Prospects of Bioactive Chitosan-Based Scaffolds in Tissue Engineering and Regenerative Medicine

  • M. PrabaharanEmail author
  • P. R. Sivashankari
Part of the Springer Series on Polymer and Composite Materials book series (SSPCM)


Chitosan, a natural-based polymer obtained by alkaline deacetylation of chitin, is non-toxic, biocompatible, and biodegradable. Due to its desired properties, chitosan-based materials are widely considered to fabricate scaffolds for tissue engineering and regenerative medicine. These scaffolds provide characteristic advantages, such as preservation of cellular phenotype, binding and enhancement of bioactive factors, control of gene expression, and synthesis and deposition of tissue-specific extracellular matrix (ECM), to tissue regeneration. Therefore, the scaffolds based on chitosan and its composites have potential to be used in bone, cartilage, liver, nerve, and musculoskeletal tissue engineering.


Chitosan Scaffolds Tissue engineering Bioactivity Regenerative medicine 



The authors thank DST-Nano Mission, Department of Science and Technology, Government of India for their financial support.


  1. 1.
    Prabaharan M, Rodriguez-Perez MA, de Saja JA, Mano JF (2007) Preparation and characterization of poly(L-lactic acid)-chitosan hybrid scaffolds with drug release capability. J Biomed Mater Res B Appl Biomater 81:427–434CrossRefGoogle Scholar
  2. 2.
    Han DK, Park KD, Hubbell JA, Kim YH (1998) Surface characteristics and biocompatibility of lactide-based poly (ethylene glycol) scaffolds for tissue engineering. J Biomater Sci Polym Ed 9:667–680CrossRefGoogle Scholar
  3. 3.
    Olad A, Azhar FF (2014) The synergetic effect of bioactive ceramic and nanoclay on the properties of chitosan–gelatin/nanohydroxyapatite–montmorillonite scaffold for bone tissue engineering. Ceram Int 40:10061–10072CrossRefGoogle Scholar
  4. 4.
    Suh FJK, Matthew HWT (2000) Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials 21:2589–2598CrossRefGoogle Scholar
  5. 5.
    Mano JF, Hungerford G, Ribelles JLG (2008) Bioactive poly (L-lactic acid)-chitosan hybrid scaffolds. Mater Sci Eng, C 28:1356–1365CrossRefGoogle Scholar
  6. 6.
    Santo VE, Duarte ARC, Gomes ME, Mano JF, Reis RL (2010) Hybrid 3D structure of poly(D, L-lactic acid) loaded with chitosan/chondroitin sulfate nanoparticles to be used as carriers for biomacromolecules in tissue engineering. J Supercrit Fluids 54:320–327CrossRefGoogle Scholar
  7. 7.
    Martel-Estrada SA, Martínez-Pérez CA, Chacón-Nava JG, García-Casillas PE, Olivas-Armendáriz I (2011) In vitro bioactivity of chitosan/poly (D, L-lactide-co-glycolide) composites. Mater Lett 65:137–141CrossRefGoogle Scholar
  8. 8.
    Niu X, Feng Q, Wang M, Guo X, Zheng C (2009) In vitro degradation and release behavior of porous poly(lactic acid) scaffolds containing chitosan microspheres as a carrier for BMP-2-derived synthetic peptide. Polym Degrad Stab 94:176–182CrossRefGoogle Scholar
  9. 9.
    Santo VE, Duarte ARC, Popa EG, Gomes ME, Mano JF, Reis RL (2012) Enhancement of osteogenic differentiation of human adipose derived stem cells by the controlled release of platelet lysates from hybrid scaffolds produced by supercritical fluid foaming. J Control Release 162:19–27CrossRefGoogle Scholar
  10. 10.
    Xiaoyan A, Jun Y, Min W, Haiyue Z, Li C, Kangdec Y, Fanglian Y (2008) Preparation of chitosan–gelatin scaffold containing tetrandrine-loaded nano-aggregates and its controlled release behavior. Int J Pharm 350:257–264CrossRefGoogle Scholar
