- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China. Corresponding author: XIANG Zhou, E-mail: xiangzhou15@hotmail.com;
Objective To review the research progress of the seed cells, scaffolds, growth factors, and the prospects for clinical application of the intervertebral disc regeneration. Methods The recent literature concerning the regeneration strategies and tissue engineering for treatment of degenerative intervertebral disc disease was extensively reviewed and summarized. Results Seed cells based on mesenchymal stem cells (MSCs) and multiple-designed biomimetic scaffolds are the hot topic in the field of intervertebral disc regeneration. It needs to be further investigated how to effectively combine the interactions of seed cells, scaffolds, and growth factors and to play their regulation function. Conclusion The biological regeneration of intervertebral disc would have a very broad prospects for clinical application in future.
Citation: FU Weili,XIANG Zhou.. REGENERATION STRATEGIES OF INTERVERTEBRAL DISC. Chinese Journal of Reparative and Reconstructive Surgery, 2013, 27(2): 227-232. doi: 10.7507/1002-1892.20130049 Copy
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46. | 31 Miyazaki T, Kobayashi S, Takeno K, et al. A phenotypic comparison of proteoglycan production of intervertebral disc cells isolated from rats, rabbits, and bovine tails; which animal model is most suitable to study tissue engineering and biological repair of human disc disorders? Tissue Eng Part A, 2009, 15(12): 3835-3846. 32 Joshi A, Fussell G, Thomas J, et al. Functional compressive mechanics of a PVA/PVP nucleus pulposus replacement. Biomaterials, 2006, 27(2): 176-184. 33 Vernengo J, Fussell GW, Smith NG, et al. Evaluation of novel injectable hydrogels for nucleus pulposus replacement. J Biomed Mater Res B Appl Biomater, 2008, 84(1): 64-69. |
47. | 34 Reza AT, Nicoll SB. Characterization of novel photocrosslinked carboxymethylcellulose hydrogels for encapsulation of nucleus pulposus cells. Acta Biomater, 2010, 6(1): 179-186. 35 Collin EC, Grad S, Zeugolis DI, et al. An injectable vehicle for nucleus pulposus cell-based therapy. Biomaterials, 2011, 32(11): 2862-2870. 36 Stern S, Lindenhayn K, Schultz O, et al. Cultivation of porcine cells from the nucleus pulposus in a fibrin/hyaluronic acid matrix. Acta Orthop Scand, 2000, 71(5): 496-502. |
48. | 37 Richardson SM, Hughes N, Hunt JA, et al. Human mesenchymal stem cell differentiation to NP-like cells in chitosan-glycerophosphate hydrogels. Biomaterials, 2008, 29(1): 85-93. 38 Halloran DO, Grad S, Stoddart M, et al. An injectable cross-linked scaffold for nucleus pulposus regeneration. Biomaterials, 2008, 29(4): 438-447. |
49. | 39 Huang B, Zhuang Y, Li CQ, et al. Regeneration of the intervertebral disc with nucleus pulposus cell-seeded collagen II/hyaluronan/chondroitin-6-sulfate tri-copolymer constructs in a rabbit disc degeneration model. Spine (Phila Pa 1976), 2011, 36(26): 2252-2259. 40 Park SH, Gil ES, Cho H, et al. Intervertebral disk tissue engineering using biphasic silk composite scaffolds. Tissue Eng Part A, 2012, 18(5-6): 447-458. 41 Park SH, Cho H, Gil ES, et al. Silk-fibrin/hyaluronic acid composite gels for nucleus pulposus tissue regeneration. Tissue Eng Part A, 2011, 17(23-24): 2999-3009. |
