研究生: |
楊書睿 Yang, Shu-Rui |
---|---|
論文名稱: |
複合性材料於軟骨組織工程之應用 The application of biphasic materials on cartilage tissue engineering |
指導教授: | 朱一民 |
口試委員: |
陳志平
鄭明輝 劉繼賢 駱俊良 |
學位類別: |
博士 Doctor |
系所名稱: |
工學院 - 化學工程學系 Department of Chemical Engineering |
論文出版年: | 2013 |
畢業學年度: | 101 |
論文頁數: | 103 |
中文關鍵詞: | 軟骨組織工程 、膠原蛋白二型 、複合性材料 、氫氧磷灰石 、軟骨素 、間葉幹細胞 |
相關次數: | 點閱:2 下載:0 |
分享至: |
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
對於大區域關節軟骨疾病,現今雖已經有很多治療方法,包括藥物治療、細胞治療及關節置換,但仍有其限制存。本研究希望研發關節組織支架,包括可促進軟骨、軟骨下骨及硬骨之再生,然後置入病患患部達到較完整及可靠的治療方式。本研究以天然高分子膠原蛋白I、II 型與雙相三鈣磷酸鹽當作支架各分區細胞間質構成成分,並以骨髓、羊水及臍帶血幹細胞植入,並利用相同無血清培養,以評估軟骨化能力,除此之外,軟骨素A在關節再生與修復的角色與機制也會被研究跟探討,並評估是否有誘導間葉幹細胞至軟骨細胞的潛力。
利用膠原蛋白I型凝膠結合膠原蛋白II型支架與氫氧磷灰石支架作為模仿關節組織的細胞間質分布的複合型支架。其間葉幹細胞在此複合型支架的軟骨特徵表現,都相對於單一膠原蛋白二型支架上表現較佳,骨髓間葉幹細胞則被發現在此複合型支架上比羊水與臍帶血間葉幹細胞較容易趨向軟骨,在動物實驗上,複合型支架修軟關節缺損的能力相對單一膠原蛋白二型支架好。
分子量2250的軟骨素A可大幅抑制軟骨細胞團塊的金屬蛋白基質分解酵素基因,且無抑制其膠原蛋白二型與醣多蛋白基因其表現,而導致膠原蛋白二型蛋白分泌比無添加的組別多,以利保護軟骨,但此機制並沒有刺激軟骨細胞表現過多軟骨特徵基因,而且與實驗團隊相關研究比較結果,軟骨素A並不適宜作為誘導間葉幹細胞至軟骨細胞。
本研究證明了此天然複合型支架適合修復關節缺損的醫療器材,而骨髓間葉幹細胞於此複合型支架上具有相對優秀的軟骨化潛力,軟骨素A的保護軟骨機制被驗證,但不具有誘導間葉幹細胞之潛力。
1. National Science Foundation Workshop on Tissue Engineering. Lake Tahoe, CA. 1988.
2. NEREM RM, SAMBANIS A. Tissue Engineering: From Biology to Biological Substitutes. Tissue Engineering 1995;1(1):3-13.
3. Buckwalter J. Articular cartilage: tissue design and chondrocyte}matrix interactions. AAOS Inst Course Lect 1998;47:477-486.
4. Temenoff JS, Mikos AG. Review: tissue engineering for regeneration of articular cartilage. Biomaterials 2000;21(5):431-440.
5. Cordoba F, Nimni ME. Chondroitin sulfate and other sulfate containing chondroprotective agents may exhibit their effects by overcoming a deficiency of sulfur amino acids. Osteoarthritis Cartilage 2003;11(3):228-230.
6. Lippiello L. Glucosamine and chondroitin sulfate: biological response modifiers of chondrocytes under simulated conditions of joint stress. Osteoarthritis Cartilage 2003;11(5):335-342.
7. Palmieri L, Conte A, Giovannini L, Lualdi P, Ronca G. Metabolic fate of exogenous chondroitin sulfate in the experimental animal. Arzneimittelforschung 1990;40(3):319-323.
8. Conte A, Volpi N, Palmieri L, Bahous I, Ronca G. Biochemical and pharmacokinetic aspects of oral treatment with chondroitin sulfate. Arzneimittelforschung 1995;45(8):918-925.
9. Wang W, Zhang M, Lu W, Zhang X, Ma D, Rong X, Yu C, Jin Y. Cross-linked collagen-chondroitin sulfate-hyaluronic acid imitating extracellular matrix as scaffold for dermal tissue engineering. Tissue engineering. Part C, Methods 2010;16(2):269-279.
10. Chen WC, Wei YH, Chu IM, Yao CL. Effect of chondroitin sulphate C on the in vitro and in vivo chondrogenesis of mesenchymal stem cells in crosslinked type II collagen scaffolds. J Tissue Eng Regen Med 2012.
11. Asik M, Ciftci F, Sen C, Erdil M, Atalar A. The microfracture technique for the treatment of full-thickness articular cartilage lesions of the knee: midterm results. Arthroscopy: the journal of arthroscopic & related surgery: official publication of the Arthroscopy Association of North America and the International Arthroscopy Association 2008;24(11):1214-1220.