  11. 11.
    Zhao L, Burguera EF, Xu HHK, Amin N, Ryou H, Arola DD (2010) Fatigue and human umbilical cord stem cell seeding characteristics of calcium phosphate–chitosan–biodegradable fiber scaffolds. Biomaterials 31:840–847CrossRefGoogle Scholar
  12. 12.
    Wen Z, Zhang L, Chen C, Liu Y, Wu C, Dai C (2013) A construction of novel iron-foam-based calcium phosphate/chitosan coating biodegradable scaffold material. Mater Sci Eng, C 33:1022–1031CrossRefGoogle Scholar
  13. 13.
    Meng D, Dong L, Wen Y, Xie Q (2015) Effects of adding resorbable chitosan microspheres to calcium phosphate cements for bone regeneration. Mater Sci Eng, C 47:266–272CrossRefGoogle Scholar
  14. 14.
    Rezwan K, Chen QZ, Blaker JJ, Boccaccini AB (2006) Biodegradable and bioactive porous polymer, inorganic composite scaffold for bone tissue engineering. Biomaterials 27:3413–3431CrossRefGoogle Scholar
  15. 15.
    Mansur HS, Costa HS (2008) Nanostructured poly (vinyl alcohol)/bioactive glass and poly (vinyl alcohol)/chitosan/bioactive glass hybrid scaffolds for biomedical applications. Chem Eng J 137:72–83CrossRefGoogle Scholar
  16. 16.
    Couto DS, Hong Z, Mano JF (2009) Development of bioactive and biodegradable chitosan-based injectable systems containing bioactive glass nanoparticles. Acta Biomater 5:115–123CrossRefGoogle Scholar
  17. 17.
    Peter M, Binulal NS, Soumya S, Nair SV, Furuike T, Tamura H, Jayakumar R (2010) Nanocomposite scaffolds of bioactive glass ceramic nanoparticles disseminated chitosan matrix for tissue engineering applications. Carbohydr Polym 79:284–289CrossRefGoogle Scholar
  18. 18.
    Peter M, Binulal NS, Nair SV, Selvamurugan N, Tamurac H, Jayakumar R (2010) Novel biodegradable chitosan–gelatin/nano-bioactive glass ceramic composite scaffolds for alveolar bone tissue engineering. Chem Eng J 158:353–361CrossRefGoogle Scholar
  19. 19.
    Yang G, Yang X, Zhang L, Lin M, Sun X, Chen X, Gou Z (2012) Counterionic biopolymers-reinforced bioactive glass scaffolds with improved mechanical properties in wet state. Mater Lett 75:80–83CrossRefGoogle Scholar
  20. 20.
    Nazemi K, Azadpour P, Moztarzadeh F, Urbanska AM, Mozafari M, Tissue-engineered chitosan/bioactive glass bone scaffolds integrated with PLGA nanoparticles: a therapeutic design for on-demand drug delivery. Mater Lett 138:16–20Google Scholar
  21. 21.
    Yao Q, Nooeaid P, Roether JA, Dong Y, Zhang Q, Boccaccini AR (2013) Bioglass®-based scaffolds incorporating polycaprolactone and chitosan coatings for controlled vancomycin delivery. Ceram Int 39:7517–7522CrossRefGoogle Scholar
  22. 22.
    Soundrapandian C, Mahato A, Kundu B, Datta S, Sa B, Basu D (2014) Development and effect of different bioactive silicate glass scaffolds: In vitro evaluation for use as a bone drug delivery system. J Mech Behav Biomed Mater 40:1–12CrossRefGoogle Scholar
  23. 23.
    Pon-On W, Charoenphandhu N, Teerapornpuntakit J, Thongbunchoo J, Krishnamra N, Tang IM (2014) Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: a bone tissue engineering applications. Mater Sci Eng, C 38:63–72CrossRefGoogle Scholar
  24. 24.
    Nazemi K, Azadpour P, Moztarzadeh f, Urbanska AM, Mozafari M (2015) Tissue-engineered chitosan/bioactive glass bone scaffolds integrated with PLGA nanoparticles: A therapeutic design for on-demand drug delivery. Mater Lett 138:16–20CrossRefGoogle Scholar
  25. 25.
    Oliveira JM, Sousa RA, Kotobuki N, Tadokoro M, Hirose M, Mano JF, Reis RL, Ohgushi H (2009) The osteogenic differentiation of rat bone marrow stromal cells cultured with dexamethasone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles. Biomaterials 30:804–813CrossRefGoogle Scholar