50. | 42 Ko YK, Kim SH, Ha HJ, et al. Hybrid type of tissue-engineered biodisc using annulus fibrosus seeded PLGA scaffold and nucleus pulposus seeded MPEG-PCL hydrogel: Preliminary Study. Key Eng Mater, 2007, 342-343: 173-176. 43 Bowles RD, Williams RM, Zipfel WR, et al. Self-assembly of aligned tissue-engineered annulus fibrosus and intervertebral disc composite via collagen gel contraction. Tissue Eng Part A, 2010, 16(4): 1339-1348. 44 Nesti LJ, Li WJ, Shanti RM, et al. Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam. Tissue Eng Part A, 2008, 14(9): 1527-1537. 45 Moss IL, Gordon L, Woodhouse KA, et al. A novel thiol-modified hyaluronan and elastin-like polypetide composite material for tissue engineering of the nucleus pulposus of the intervertebral disc. Spine (Phila Pa 1976), 2011, 36(13): 1022-1029. |
51. | 46 Wan Y, Feng G, Shen FH, et al. Biphasic scaffold for annulus fibrosus tissue regeneration. Biomaterials, 2008, 29(6): 643-652. 47 Nerurkar NL, Sen S, Huang AH, et al. Engineered disc-like angle-ply structures for intervertebral disc replacement. Spine (Phila Pa 1976), 2010, 35(8): 867-873. 48 An HS, Masuda K, Inoue N. Intervertebral disc degeneration: biological and biomechanical factors. J Orthop Sci, 2006, 11(5): 541-552. 49 Specchia N, Pagnotta A, Toesca A, et al. Cytokines and growth factors in the protruded intervertebral disc of the lumbar spine. Eur Spine J, 2002, 11(2): 145-151. |
52. | 50 Okuda S, Myoui A, Ariga K, et al. Mechanisms of age-related decline in insulin-like growth factor-I dependent proteoglycan synthesis in rat intervertebral disc cells. Spine (Phila Pa 1976), 2001, 26(22): 2421-2426. 51 Wei A, Brisby H, Chung SA, et al. Bone morphogenetic protein-7 protects human intervertebral disc cells in vitro from apoptosis. Spine J, 2008, 8(3): 466-474. 52 Gilbertson L, Ahn SH, Teng PN, et al. The effects of recombinant human bone morphogenetic protein-2, recombinant human bone morphogenetic protein-12, and adenoviral bone morphogenetic protein-12 on matrix synthesis in human annulus fibrosis and nucleus pulposus cells. Spine J, 2008, 8(3): 449-456. 53 Kim JS, Ellman MB, An HS, et al. Insulin-like growth factor 1 synergizes with bone morphogenetic protein 7-mediated anabolism in bovine intervertebral disc cells. Arthritis Rheum, 2010, 62(12): 3706-3715. 54 Moon SH, Nishida K, Gilbertson LG, et al. Biologic response of human intervertebral disc cells to gene therapy cocktail. Spine (Phila Pa 1976), 2008, 33(17): 1850-1855. 55 Liu Y, Li JM, Hu YG. Transplantation of gene-modified nucleus pulposus cells reverses rabbit intervertebral disc degeneration. Chin Med J (Engl), 2011, 124(16): 2431-2437. 56 Fassett DR, Kurd MF, Vaccaro AR. Biologic solutions for degenerative disk disease. J Spinal Disord Tech, 2009, 22(4): 297-308. 57 Yoon ST, Park JS, Kim KS, et al. ISSLS prize winner: LMP-1 upregulates intervertebral disc cell production of proteoglycans and BMPs in vitro and in vivo. Spine (Phila Pa 1976), 2004, 29(23): 2603-2611. 58 Pratsinis H, Kletsas D. Growth factors in intervertebral disc homeostasis. Connect Tissue Res, 2008, 49(3): 273-276. 59 Risbud MV, Di Martino A, Guttapalli A, et al. Toward an optimum system for intervertebral disc organ culture: TGF-beta 3 enhances nucleus pulposus and anulus fibrosus survival and function through modulation of TGF-beta-R expression and ERK signaling. Spine (Phila Pa 1976), 2006, 31(8): 884-890. 60 Lotz JC. Animal models of intervertebral disc degeneration: lessons learned. Spine (Phila Pa 1976), 2004, 29(23): 2742-2750. |
