Skip to main content
SpringerLink
Log in

Photocrosslinked layered gelatin-chitosan hydrogel with graded compositions for osteochondral defect repair

  • Biomaterials Synthesis and Characterization
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

A layered gelatin-chitosan hydrogel with graded composition was prepared via photocrosslinking to simulate the polysaccharide/collagen composition of the natural tissue and mimic the multi-layered gradient structure of the cartilage-bone interface tissue. Firstly, gelatin and carboxymethyl chitosan were reacted with glycidyl methacrylate (GMA) to obtain methacrylated gelatin (Gtn-GMA) and carboxymethyl chitosan (CS-GMA). Then, the mixed solutions of Gtn-GMA in different methacrylation degrees with CS-GMA were prepared to form the superficial, transitional and deep layers of the hydrogel, respectively under the irradiation of ultraviolet light, while polyhedral oligomeric silsesquioxane was introduced in the deep layer to improve the mechanical properties. Results suggested that the pore sizes of the superficial, transitional and deep layers of the layered hydrogel were 115 ± 30, 94 ± 34, 51 ± 12 μm, respectively and their porosities were all higher than 80 %. The compressive strengths of them were 165 ± 54, 565 ± 50 and 993 ± 108 kPa, respectively and the strain of the gradient hydrogel decreased along the thickness direction, similar to the natural tissue. The in vitro cytotoxicity results showed that the hydrogel had good cytocompatibility and the in vivo repair results of osteochondral defect demonstrated remarkable recovery by using the gradient gelatin-chitosan hydrogel, especially when the hydrogel loading transforming growth factor-β1. Therefore, it was suggested that the prepared layered gelatin-chitosan hydrogel in this study could be potentially used to promote cartilage-bone interface tissue repair.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Nukavarapu SP, Dorcemus DL. Osteochondral tissue engineering: current strategies and challenges. Biotechnol Adv. 2013;31:706–21.

    Article  Google Scholar 

  2. Chung C, Burdick JA. Engineering cartilage tissue. Adv Drug Deliv Rev. 2008;60:243–62.

    Article  Google Scholar 

  3. Matsuda H, Kitamura N, Kurokawa T, Arakaki K, Gong JP, Kanaya F, Yasuda K. Influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double-network gel implanted at the bottom of a large osteochondral defect: short-term results. BMC Musculoskelet Disord. 2013;14:50–9.

    Article  Google Scholar 

  4. Pan Y, Shen Q, Pan C, Wang J. Compressive mechanical characteristics of multi-layered gradient hydroxyapatite reinforced poly (vinyl alcohol) gel biomaterial. J Mater Sci Technol. 2013;29:551–6.

    Article  Google Scholar 

  5. Nguyen LH, Kudva AK, Guckert NL, Linse KD, Roy K. Unique biomaterial compositions direct bone marrow stem cells into specific chondrocytic phenotypes corresponding to the various zones of articular cartilage. Biomaterials. 2011;32:1327–38.

    Article  Google Scholar 

  6. Kim IL, Mauck RL, Burdick JA. Hydrogel design for cartilage tissue engineering: a case study with hyaluronic acid. Biomaterials. 2011;32:8771–82.

    Article  Google Scholar 

  7. Hollander AP, Dickinson SC, Kafienah W. Stem cells and cartilage development: complexities of a simple tissue. Stem Cells. 2010;28:1992–6.

    Article  Google Scholar 

  8. Harley BA, Lynn AK, Wissner-Gross Z, Bonfield W, Yannas IV, Gibson LJ. Design of a multiphase osteochondral scaffold III: fabrication of layered scaffolds with continuous interfaces. J Biomed Mater Res A. 2010;92:1078–93.

    Google Scholar 

  9. Nguyen LH, Kudva AK, Saxena NS, Roy K. Engineering articular cartilage with spatially-varying matrix composition and mechanical properties from a single stem cell population using a multi-layered hydrogel. Biomaterials. 2011;32:6946–52.

