Abstract
Scaffolds play a crucial role in tissue engineering. Biodegradable polymers with great processing flexibility are the predominant scaffolding materials. Synthetic biodegradable polymers with well-defined structure and without immunological concerns associated with naturally derived polymers are widely used in tissue engineering. The synthetic biodegradable polymers that are widely used in tissue engineering, including polyesters, polyanhydrides, polyphosphazenes, polyurethane, and poly (glycerol sebacate) are summarized in this article. New developments in conducting polymers, photoresponsive polymers, amino-acid-based polymers, enzymatically degradable polymers, and peptide-activated polymers are also discussed. In addition to chemical functionalization, the scaffold designs that mimic the nano and micro features of the extracellular matrix (ECM) are presented as well, and composite and nanocomposite scaffolds are also reviewed.
Similar content being viewed by others
References
Couch N, Wtlson R, Hager E, Murray J. Transplantatton of cadaver kidneys experience with 21 cases. Surgery, 1966, 59: 183–188
Langer R, Vacanti JP. Tissue engineering. Science, 1993, 260: 920–926
Guo BL, Glavas L, Albertsson AC. Biodegradable and electrically conducting polymers for biomedical applications. Prog Polym Sci, 2013, 38: 1263–1286
Ma PX. Biomimetic materials for tissue engineering. Adv Drug Delivery Rev, 2008, 60: 184–198
Liu XH, Holzwarth JM, Ma PX. Functionalized synthetic biodegradable polymer scaffolds for tissue engineering. Macromol Biosci, 2012, 12: 911–919
Chen GP, Ushida T, Tateishi T. Scaffold design for tissue engineering. Macromol Biosci, 2002, 2: 67–77
Yang SF, Leong KF, Du ZH, Chua CK. The design of scaffolds for use in tissue engineering. Part 1. Traditional factors. Tissue Eng, 2001, 7: 679–689
Holzwarth JM, Ma PX. 3D nanofibrous scaffolds for tissue engineering. J Mater Chem, 2011, 21: 10243–10251
Nair LS, Laurencin CT. Biodegradable polymers as biomaterials. Prog Polym Sci, 2007, 32: 762–798
Tian HY, Tang ZH, Zhuang XL, Chen XS, Jing XB. Biodegradable synthetic polymers: preparation, functionalization and biomedical application. Prog Polym Sci, 2012, 37: 237–280
Van Vlierberghe S, Dubruel P, Schacht E. Biopolymer-based hydrogels as scaffolds for tissue engineering applications: a review. Biomacromolecules, 2011, 12: 1387–1408
Tate MLK, Falls TD, McBride SH, Atit R, Knothe UR. Mechanical modulation of osteochondroprogenitor cell fate. Int J Biochem Cell Biol, 2008, 40: 2720–2738
Magnusson JP, Saeed AO, Fernandez-Trillo F, Alexander C. Synthetic polymers for biopharmaceutical delivery. Polym Chem, 2011, 2: 48–59
Cameron DJA, Shaver MP. Aliphatic polyester polymer stars: synthesis, properties and applications in biomedicine and nanotechnology. Chem Soc Rev, 2011, 40: 1761–1776
Hakkarainen M, Albertsson AC. Degradation products of aliphatic and aliphatic-aromatic polyesters. Adv Polym Sci, 2008, 211: 85–116
Jerome C, Lecomte P. Recent advances in the synthesis of aliphatic polyesters by ring-opening polymerization. Adv Drug Delivery Rev, 2008, 60: 1056–1076
Seyednejad H, Ghassemi AH, van Nostrum CF, Vermonden T, Hennink WE. Functional aliphatic polyesters for biomedical and pharmaceutical applications. J Controlled Release, 2011, 152: 168–176
Gupta B, Revagade N, Hilborn J. Poly(lactic acid) fiber: an overview. Prog Polym Sci, 2007, 32: 455–482
Liu XH, Ma PX. The nanofibrous architecture of poly(l-lactic acid)-based functional copolymers. Biomaterials, 2010, 31: 259–269
Labet M, Thielemans W. Synthesis of polycaprolactone: a review. Chem Soc Rev, 2009, 38: 3484–3504
Woodruff MA, Hutmacher DW. The return of a forgotten polymer-Polycaprolactone in the 21st century. Prog Polym Sci, 2010, 351: 1217–1256