53. | |
54. | Wallach CJ, Gilbertson LG, Kang JD. Gene therapy applications for intervertebral disc degeneration. Spine (Phila Pa 1976), 2003, 28(15 Suppl): S93-98. |
55. | Putzier M, Schneider SV, Funk JF, et al. The surgical treatment of the lumbar disc prolapse: nucleotomy with additional transpedicular dynamic stabilization versus nucleotomy alone. Spine (Phila Pa 1976), 2005, 30(5): E109-114. |
56. | Shim CS, Lee SH, Shin HD, et al. CHARITE versus ProDisc: a comparative study of a minimum 3-year follow-up. Spine (Phila Pa 1976), 2007, 32(9): 1012-1018. |
57. | Delamarter R, Zigler JE, Balderston RA, et al. Prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of the ProDisc-L total disc replacement compared with circumferential arthrodesis for the treatment of two-level lumbar degenerative disc disease: results at twenty-four months. J Bone Joint Surg (Am), 2011, 93(8): 705-715. |
58. | Zigler J, Delamarter R, Spivak JM, et al. Results of the prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of the ProDisc-L total disc replacement versus circumferential fusion for the treatment of 1-level degenerative disc disease. Spine (Phila Pa 1976), 2007, 32(11): 1155-1163. |
59. | Kandel R, Roberts S, Urban JP. Tissue engineering and the intervertebral disc: the challenges. Eur Spine J, 2008, 17 Suppl 4: 480-491. |
60. | Kalson NS, Richardson S, Hoyland JA. Strategies for regeneration of the intervertebral disc. Regen Med, 2008, 3(5): 717-729. |
61. | Meisel HJ, Siodla V, Ganey T, et al. Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc. Biomol Eng, 2007, 24(1): 5-21. |
62. | Richardson SM, Hoyland JA, Mobasheri R, et al. Mesenchymal stem cells in regenerative medicine: opportunities and challenges for articular cartilage and intervertebral disc tissue engineering. J Cell Physiol, 2010, 222(1): 23-32. |
63. | Hoogendoorn RJ, Lu ZF, Kroeze RJ, et al. Adipose stem cells for intervertebral disc regeneration: current status and concepts for the future. J Cell Mol Med, 2008, 12(6A): 2205-2216. |
64. | Leung VY, Chan D, Cheung KM. Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction. Eur Spine J, 2006, 15 Suppl 3: S406-413. |
65. | Sobajima S, Vadala G, Shimer A, et al. Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J, 2008, 8(6): 888-896. |
66. | Le Maitre CL, Baird P, Freemont AJ, et al. An in vitro study investigating the survival and phenotype of mesenchymal stem cells following injection into nucleus pulposus tissue. Arthritis Res Ther, 2009, 11(1): R20. |
67. | Bron JL, Vonk LA, Smit TH, et al. Engineering alginate for intervertebral disc repair. J Mech Behav Biomed Mater, 2011, 4(7): 1196-1205. |
68. | Roughley P, Hoemann C, Desrosiers E, et al. The potential of chitosan-based gels containing intervertebral disc cells for nucleus pulposus supplementation. Biomaterials, 2006, 27(3): 388-396. |
69. | Pereira DR, Silva-Correia J, Caridade SG, et al. Development of gellan gum-based microparticles/hydrogel matrices for application in the intervertebral disc regeneration. Tissue Eng Part C Methods, 2011, 17(10): 961-972. |
70. | Nagae M, Ikeda T, Mikami Y, et al. Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. Tissue Eng, 2007, 13(1): 147-158. |
71. | Le Visage C, Yang SH, Kadakia L, et al. Small intestinal submucosa as a potential bioscaffold for intervertebral disc regeneration. Spine (Phila Pa 1976), 2006, 31(21): 2423-2431. |