  26. 26.
    Zhu W, Wang M, Fu Y, Castro NJ, Fu SW, Zhang LG (2015) Engineering a biomimetic three-dimensional nanostructured bone model for breast cancer bone metastasis study. Acta Biomater 14:164–174CrossRefGoogle Scholar
  27. 27.
    Iwasaki N, Yamane ST, Majima T, Kasahara Y, Minami A, Harada K, Nonaka S, Maekawa N, Tamura H, Tokura S, Shiono M, Monde K, Nishimura S (2004) Feasibility of polysaccharide hybrid materials for scaffolds in cartilage tissue engineering: evaluation of chondrocyte adhesion to polyion complex fibers prepared from alginate and chitosan. Biomacromolecules 5:828–833CrossRefGoogle Scholar
  28. 28.
    Liverani L, Roether JA, Nooeaid P, Trombetta M, Schubert DW, Boccaccini AR (2012) Simple fabrication technique for multilayered stratified composite scaffolds suitable for interface tissue engineering. Mater Sci Eng, A 557:54–58CrossRefGoogle Scholar
  29. 29.
    Choi B, Kim S, Lin B, Wu BM, Lee M (2014) Cartilaginous extracellular matrix-modified chitosan hydrogels for cartilage tissue engineering. ACS Appl Mate Interfaces 6(22):20110–20121CrossRefGoogle Scholar
  30. 30.
    Kim SE, Park JH, Cho YW, Chung H, Jeong SY, Lee EB, Kwon IC (2003) Porous chitosan scaffold containing microspheres loaded with transforming growth factor-β1: implications for cartilage tissue engineering. J Control Release 91:365–374CrossRefGoogle Scholar
  31. 31.
    Bi L, Li D, Liu J, Hu Y, Yang P, Yang B, Yuan Z (2011) Fabrication and characterization of a biphasic scaffold for osteochondral tissue engineering. Mater Lett 65:2079–2082CrossRefGoogle Scholar
  32. 32.
    Silva JM, Georgi N, Costa R, Sher P, Reis RL, van Blitterswijk CA, Karperien M, Mano JF (2013) Nanostructured 3D constructs based on chitosan and chondroitin sulphate multilayers for cartilage tissue engineering. PLoS ONE 8(2):e55451CrossRefGoogle Scholar
  33. 33.
    Yan S, Zhang K, Liu Z, Zhang X, Gan L, Cao B, Chen X, Cui L, Yin J (2013) Fabrication of poly(L-glutamic acid)/chitosan polyelectrolyte complex porous scaffolds fortissue engineering. J Mater Chem B 1(11):1541–1551CrossRefGoogle Scholar
  34. 34.
    Lee SY, Wee AS, Lim CK, Abbas AA, Selvaratnam L, Merican AM, Ahmad TS, Kamarul T (2013) Supermacroporous poly(vinyl alcohol)-carboxylmethyl chitosan-poly(ethylene glycol) scaffold: An in vitro and in vivo pre-assessments for cartilage tissue engineering. J Mater Sci Mater Med 24(6):1561–1570CrossRefGoogle Scholar
  35. 35.
    Chen ZX, Li MC, Xin MH, Chen XD, Mao YF (2015) Preparation and characterization of histidine-grafted-chitosan/ poly(L-lactide) scaffolds. J Funct Mater 46(5):05118–05122Google Scholar
  36. 36.
    Kamoun EA (2015) N-succinyl chitosan-dialdehyde starch hybrid hydrogels for biomedical applications. J Adv Res doi: 10.1016/j.jare.2015.02.002
  37. 37.
    Wang XH, Li DP, Wang WJ, Feng QL, Cui FZ, Xu YX, Song XH, van der Werf M (2003) Crosslinked collagen/chitosan matrix for artificial livers. Biomaterials 24:3213–3220CrossRefGoogle Scholar
  38. 38.
    Wang X, Yan Y, Lin F, Xiong Z, Wu R, Zhang R, Lu Q (2005) Preparation and characterization of a collagen/chitosan/heparin matrix for an implantable bioartificial liver. J Biomater Sci Polym Ed 16:1063–1080CrossRefGoogle Scholar
  39. 39.
    Yang J, Cung TW, Nagaoka M, Goto M, Cho CS, Akaike T (2001) Hepatocyte-specific porous polymer-scaffolds of alginate/galactosylated chitosan sponge for liver-tissue engineering. Biotechnol Lett 23:1385–1389CrossRefGoogle Scholar