Chang LL, Liu JJ, Zhang JH, Deng LD, Dong AJ. pH-sensitive nanoparticles prepared from amphiphilic and biodegradable methoxy poly(ethylene glycol)-block-(polycaprolactone-graft-poly (methacrylic acid)) for oral drug delivery. Polym Chem, 2013, 4: 1430–1438
McNeil SE, Griffiths HR, Perrie Y. Polycaprolactone fibres as a potential delivery system for collagen to support bone regeneration. Curr Drug Deliv, 2011, 8: 448–455
Torres MP, Vogel BM, Narasimhan B, Mallapragada SK. Synthesis and characterization of novel polyanhydrides with tailored erosion mechanisms. J Biomed Mater Res A, 2006, 76A: 102–110
Jain JP, Chitkara D, Kumar N. Polyanhydrides as localized drug delivery carrier: an update. Expert Opin Drug Deliv, 2008, 5: 889–907
Jain JP, Modi S, Domb AJ, Kumar N. Role of polyanhydrides as localized drug carriers. J Controlled Release, 2005, 103: 541–563
Allcock HR. Generation of structural diversity in polyphosphazenes. Appl Organomet Chem, 2013, 27: 620–629
Ding JH, Wang L, Yu HJ, Yang QA, Deng LB. Progress in synthesis of polyphosphazenes. Des Monomers Polym, 2008, 11: 215–222
Teasdale I, Bruggemann O. Polyphosphazenes: multifunctional, biodegradable vehicles for drug and gene delivery. Polymers, 2013, 5: 161–187
Krogman NR, Weikel AL, Kristhart KA, Nukavarapu SP, Deng M, Nair LS, Laurencin CT, Allcock HR. The influence of side group modification in polyphosphazenes on hydrolysis and cell adhesion of blends with PLGA. Biomaterials, 2009, 30: 3035–3041
Nichol JL, Morozowich NL, Allcock HR. Biodegradable alanine and phenylalanine alkyl ester polyphosphazenes as potential ligament and tendon tissue scaffolds. Polym Chem, 2013, 4: 600–606
Krol P. Synthesis methods, chemical structures and phase structures of linear polyurethanes. Properties and applications of linear polyurethanes in polyurethane elastomers, copolymers and ionomers. Prog Mater Sci, 2007, 52: 915–1015
Santerre JP, Woodhouse K, Laroche G, Labow RS. Understanding the biodegradation of polyurethanes: from classical implants to tissue engineering materials. Biomaterials, 2005, 26: 7457–7470
Guelcher SA. Biodegradable polyurethanes: synthesis and applications in regenerative medicine. Tissue Eng Part B Rev, 2008, 14: 3–17
Zhang JY, Doll BA, Beckman EJ, Hollinger JO. Three-dimensional biocompatible ascorbic acid-containing scaffold for bone tissue engineering. Tissue Eng, 2003, 9: 1143–1157
Rai R, Tallawi M, Grigore A, Boccaccini AR. Synthesis, properties and biomedical applications of poly(glycerol sebacate) (PGS): a review. Prog Polym Sci, 2012, 37: 1051–1078
Wang YD, Ameer GA, Sheppard BJ, Langer R. A tough biodegradable elastomer. Nat Biotechnol, 2002, 20: 602–606
Pomerantseva I, Krebs N, Hart A, Neville CM, Huang AY, Sundback CA. Degradation behavior of poly(glycerol sebacate). J Biomed Mater Res A, 2009, 91A: 1038–1047
Patel A, Gaharwar AK, Iviglia G, Zhang HB, Mukundan S, Mihaila SM, Demarchi D, Khademhosseini A. Highly elastomeric poly (glycerol sebacate)-co-poly(ethylene glycol) amphiphilic block copolymers. Biomaterials, 2013, 34: 3970–3983
Masoumi N, Johnson KL, Howell MC, Engelmayr GC. Valvular interstitial cell seeded poly(glycerol sebacate) scaffolds: toward a biomimetic in vitro model for heart valve tissue engineering. Acta Biomater, 2013, 9: 5974–5988
Ravichandran R, Venugopal JR, Sundarrajan S, Mukherjee S, Ramakrishna S. Poly(glycerol sebacate)/gelatin core/shell fibrous structure for regeneration of myocardial infarction. Tissue Eng Part A, 2011, 17: 1363–1373
Sun ZJ, Chen C, Sun MZ, Ai CH, Lu XL, Zheng YF, Yang BF, Dong DL. The application of poly(glycerol-sebacate) as biodegradable drug carrier. Biomaterials, 2009, 30: 5209–5214
Slaughter BV, Khurshid SS, Fisher OZ, Khademhosseini A, Peppas NA. Hydrogels in regenerative medicine. Adv Mater, 2009, 21: 3307–3329