72. | O’Halloran DM, Pandit AS. Tissue-engineering approach to regenerating the intervertebral disc. Tissue Eng, 2007, 13(8): 1927-1954. |
73. | Pfeiffer M, Boudriot U, Pfeiffer D, et al. Intradiscal application of hyaluronic acid in the non-human primate lumbar spine: radiological results. Eur Spine J, 2003, 12(1): 76-83. |
74. | Mercuri JJ, Gill SS, Simionescu DT. Novel tissue-derived biomimetic scaffold for regenerating the human nucleus pulposus. J Biomed Mater Res A, 2011, 96(2): 422-435. |
75. | Sakai D, Mochida J, Iwashina T, et al. Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials, 2006, 27(3): 335-345. |
76. | Leone G, Torricelli P, Chiumiento A, et al. Amidic alginate hydrogel for nucleus pulposus replacement. J Biomed Mater Res A, 2008, 84(2): 391-401. |
77. | Dang JM, Sun DD, Shin-Ya Y, et al. Temperature-responsive hydroxybutyl chitosan for the culture of mesenchymal stem cells and intervertebral disk cells. Biomaterials, 2006, 27(3): 406-418. |
78. | Mauth C, Bono E, Haas S, et al. Cell-seeded polyurethane-fibrin structures—a possible system for intervertebral disc regeneration. Eur Cell Mater, 2009, 18: 27-39. |
79. | Gruber HE, Hoelscher G, Ingram JA, et al. Culture of human anulus fibrosus cells on polyamide nanofibers: extracellular matrix production. Spine (Phila Pa 1976), 2009, 34(1): 4-9. |
80. | Razaq S, Wilkins RJ, Urban JP. The effect of extracellular pH on matrix turnover by cells of the bovine nucleus pulposus. Eur Spine J, 2003, 12(4): 341-349. |
81. | Nerurkar NL, Elliott DM, Mauck RL. Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering. J Orthop Res, 2007, 25(8): 1018-1028. |
82. | Wan Y, Feng G, Shen FH, et al. Novel biodegradable poly (1, 8-octanediol malate) for annulus fibrosus regeneration. Macromol Biosci, 2007, 7(11): 1217-1224. |
83. | Whatley BR, Kuo J, Shuai C, et al. Fabrication of a biomimetic elastic intervertebral disk scaffold using additive manufacturing. Biofabrication, 2011, 3(1): 015004. |
84. | Hiyama A, Mochida J, Iwashina T, et al. Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res, 2008, 26(5): 589-600. |
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- 46. 31 Miyazaki T, Kobayashi S, Takeno K, et al. A phenotypic comparison of proteoglycan production of intervertebral disc cells isolated from rats, rabbits, and bovine tails; which animal model is most suitable to study tissue engineering and biological repair of human disc disorders? Tissue Eng Part A, 2009, 15(12): 3835-3846. 32 Joshi A, Fussell G, Thomas J, et al. Functional compressive mechanics of a PVA/PVP nucleus pulposus replacement. Biomaterials, 2006, 27(2): 176-184. 33 Vernengo J, Fussell GW, Smith NG, et al. Evaluation of novel injectable hydrogels for nucleus pulposus replacement. J Biomed Mater Res B Appl Biomater, 2008, 84(1): 64-69.
- 47. 34 Reza AT, Nicoll SB. Characterization of novel photocrosslinked carboxymethylcellulose hydrogels for encapsulation of nucleus pulposus cells. Acta Biomater, 2010, 6(1): 179-186. 35 Collin EC, Grad S, Zeugolis DI, et al. An injectable vehicle for nucleus pulposus cell-based therapy. Biomaterials, 2011, 32(11): 2862-2870. 36 Stern S, Lindenhayn K, Schultz O, et al. Cultivation of porcine cells from the nucleus pulposus in a fibrin/hyaluronic acid matrix. Acta Orthop Scand, 2000, 71(5): 496-502.