  40. 40.
    Chen F, Tian M, Zhang D, Wang J, Wang Q, Yu X, Zhang X, Wan C (2012) Preparation and characterization of oxidized alginate covalently cross-linked galactosylated chitosan scaffold for liver tissue engineering. Mater Sci Eng, C 32:310–320CrossRefGoogle Scholar
  41. 41.
    Lee KH, Shin SJ, Kim CB, Kim JK, Cho YW, Chung BG, Lee SH (2010) Microfluidic synthesis of pure chitosan microfibers for bio-artificial liver chip. Lab Chip 10:1328–1334CrossRefGoogle Scholar
  42. 42.
    Fan J, Shang Y, Yang J, Yuan Y (2009) Preparation of galactosylated hyaluronic acid/chitosan scaffold for liver tissue engineering. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 26:1271–1275Google Scholar
  43. 43.
    Yang ZY, Mo LH, Duan HM, Li XG (2010) Effects of chitosan/collagen substrates on the behavior of rat neural stem cells. Sci China Life Sciences 53(2):215–222CrossRefGoogle Scholar
  44. 44.
    Huang J, Hu X, Lu L, Ye Z, Zhang Q, Luo Z (2010) Electrical regulation of Schwann cells using conductive polypyrrole/chitosan polymers. J Biomed Mater Res A 93(1):164–174Google Scholar
  45. 45.
    Wrobel S, Serra SC, Ribeiro-Samy S, Sousa N, Heimann C, Barwig C, Grothe C, Salgado AJ, Haastert-Talini K (2014) In vitro evaluation of cell-seeded chitosan films for peripheral nerve tissue engineering. Tissue Eng Part A 20:2339–2349CrossRefGoogle Scholar
  46. 46.
    Morelli S, Piscioneri A, Messina A, Salerno S, Al-Fageeh MB, Drioli E, Bartolo LD (2015) Neuronal growth and differentiation on biodegradable membranes. J Tissue Eng Regen Med 9(2):106–117CrossRefGoogle Scholar
  47. 47.
    Freier T, Montenegro R, Shan Koh H, Shoichet MS (2005) Chitin-based tubes for tissue engineering in the nervous system. Biomaterials 26:4624–4632CrossRefGoogle Scholar
  48. 48.
    Valmikinathan CM, Mukhatyar VJ, Jain A, Karumbaiah L, Dasari M, Bellamkonda RV (2012) Photocrosslinkable chitosan based hydrogels for neural tissue engineering. Soft Matter 8:1964–1976CrossRefGoogle Scholar
  49. 49.
    Masuko T, Iwasaki N, Yamane S, Funakoshi T, Majima T, Minami A, Ohsuga N, Ohta T, Nishimura SI (2005) Chitosan–RGDSGGC conjugate as a scaffold material for musculoskeletal tissue engineering. Biomaterials 26:5339–5347CrossRefGoogle Scholar
  50. 50.
    Rinki K, Dutta PK (2010) Physicochemical and biological activity study of genipin-crosslinked chitosan scaffolds prepared by using supercritical carbon dioxide for tissue engineering applications. Int J Biol Macromol 46:261–266CrossRefGoogle Scholar
  51. 51.
    Zhang L, Li Y, Li L, Guo B, Ma PX (2014) Non-cytotoxic conductive carboxymethyl-chitosan/aniline pentamer Hydrogels. React Funct Polym 82:81–88CrossRefGoogle Scholar
  52. 52.
    Cheung HK, Han TTY, Marecak DM, Watkins JF, Amsden BG, Flynn LE (2014) Composite hydrogel scaffolds incorporating decellularized adipose tissue for soft tissue engineering with adipose-derived stem cells. Biomaterials 35:1914–1923CrossRefGoogle Scholar
  53. 53.
    Martel-Estrada SA, Olivas-Armendáriz I, Santos-Rodríguez E, Martínez-Pérez CA, García-Casillas PE, Hernández-Paz J, Rodríguez-González CA, Chapa-González C (2014) Evaluation of in vitro bioactivity of chitosan/mimosa tenuiflora composites. Mater Lett 119:146–149CrossRefGoogle Scholar

Copyright information

© Springer India 2016

Authors and Affiliations

  1. 1.Department of ChemistryHindustan Institute of Technology and ScienceChennaiIndia

Personalised recommendations