Nouailhas H, Li F, El Ghzaoui A, Li SM, Coudane J. Influence of racemization on stereocomplex-induced gelation of water-soluble polylactide-poly(ethylene glycol) block copolymers. Polym Int, 2010, 59: 1077–1083
Peyton SR, Raub CB, Keschrumrus VP, Putnam AJ. The use of poly(ethylene glycol) hydrogels to investigate the impact of ECM chemistry and mechanics on smooth muscle cells. Biomaterials, 2006, 27: 4881–4893
Mann BK, JL. W. Cell adhesion peptides alter smooth muscle cell adhesion, proliferation, migration, and matrix protein synthesis on modified surfaces and in polymer scaffolds. J Biomed Mater Res A, 2002, 60: 86–93
Abebe DG, Fujiwara T. Controlled thermoresponsive hydrogels by stereocomplexed PLA-PEG-PLA prepared via hybrid micelles of pre-mixed copolymers with different PEG lengths. Biomacromolecules, 2012, 13: 1828–1836
Buwalda SJ, Calucci L, Forte C, Dijkstra PJ, Feijen J. Stereocomplexed 8-armed poly(ethylene glycol)-poly(lactide) star block copolymer hydrogels: gelation mechanism, mechanical properties and degradation behavior. Polymer, 2012, 53: 2809–2817
Yang JY, Jacobsen MT, Pan HZ, Kopecek J. Synthesis and characterization of enzymatically degradable PEG-based peptide-containing hydrogels. Macromol Biosci, 2010, 10: 445–454
Lutolf MP, Lauer-Fields JL, Schmoekel HG, Metters AT, Weber FE, Fields GB, Hubbell JA. Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: engineering cell-invasion characteristics. Proc Natl Acad Sci USA, 2003, 100: 5413–5418
Stenger-Smith JD. Intrinsically electrically conducting polymers. Synthesis, characterization, and their applications. Prog Polym Sci, 1998, 23: 57–79
Schmidt CE, Shastri VR, Vacanti JP, Langer R. Stimulation of neurite outgrowth using an electrically conducting polymer. Proc Natl Acad Sci USA, 1997, 94: 8948–8953
Wong JY, Langer R, Ingber DE. Electrical conducting polymers can nonnvasively control the shape and growth of mammalian-cells. Proc Natl Acad Sci USA, 1994, 91: 3201–3204
Guimard NK, Gomez N, Schmidt CE. Conducting polymers in biomedical engineering. Prog Polym Sci, 2007, 32: 876–921
Shi GX, Rouabhia M, Wang ZX, Dao LH, Zhang Z. A novel electrically conductive and biodegradable composite made of polypyrrole nanoparticles and polylactide. Biomaterials, 2004, 25: 2477–2488
Richardson RT, Wise AK, Thompson BC, Flynn BO, Atkinson PJ, Fretwell NJ, Fallon JB, Wallace GG, Shepherd RK, Clark GM, O’Leary SJ. Polypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons. Biomaterials, 2009, 30: 2614–2624
Xu H, Holzwarth JM, Yan Y, Xu P, Zheng H, Yin Y, Li S, Ma PX. Conductive PPY/PDLLA conduit for peripheral nerve regeneration. Biomaterials, 2014, 35: 225–235
Jeong SI, Jun ID, Choi MJ, Nho YC, Lee YM, Shin H. Development of electroactive and elastic nanofibers that contain polyaniline and poly(l-lactide-co-epsilon-caprolactone) for the control of cell adhesion. Macromol Biosci, 2008, 8: 627–637
Wei ZX, Faul CFJ. Aniline oligomers-Architecture, function and new opportunities for nanostructured materials. Macromol Rapid Commun, 2008, 29: 280–292
Zhang XY, Qi HX, Wang SQ, Feng L, Ji Y, Tao L, Li SX, Wei Y. Cellular responses of aniline oligomers: a preliminary study. Toxicol Res, 2012, 1: 201–205
Huang LH, Zhuang XL, Hu J, Lang L, Zhang PB, Wang Y, Chen XS, Wei Y, Jing XB. Synthesis of biodegradable and electroactive multiblock polylactide and aniline pentamer copolymer for tissue engineering applications. Biomacromolecules, 2008, 9: 850–858
Stridsberg KM, Ryner M, Albertsson AC. Controlled ring-opening polymerization: polymers with designed macromolecular architecture. Adv Polym Sci, 2002, 157: 41–65
Guo BL, Finne-Wistrand A, Albertsson AC. Molecular architecture of electroactive and biodegradable copolymers composed of polylactide and carboxyl-capped aniline trimer. Biomacromolecules, 2010, 11: 855–863