- 48. 37 Richardson SM, Hughes N, Hunt JA, et al. Human mesenchymal stem cell differentiation to NP-like cells in chitosan-glycerophosphate hydrogels. Biomaterials, 2008, 29(1): 85-93. 38 Halloran DO, Grad S, Stoddart M, et al. An injectable cross-linked scaffold for nucleus pulposus regeneration. Biomaterials, 2008, 29(4): 438-447.
- 49. 39 Huang B, Zhuang Y, Li CQ, et al. Regeneration of the intervertebral disc with nucleus pulposus cell-seeded collagen II/hyaluronan/chondroitin-6-sulfate tri-copolymer constructs in a rabbit disc degeneration model. Spine (Phila Pa 1976), 2011, 36(26): 2252-2259. 40 Park SH, Gil ES, Cho H, et al. Intervertebral disk tissue engineering using biphasic silk composite scaffolds. Tissue Eng Part A, 2012, 18(5-6): 447-458. 41 Park SH, Cho H, Gil ES, et al. Silk-fibrin/hyaluronic acid composite gels for nucleus pulposus tissue regeneration. Tissue Eng Part A, 2011, 17(23-24): 2999-3009.
- 50. 42 Ko YK, Kim SH, Ha HJ, et al. Hybrid type of tissue-engineered biodisc using annulus fibrosus seeded PLGA scaffold and nucleus pulposus seeded MPEG-PCL hydrogel: Preliminary Study. Key Eng Mater, 2007, 342-343: 173-176. 43 Bowles RD, Williams RM, Zipfel WR, et al. Self-assembly of aligned tissue-engineered annulus fibrosus and intervertebral disc composite via collagen gel contraction. Tissue Eng Part A, 2010, 16(4): 1339-1348. 44 Nesti LJ, Li WJ, Shanti RM, et al. Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam. Tissue Eng Part A, 2008, 14(9): 1527-1537. 45 Moss IL, Gordon L, Woodhouse KA, et al. A novel thiol-modified hyaluronan and elastin-like polypetide composite material for tissue engineering of the nucleus pulposus of the intervertebral disc. Spine (Phila Pa 1976), 2011, 36(13): 1022-1029.
- 51. 46 Wan Y, Feng G, Shen FH, et al. Biphasic scaffold for annulus fibrosus tissue regeneration. Biomaterials, 2008, 29(6): 643-652. 47 Nerurkar NL, Sen S, Huang AH, et al. Engineered disc-like angle-ply structures for intervertebral disc replacement. Spine (Phila Pa 1976), 2010, 35(8): 867-873. 48 An HS, Masuda K, Inoue N. Intervertebral disc degeneration: biological and biomechanical factors. J Orthop Sci, 2006, 11(5): 541-552. 49 Specchia N, Pagnotta A, Toesca A, et al. Cytokines and growth factors in the protruded intervertebral disc of the lumbar spine. Eur Spine J, 2002, 11(2): 145-151.
