nat. Fibres Adv. Sci. Technol. Towar. Ind.
Appl. From Sci. to Mark., RILEM Bookseries, 2016: pp. 331–342.
[17] R. Fangueiro, J. Carrilho, L. Antoniassi, P. Pina, Braided corrugated textile vascular prosthesis and process
of producing same-WO2009141715A3, 2009.
[18] J. Cruz, S. Rana, R. Fangueiro, R. Guedes, Designing artificial anterior cruciate ligaments based on novel
fibrous structures, Fibers Polym. 15 (2014) 181–186.
[19] G.H. Altman, F. Diaz, C. Jakuba, T. Calabro, R.L. Horan, J. Chen, et al., Silk-based biomaterials,
Biomaterials. 24 (2003) 401–416.
[20] Y. Zhang, Applications of natural silk protein sericin in biomaterials, Biotechnol. Adv. 20 (2002) 91–100.
[21] L. Meinel, D.L. Kaplan, Silk constructs for delivery of muskuloskeletal therapeutics, Adv. Drug Deliv. Rev.
64 (2012) 1111–1122.
[22] D. Franck, E.S. Gil, R.M. Adam, D.L. Kaplan, Y.G. Chung, C.R.E. Jr, et al., Evaluation of Silk Biomaterials
in Combination with Extracellular Matrix Coatings for Bladder Tissue Engineering with Primary and
Pluripotent Cells, PLoS One. 8 (2013) e56337.
[23] J.K. Park, J. Shim, K.S. Kang, J. Yeom, H.S. Jung, J.Y. Kim, et al., Solid Free-Form Fabrication of Tissue-
Engineering Scaffolds with a Poly ( lactic-co-glycolic acid ) Grafted Hyaluronic Acid Conjugate
Encapsulating an Intact Bone Morphogenetic Protein – 2 / Poly ( ethylene glycol ) Complex, Adv. Funct.
Mater. 21 (2011) 2906–2912.
[24] V. Balan, L. Verestiuc, Strategies to improve chitosan hemocompatibility : A review, Eur. Polym. J. 53
(2014) 171–188.
[25] S. Meng, Z. Liu, W. Zhong, Q. Wang, Q. Du, Phosphorylcholine modified chitosan : Appetent and safe
material for cells, Carbohydr. Polym. 70 (2007) 82–88.
[26] Y. Zhu, C. Gao, X. Liu, T. ao He, J. Shen, Immobilization of Biomacromolecules onto Aminolyzed Poly ( L
-lactic acid ) toward Acceleration of Endothelium Regeneration, Tissue Eng. 10 (2004).
[27] R.L. Reis, N.M. Neves, J.F. Mano, M.E. Gomes, A.P. Marques, H.S. Azevedo, Natural-Based Polymers for
Biomedical Applications, Woodhead Publishing Limited, 2008.
[28] S. V. Madihally, H.W.T. Matthew, Porous chitosan scaffolds for tissue engineering, Biomaterials. 20 (1999)
1133–1142.
[29] S. Meng, Z. Liu, L. Shen, Z. Guo, L.L. Chou, W. Zhong, The effect of a layer-by-layer chitosan – heparin
coating on the endothelialization and coagulation properties of a coronary stent system, Biomaterials. 30
(2009) 2276–2283.
[30] M. Chen, C. Liu, H. Tsai, W. Lai, Y. Chang, H. Sung, Mechanical properties , drug eluting characteristics
and in vivo performance of a genipin-crosslinked chitosan polymeric stent, Biomaterials. 30 (2009) 5560–
5571.
[31] Z. Li, H.R. Ramay, K.D. Hauch, D. Xiao, M. Zhang, Chitosan–alginate hybrid scaffolds for bone tissue
engineering, Biomaterials. (2005) 3919–3928.
[32] C. Wong, BIOMIMETIC ELECTROSPUN GELATIN – CHITOSAN POLYURETHANE FOR HEART
VALVE LEAFLETS, J. Mech. Med. Biol. 10 (2010) 563.
[33] J. Enrione, F. Osorio, D. López, C. Weinstein-Oppenheimer, M.A. Fuentes, R. Ceriani, et al.,
Characterization of a Gelatin / Chitosan / Hyaluronan scaffold- polymer, Electron. J. Biotechnol. 13 (2010)
20–21.
[34] V. Chiono, E. Pulieri, G. Vozzi, G. Ciardelli, A. Ahluwalia, P. Giusti, Genipin - crosslinked chitosan /
gelatin blends for biomedical applications, J. Mater. Med. 19 (2008) 889–898.
[35] H. Jiankang, L. Dichen, L. Yaxiong, Y. Bo, Z. Hanxiang, L. Qin, et al., Preparation of chitosan – gelatin
 Rita Rebelo et al. / Procedia Engineering 200 (2017) 236–243 243
Author name / Procedia Engineering 00 (2017) 000–000 8

hybrid scaffolds with well-organized microstructures for hepatic tissue engineering, Acta Biomater. 5 (2009)
453–461.
[36] S. Xin-yuan, T. Tian-wei, New Contact Lens Based on Chitosan/Gelatin Composites, J. Compat. Polym. 19
(2004) 467–479.