Guo BL, Finne-Wistrand A, Albertsson AC. Universal two-step approach to degradable and electroactive block copolymers and networks from combined ring-opening polymerization and postfunctionalization via oxidative coupling reactions. Macromolecules, 2011, 44: 5227–5236
Guo BL, Finne-Wistrand A, Albertsson AC. Simple route to sizetunable degradable and electroactive nanoparticles from the self-assembly of conducting coil-rod-coil triblock copolymers. Chem Mater, 2011, 23: 4045–4055
Guo BL, Finne-Wistrand A, Albertsson AC. Enhanced electrical conductivity by macromolecular architecture: hyperbranched electroactive and degradable block copolymers based on poly (epsiloncaprolactone) and aniline pentamer. Macromolecules, 2010, 43: 4472–4480
Guo BL, Finne-Wistrand A, Albertsson AC. Degradable and electroactive hydrogels with tunable electrical conductivity and swelling behavior. Chem Mater, 2011, 23: 1254–1262
Guo BL, Finne-Wistrand A, Albertsson AC. Versatile functionalization of polyester hydrogels with electroactive aniline oligomers. J Polym Sci, Part A: Polym Chem, 2011, 49: 2097–2105
Guo BL, Finne-Wistrand A, Albertsson AC. Facile synthesis of degradable and electrically conductive polysaccharide hydrogels. Biomacromolecules, 2011, 12: 2601–2609
Guo BL, Finne-Wistrand A, Albertsson AC. Electroactive hydrophilic polylactide surface by covalent modification with tetraaniline. Macromolecules, 2012, 45: 652–659
Guo BL, Sun Y, Finne-Wistrand A, Mustafa K, Albertsson AC. Electroactive tubular porous scaffolds with degradability and non-cytotoxicity for neural tissue regeneration. Acta Biomater, 2012, 8: 144–153
Ercole F, Davis TP, Evans RA. Photo-responsive systems and biomaterials: photochromic polymers, light-triggered self-assembly, surface modification, fluorescence modulation and beyond. Polym Chem, 2010, 1: 37–54
Dai S, Ravi P, Tam KC. Thermo- and photo-responsive polymeric systems. Soft Matter, 2009, 5: 2513–2533
Jin CF, Yan RS, Huang JG. Cellulose substance with reversible photo-responsive wettability by surface modification. J Mater Chem, 2011, 21: 17519–17525
Blasco E, del Barrio J, Sanchez-Somolinos C, Pinol M, Oriol L. Light induced molecular release from vesicles based on amphiphilic linear-dendritic block copolymers. Polym Chem, 2013, 4: 2246–2254
Peng K, Tomatsu I, Kros A. Light controlled protein release from a supramolecular hydrogel. Chem Commun, 2010, 46: 4094–4096
Altunbas A, Pochan DJ. Peptide-based and polypeptide-based hydrogels for drug delivery and tissue engineering. Top Curr Chem, 2012, 310: 135–167
Deming TJ. Synthetic polypeptides for biomedical applications. Prog Polym Sci, 2007, 32: 858–875
Li LQ, Charati MB, Kiick KL. Elastomeric polypeptide-based biomaterials. Polym Chem, 2010, 1: 1160–1170
Kopecěk J, Rejmanová P. Enzymatically degradable bonds in synthetic polymers. In: Bruck SD. Ed. Controlled Drug Delivery, Vol. I. Boca Raton, FL: CRC Press, 1983, 81
Brandl FP, Seitz AK, Tessmar JKV, Blunk T, Gopferich AM. Enzymatically degradable poly(ethylene glycol) based hydrogels for adipose tissue engineering. Biomaterials, 2010, 31: 3957–3966
West JL, Hubbell JA. Polymeric biomaterials with degradation sites for proteases involved in cell migration. Macromolecules, 1999, 32: 241–244
Jun I, Park KM, Lee DY, Park KD, Shin H. Control of adhesion, focal adhesion assembly, and differentiation of myoblasts by enzymatically crosslinked cell-interactive hydrogels. Macromol Res, 2011, 19: 911–920
Barnes CP, Sell SA, Boland ED, Simpson DG, Bowlin GL. Nanofiber technology: designing the next generation of tissue engineering scaffolds. Adv Drug Delivery Rev, 2007, 59: 1413–1433
Wei GB, Ma PX. Partially nanofibrous architecture of 3D tissue engineering scaffolds. Biomaterials, 2009, 30: 6426–6434