- 52. 50 Okuda S, Myoui A, Ariga K, et al. Mechanisms of age-related decline in insulin-like growth factor-I dependent proteoglycan synthesis in rat intervertebral disc cells. Spine (Phila Pa 1976), 2001, 26(22): 2421-2426. 51 Wei A, Brisby H, Chung SA, et al. Bone morphogenetic protein-7 protects human intervertebral disc cells in vitro from apoptosis. Spine J, 2008, 8(3): 466-474. 52 Gilbertson L, Ahn SH, Teng PN, et al. The effects of recombinant human bone morphogenetic protein-2, recombinant human bone morphogenetic protein-12, and adenoviral bone morphogenetic protein-12 on matrix synthesis in human annulus fibrosis and nucleus pulposus cells. Spine J, 2008, 8(3): 449-456. 53 Kim JS, Ellman MB, An HS, et al. Insulin-like growth factor 1 synergizes with bone morphogenetic protein 7-mediated anabolism in bovine intervertebral disc cells. Arthritis Rheum, 2010, 62(12): 3706-3715. 54 Moon SH, Nishida K, Gilbertson LG, et al. Biologic response of human intervertebral disc cells to gene therapy cocktail. Spine (Phila Pa 1976), 2008, 33(17): 1850-1855. 55 Liu Y, Li JM, Hu YG. Transplantation of gene-modified nucleus pulposus cells reverses rabbit intervertebral disc degeneration. Chin Med J (Engl), 2011, 124(16): 2431-2437. 56 Fassett DR, Kurd MF, Vaccaro AR. Biologic solutions for degenerative disk disease. J Spinal Disord Tech, 2009, 22(4): 297-308. 57 Yoon ST, Park JS, Kim KS, et al. ISSLS prize winner: LMP-1 upregulates intervertebral disc cell production of proteoglycans and BMPs in vitro and in vivo. Spine (Phila Pa 1976), 2004, 29(23): 2603-2611. 58 Pratsinis H, Kletsas D. Growth factors in intervertebral disc homeostasis. Connect Tissue Res, 2008, 49(3): 273-276. 59 Risbud MV, Di Martino A, Guttapalli A, et al. Toward an optimum system for intervertebral disc organ culture: TGF-beta 3 enhances nucleus pulposus and anulus fibrosus survival and function through modulation of TGF-beta-R expression and ERK signaling. Spine (Phila Pa 1976), 2006, 31(8): 884-890. 60 Lotz JC. Animal models of intervertebral disc degeneration: lessons learned. Spine (Phila Pa 1976), 2004, 29(23): 2742-2750.
- 53.
- 54. Wallach CJ, Gilbertson LG, Kang JD. Gene therapy applications for intervertebral disc degeneration. Spine (Phila Pa 1976), 2003, 28(15 Suppl): S93-98.
- 55. Putzier M, Schneider SV, Funk JF, et al. The surgical treatment of the lumbar disc prolapse: nucleotomy with additional transpedicular dynamic stabilization versus nucleotomy alone. Spine (Phila Pa 1976), 2005, 30(5): E109-114.
- 56. Shim CS, Lee SH, Shin HD, et al. CHARITE versus ProDisc: a comparative study of a minimum 3-year follow-up. Spine (Phila Pa 1976), 2007, 32(9): 1012-1018.
- 57. Delamarter R, Zigler JE, Balderston RA, et al. Prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of the ProDisc-L total disc replacement compared with circumferential arthrodesis for the treatment of two-level lumbar degenerative disc disease: results at twenty-four months. J Bone Joint Surg (Am), 2011, 93(8): 705-715.
- 58. Zigler J, Delamarter R, Spivak JM, et al. Results of the prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of the ProDisc-L total disc replacement versus circumferential fusion for the treatment of 1-level degenerative disc disease. Spine (Phila Pa 1976), 2007, 32(11): 1155-1163.
- 59. Kandel R, Roberts S, Urban JP. Tissue engineering and the intervertebral disc: the challenges. Eur Spine J, 2008, 17 Suppl 4: 480-491.
- 60. Kalson NS, Richardson S, Hoyland JA. Strategies for regeneration of the intervertebral disc. Regen Med, 2008, 3(5): 717-729.
- 61. Meisel HJ, Siodla V, Ganey T, et al. Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc. Biomol Eng, 2007, 24(1): 5-21.
- 62. Richardson SM, Hoyland JA, Mobasheri R, et al. Mesenchymal stem cells in regenerative medicine: opportunities and challenges for articular cartilage and intervertebral disc tissue engineering. J Cell Physiol, 2010, 222(1): 23-32.
- 63. Hoogendoorn RJ, Lu ZF, Kroeze RJ, et al. Adipose stem cells for intervertebral disc regeneration: current status and concepts for the future. J Cell Mol Med, 2008, 12(6A): 2205-2216.
- 64. Leung VY, Chan D, Cheung KM. Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction. Eur Spine J, 2006, 15 Suppl 3: S406-413.