    Article  Google Scholar 

  10. Hu X, Ma L, Wang C, Gao C. Gelatin hydrogel prepared by photo-initiated polymerization and loaded with TGF-beta1 for cartilage tissue engineering. Macromol Biosci. 2009;9:1194–201.

    Article  Google Scholar 

  11. Bian L, Hou C, Tous E, Rai R, Mauck RL, Burdick JA. The influence of hyaluronic acid hydrogel crosslinking density and macromolecular diffusivity on human MSC chondrogenesis and hypertrophy. Biomaterials. 2013;34:413–21.

    Article  Google Scholar 

  12. Tang Y, Sun J, Fan H, Zhang X. An improved complex gel of modified gellan gum and carboxymethyl chitosan for chondrocytes encapsulation. Carbohyd Polym. 2012;88:46–53.

    Article  Google Scholar 

  13. Klein TJ, Rizzi SC, Schrobback K, Reichert JC, Jeon JE, Crawford RW, Hutmacher DW. Long-term effects of hydrogel properties on human chondrocyte behavior. Soft Matter. 2010;6:5175–83.

    Article  Google Scholar 

  14. Galois L, Hutasse S, Cortial D, Rousseau CF, Grossin L, Ronziere MC, Herbage D, Freyria A-M. Bovine chondrocyte behaviour in three-dimensional type I collagen gel in terms of gel contraction, proliferation and gene expression. Biomaterials. 2006;27:79–90.

    Article  Google Scholar 

  15. Shin H, Olsen BD, Khademhosseini A. The mechanical properties and cytotoxicity of cell-laden double-network hydrogels based on photocrosslinkable gelatin and gellan gum biomacromolecules. Biomaterials. 2012;33:3143–52.

    Article  Google Scholar 

  16. Stammen JA, Williams S, Ku DN, Guldberg RE. Mechanical properties of a novel PVA hydrogel in shear and unconfined compression. Biomaterials. 2001;22:799–806.

    Article  Google Scholar 

  17. Wu G, Su B, Zhang W, Wang C. In vitro behaviors of hydroxyapatite reinforced polyvinyl alcohol hydrogel composite. Mater Chem Phys. 2008;107:364–9.

    Article  Google Scholar 

  18. Wang J, Sutti A, Wang X, Lin T. Fast responsive and morphologically robust thermo-responsive hydrogel nanofibres from poly(N-isopropylacrylamide) and POSS crosslinker. Soft Matter. 2011;7:4364–9.

    Article  Google Scholar 

  19. Renò F, Carniato F, Rizzi M, Marchese L, Laus M, Antonioli D. POSS/gelatin-polyglutamic acid hydrogel composites: preparation, biological and mechanical characterization. J Appl Polym Sci. 2013;129:699–706.

    Article  Google Scholar 

  20. Wu J, Ge Q, Mather PT. PEG-POSS multiblock polyurethanes: synthesis, characterization and hydrogel formation. Macromolecules. 2010;43:7637–49.

    Article  Google Scholar 

  21. Im GI, Lee JH. Repair of osteochondral defects with adipose stem cells and a dual growth factor-releasing scaffold in rabbits. J Biomed Mater Res B Appl Biomater. 2010;92:552–60.

    Google Scholar 

  22. Mohan N, Dormer NH, Caldwell KL, Key VH, Berkland CJ, Detamore MS. Continuous gradients of material composition and growth factors for effective regeneration of the osteochondral interface. Tissue Eng Part A. 2011;17:2845–55.

    Article  Google Scholar 

  23. Sridhar BV, Doyle NR, Randolph MA, Anseth KS. Covalently tethered TGF-b1 with encapsulated chondrocytes in a PEG hydrogel system enhances extracellular matrix production. J Biomed Mater Res A Appl Biomater. 2014;102:4464–72.