Wei GB, Ma PX. Nanostructured biomaterials for regeneration. Adv Funct Mater, 2008, 18: 3568–3582
Vasita R, Katti DS. Nanofibers and their applications in tissue engineering. Int J Nanomed, 2006, 1: 15–30
Wei GB, Ma PX. Macroporous and nanofibrous polymer scaffolds and polymer/bone-like apatite composite scaffolds generated by sugar spheres. J Biomed Mater Res A, 2006, 78A: 306–315
Ma PX, Zhang RY. Synthetic nano-scale fibrous extracellular matrix. J Biomed Mater Res, 1999, 46: 60–72
Chen VJ, Ma PX. Nano-fibrous poly(l-lactic acid) scaffolds with interconnected spherical macropores. Biomaterials, 2004, 25: 2065–2073
Liu XH, Ma PX. Phase separation, pore structure, and properties of nanofibrous gelatin scaffolds. Biomaterials, 2009, 30: 4094–4103
Liu XH, Jin XB, Ma PX. Nanofibrous hollow microspheres self-assembled from star-shaped polymers as injectable cell carriers for knee repair. Nat Mater, 2011, 10: 398–406
Kang SW, Yang HS, Seo SW, Han DK, Kim BS. Apatite-coated poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for bone tissue engineering. J Biomed Mater Res A, 2008, 85A: 747–756
Lee TJ, Kang SW, Bhang SH, Kang JM, Kim BS. Apatite-coated porous poly(lactic-co-glycolic acid) microspheres as an injectable bone substitute. J Biomater Sci, Polym Ed, 2010, 21: 635–645
Holzwarth JM, Ma PX. Biomimetic nanofibrous scaffolds for bone tissue engineering. Biomaterials, 2011, 32: 9622–9629
Zhang R, Ma PX. Poly(alpha-hydroxyl acids)/hydroxyapatite porous composites for bone tissue engineering. I. Preparation and morphology. J Biomed Mater Res, 1999, 44: 446–455
Boccaccini AR, Blaker JJ. Bioactive composite materials for tissue engineering scaffolds. Expert Rev Med Devices, 2005, 2: 303–317
Dorozhkin SV. Nanosized and nanocrystalline calcium orthophosphates. Acta Biomater, 2010, 6: 715–734
Chou YF, Dunn JCY, Wu BM. In vitro response of MC3T3-E1 preosteoblasts within three-dimensional apatite-coated PLGA scaffolds. J Biomed Mater Res B, 2005, 75B: 81–90
Zhang RY, Ma PX. Porous poly(l-lactic acid)/apatite composites created by biomimetic process. J Biomed Mater Res, 1999, 45: 285–293
Liao S, Watari F, Zhu Y, Uo M, Akasaka T, Wang W, Xu G, Gui F. The degradation of the three layered nano-carbonated hydroxyapatite/collagen/PLGA composite membrane in vitro. Dent Mater, 2007, 23: 1120–1128
Ngiam M, Liao SS, Patil AJ, Cheng ZY, Chan CK, Ramakrishna S. The fabrication of nano-hydroxyapatite on PLGA and PLGA/collagen nanofibrous composite scaffolds and their effects in osteoblastic behavior for bone tissue engineering. Bone, 2009, 45: 4–16
Wei GB, Ma PX. Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering. Biomaterials, 2004, 25: 4749–4757
Lei B, Shin KH, Noh DY, Jo IH, Koh YH, Choi WY, Kim HE. Nanofibrous gelatin-silica hybrid scaffolds mimicking the native extracellular matrix (ECM) using thermally induced phase separation. J Mater Chem, 2012, 22: 14133–14140
Liu X, Smith LA, Hu J, Ma PX. Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering. Biomaterials, 2009, 30: 2252–2258
He CL, Xiao GY, Jin XB, Sun CH, Ma PX. Electrodeposition on nanofibrous polymer scaffolds: rapid mineralization, tunable calcium phosphate composition and topography. Adv Funct Mater, 2010, 20: 3568–3576
He C, Jin X, Ma PX. Calcium phosphate deposition rate, structure and osteoconductivity on electrospun poly(l-lactic acid) matrix using electrodeposition or simulated body fluid incubation. Acta Biomater, 2014, 10: 419–427
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Guo, B., Ma, P.X. Synthetic biodegradable functional polymers for tissue engineering: a brief review. Sci. China Chem. 57, 490–500 (2014). https://doi.org/10.1007/s11426-014-5086-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11426-014-5086-y