- 65. Sobajima S, Vadala G, Shimer A, et al. Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J, 2008, 8(6): 888-896.
- 66. Le Maitre CL, Baird P, Freemont AJ, et al. An in vitro study investigating the survival and phenotype of mesenchymal stem cells following injection into nucleus pulposus tissue. Arthritis Res Ther, 2009, 11(1): R20.
- 67. Bron JL, Vonk LA, Smit TH, et al. Engineering alginate for intervertebral disc repair. J Mech Behav Biomed Mater, 2011, 4(7): 1196-1205.
- 68. Roughley P, Hoemann C, Desrosiers E, et al. The potential of chitosan-based gels containing intervertebral disc cells for nucleus pulposus supplementation. Biomaterials, 2006, 27(3): 388-396.
- 69. Pereira DR, Silva-Correia J, Caridade SG, et al. Development of gellan gum-based microparticles/hydrogel matrices for application in the intervertebral disc regeneration. Tissue Eng Part C Methods, 2011, 17(10): 961-972.
- 70. Nagae M, Ikeda T, Mikami Y, et al. Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. Tissue Eng, 2007, 13(1): 147-158.
- 71. Le Visage C, Yang SH, Kadakia L, et al. Small intestinal submucosa as a potential bioscaffold for intervertebral disc regeneration. Spine (Phila Pa 1976), 2006, 31(21): 2423-2431.
- 72. O’Halloran DM, Pandit AS. Tissue-engineering approach to regenerating the intervertebral disc. Tissue Eng, 2007, 13(8): 1927-1954.
- 73. Pfeiffer M, Boudriot U, Pfeiffer D, et al. Intradiscal application of hyaluronic acid in the non-human primate lumbar spine: radiological results. Eur Spine J, 2003, 12(1): 76-83.
- 74. Mercuri JJ, Gill SS, Simionescu DT. Novel tissue-derived biomimetic scaffold for regenerating the human nucleus pulposus. J Biomed Mater Res A, 2011, 96(2): 422-435.
- 75. Sakai D, Mochida J, Iwashina T, et al. Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials, 2006, 27(3): 335-345.
- 76. Leone G, Torricelli P, Chiumiento A, et al. Amidic alginate hydrogel for nucleus pulposus replacement. J Biomed Mater Res A, 2008, 84(2): 391-401.
- 77. Dang JM, Sun DD, Shin-Ya Y, et al. Temperature-responsive hydroxybutyl chitosan for the culture of mesenchymal stem cells and intervertebral disk cells. Biomaterials, 2006, 27(3): 406-418.
- 78. Mauth C, Bono E, Haas S, et al. Cell-seeded polyurethane-fibrin structures—a possible system for intervertebral disc regeneration. Eur Cell Mater, 2009, 18: 27-39.
- 79. Gruber HE, Hoelscher G, Ingram JA, et al. Culture of human anulus fibrosus cells on polyamide nanofibers: extracellular matrix production. Spine (Phila Pa 1976), 2009, 34(1): 4-9.
- 80. Razaq S, Wilkins RJ, Urban JP. The effect of extracellular pH on matrix turnover by cells of the bovine nucleus pulposus. Eur Spine J, 2003, 12(4): 341-349.
- 81. Nerurkar NL, Elliott DM, Mauck RL. Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering. J Orthop Res, 2007, 25(8): 1018-1028.
- 82. Wan Y, Feng G, Shen FH, et al. Novel biodegradable poly (1, 8-octanediol malate) for annulus fibrosus regeneration. Macromol Biosci, 2007, 7(11): 1217-1224.
- 83. Whatley BR, Kuo J, Shuai C, et al. Fabrication of a biomimetic elastic intervertebral disk scaffold using additive manufacturing. Biofabrication, 2011, 3(1): 015004.
- 84. Hiyama A, Mochida J, Iwashina T, et al. Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res, 2008, 26(5): 589-600.