    Google Scholar 

  24. Han FX, Zhou F, Yang XL, Zhao J, Zhao YH, Yuan XY. A pilot study of conically graded chitosan-gelatin hydrogel/PLGA scaffold with dual-delivery of TGF-β1 and BMP-2 for regeneration of cartilage-bone interface. J Biomed Mater Res B Appl Biomater. 2014. doi:10.1002/jbm.b.33314.

    Google Scholar 

  25. Pierce BF, Tronci G, Rossle M, Neffe AT, Jung F, Lendlein A. Photocrosslinked co-networks from glycidylmethacrylated gelatin and poly(ethylene glycol) methacrylates. Macromol Biosci. 2012;12:484–93.

    Article  Google Scholar 

  26. Zhu Y, Gao C, Liu X, Shen J. Surface modification of polycaprolactone membrane via aminolysis and biomacromolecule immobilization for promoting cytocompatibility of human endothelial cells. Biomacromolecules. 2002;3:1312–9.

    Article  Google Scholar 

  27. Poon YF, Zhu YB, Shen JY, Chan-Park MB, Ng SC. Cytocompatible hydrogels based on photocrosslinkable methacrylated O-carboxymethylchitosan with tunable charge: synthesis and characterization. Adv Funct Mater. 2007;17:2139–50.

    Article  Google Scholar 

  28. Tang GW, Zhang H, Zhao YH, Li XR, Yuan XY, Wang M. Prolonged release from PLGA/HAp scaffolds containing drug-loaded PLGA/gelatin composite microspheres. J Mater Sci Mater Med. 2012;23:419–29.

    Article  Google Scholar 

  29. Zhang CQ, Gao LL, Dong LM, Liu HY. Depth-dependent normal strain of articular cartilage under sliding load by the optimized digital image correlation technique. Mater Sci Eng C. 2012;32:2390–5.

    Article  Google Scholar 

  30. Han FX, Zhang H, Zhao J, Zhao YH, Yuan XY. Diverse release behaviors of water-soluble bioactive substances from fibrous membranes prepared by emulsion and suspension electrospinning. J Biomater Sci Polym Ed. 2013;24:1244–59.

    Article  Google Scholar 

  31. Han FX, Jia XL, Dai DD, Yang XL, Zhao J, Zhao YH, Yuan XY. Performance of a multilayered small-diameter vascular scaffold dual-loaded with VEGF and PDGF. Biomaterials. 2013;34:7302–13.

    Article  Google Scholar 

  32. Zhou YL, Nie W, Zhao J, Yuan XY. Rapidly in situ forming adhesive hydrogel based on a PEG-maleimide modified polypeptide through Michael addition. J Mater Sci Mater Med. 2013;24:2277–86.

    Article  Google Scholar 

  33. Xie X, Wang Y, Zhao C, Guo S, Liu S, Jia W, Tuan RS, Zhang C. Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials. 2012;33:7008–18.

    Article  Google Scholar 

  34. Keeney M, Pandit A. The osteochondral junction and its repair via bi-phasic tissue engineering scaffolds. Tissue Eng Part B. 2009;15:55–73.

    Article  Google Scholar 

  35. Tibbitt MW, Anseth KS. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol Bioeng. 2009;103:655–63.

    Article  Google Scholar 

  36. Durmaz S, Okay O. Acrylamide/2-acrylamido-2-methylpropane sulfonic acid sodium salt-based hydrogels: synthesis and characterization. Polymer. 2000;41:3693–704.

    Article  Google Scholar 

  37. Liu Y, Chan-Park MB. Hydrogel based on interpenetrating polymer networks of dextran and gelatin for vascular tissue engineering. Biomaterials. 2009;30:196–207.

    Article  Google Scholar 

  38. Elder BD, Athanasiou KA. Hydrostatic pressure in articular cartilage tissue engineering: from chondrocytes to tissue regeneration. Tissue Eng Part B Rev. 2009;15:43–53.

    Article  Google Scholar 

  39. Nguyen QT, Hwang Y, Chen AC, Varghese S, Sah RL. Cartilage-like mechanical properties of poly (ethylene glycol)-diacrylate hydrogels. Biomaterials. 2012;33:6682–90.

    Article  Google Scholar 

  40. Schinagl RM, Gurskis D, Chen AC, Sah RL. Depth-dependent confined compression modulus of full-thickness bovine articular cartilage. J Orthopaed Res. 1997;15:499–506.

    Article  Google Scholar 

  41. Zhang L, Li K, Xiao W, Zheng L, Xiao Y, Fan H, Zhang X. Preparation of collagen-chondroitin sulfate-hyaluronic acid hybrid hydrogel scaffolds and cell compatibility in vitro. Carbohyd Polym. 2011;84:118–25.

    Article  Google Scholar 

  42. Gong JP. Why are double network hydrogels so tough? Soft Matter. 2010;6:2583–90.

    Article  Google Scholar 

  43. Burdick JA, Chung C, Jia X, Randolph MA, Langer R. Controlled degradation and mechanical behavior of photopolymerized hyaluronic acid networks. Biomacromolecules. 2005;6:386–91.

    Article  Google Scholar 

  44. Gao LL, Zhang CQ, Yang YB, Shi JP, Jia YW. Depth-dependent strain fields of articular cartilage under rolling load by the optimized digital image correlation technique. Mater Sci Eng C Mater Biol Appl. 2013;33:2317–22.

    Article  Google Scholar 

  45. Sivakumaran D, Maitland D, Oszustowicz T, Hoare T. Tuning drug release from smart microgel-hydrogel composites via cross-linking. J Colloid Interf Sci. 2013;392:422–30.

    Article  Google Scholar 

  46. Li Q, Yang D, Ma G, Xu Q, Chen X, Lu F, Nie J. Synthesis and characterization of chitosan-based hydrogels. Int J Biol Macromol. 2009;44:121–7.

    Article  Google Scholar 

  47. Gentile P, Chiono V, Carmagnola I, Hatton PV. An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering. Int J Mol Sci. 2014;15:3640–59.

    Article  Google Scholar 

  48. Pasqui D, Torricelli P, De Cagna M, Fini M, Barbucci R. Carboxymethyl cellulose-hydroxyapatite hybrid hydrogel as a composite material for bone tissue engineering applications. J Biomed Mater Res A. 2014;102:1568–79.

    Article  Google Scholar 

  49. Iwakura T, Sakata R, Reddi AH. Induction of chondrogenesis and expression of superficial zone protein in synovial explants with TGF-beta1 and BMP-7. Tissue Eng Part A. 2013;19:2638–44.

    Article  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the Natural Science Foundation of China (No. 51073117) and also by the Scientific Research Foundation of Graduate School of Tianjin University. The work of mechanical test was immensely aided by the team of Professor Chunqiu Zhang in Tianjin Key Laboratory for Control Theory & Applications in Complicated Industry Systems, School of Mechanical Engineering, Tianjin University of Technology, China.

Author information

Author notes

    Authors and Affiliations

    1. School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, 300072, People’s Republic of China

      Fengxuan Han, Xiaoling Yang, Jin Zhao, Yunhui Zhao & Xiaoyan Yuan

    Authors
    1. Fengxuan Han
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Xiaoling Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Jin Zhao
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Yunhui Zhao
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Xiaoyan Yuan
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Xiaoyan Yuan.

    Additional information

    Fengxuan Han and Xiaoling Yang contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Han, F., Yang, X., Zhao, J. et al. Photocrosslinked layered gelatin-chitosan hydrogel with graded compositions for osteochondral defect repair. J Mater Sci: Mater Med 26, 160 (2015). https://doi.org/10.1007/s10856-015-5489-0

    Download citation

    • Received:

    • Accepted:

    • Published:

    • DOI: https://doi.org/10.1007/s10856-015-5489-0

    Keywords

    Search

    Navigation