12. Steadman JR, Rodkey WG, Singleton SB, Briggs KK. Microfracture technique forfull-thickness chondral defects: Technique and clinical results. Operative Techniques in Orthopaedics 1997;7(4):300-304 =.
13. Steadman JR, Rodkey WG, Briggs KK, Rodrigo JJ. The microfracture technique to treat full thickness articular cartilage defects of the knee. Der Orthopäde 1999;28(1):26-32.
14. Johnson LL. Arthroscopic abrasion arthroplasty: a review. Clinical orthopaedics and related research 2001(391 Suppl):S306-317.
15. Cross A. A fresh osteochondral allograft alternative. journal of arthroplasty 2002;17:50-53.
16. H W. Operative Behandlung der Osteochondrosis dissecans des Kniegelenkes. Z Orthop 1964;98:333-356.
17. Horas U, Pelinkovic D, Herr G, Aigner T, Schnettler R. Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. A prospective, comparative trial. J Bone Joint Surg Am 2003;85-A(2):185-192.
18. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994;331(14):889-895.
19. Bentley G, Minas T. Treating joint damage in young people. BMJ 2000;320(7249):1585-1588.
20. Martin I, Miot S, Barbero A, Jakob M, Wendt D. Osteochondral tissue engineering. Journal of biomechanics 2007;40(4):750-765.
21. Wendt D, Jakob M, Martin I. Bioreactor-based engineering of osteochondral grafts: from model systems to tissue manufacturing. Journal of bioscience and bioengineering 2005;100(5):489-494.
22. Martin I, Wendt D, Heberer M. The role of bioreactors in tissue engineering. Trends in biotechnology 2004;22(2):80-86.
23. Siclari A, Mascaro G, Gentili C, Cancedda R, Boux E. A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year. Clinical orthopaedics and related research 2012;470(3):910-919.
24. Grimmer JF, Gunnlaugsson CB, Alsberg E, Murphy HS, Kong HJ, Mooney DJ, Weatherly RA. Tracheal reconstruction using tissue-engineered cartilage. Archives of otolaryngology--head & neck surgery 2004;130(10):1191-1196.
25. Dhandayuthapani B, Yoshida Y, Maekawa T, Kumar DS. Polymeric Scaffolds in Tissue Engineering Application: A Review. International Journal of Polymer Science 2011;2011
26. Ren T, Ren J, Jia X, Pan K. The bone formation in vitro and mandibular defect repair using PLGA porous scaffolds. J Biomed Mater Res A 2005;74(4):562-569.
27. Woodfield TBF, Van Blitterswijk CA, De Wijn J, Sims TJ, Hollander AP, Riesle J. Polymer scaffolds fabricated with pore-size gradients as a model for studying the zonal organization within tissue-engineered cartilage constructs. Tissue engineering 2005;11(9-10):1297-1311.
28. Gray ML, Pizzanelli AM, Grodzinsky AJ, Lee RC. Mechanical and physiochemical determinants of the chondrocyte biosynthetic response. Journal of orthopaedic research: official publication of the Orthopaedic Research Society 1988;6(6):777-792.
29. Guilak F. Biomechanical factors in osteoarthritis. Best practice & research. Clinical rheumatology 2011;25(6):815-823.
30. Cao Y, Rodriguez A, Vacanti M, Ibarra C, Arevalo C, Vacanti CA. Comparative study of the use of poly(glycolic acid), calcium alginate and pluronics in the engineering of autologous porcine cartilage. Journal of biomaterials science. Polymer edition 1998;9(5):475-487.
31. Ko CS, Huang JP, Huang CW, Chu IM. Type II collagen-chondroitin sulfate-hyaluronan scaffold cross-linked by genipin for cartilage tissue engineering. J Biosci Bioeng 2009;107(2):177-182.
32. Chen WC, Yao CL, Wei YH, Chu IM. Evaluating osteochondral defect repair potential of autologous rabbit bone marrow cells on type II collagen scaffold. Cytotechnology 2011;63(1):13-23.
33. Chang KY, Hung LH, Chu IM, Ko CS, Lee YD. The application of type II collagen and chondroitin sulfate grafted PCL porous scaffold in cartilage tissue engineering. J Biomed Mater Res A 2010;92(2):712-723.
34. Haisch A, Loch A, David J, Pruss A, Hansen R, Sittinger M. Preparation of a pure autologous biodegradable fibrin matrix for tissue engineering. Medical & biological engineering & computing 2000;38(6):686-689.
35. Knudson CB, Knudson W. Hyaluronan and CD44: modulators of chondrocyte metabolism. Clinical orthopaedics and related research 2004(427 Suppl):S152-162.
36. Knudson W, Casey B, Nishida Y, Eger W, Kuettner KE, Knudson CB. Hyaluronan oligosaccharides perturb cartilage matrix homeostasis and induce chondrocytic chondrolysis. Arthritis and rheumatism 2000;43(5):1165-1174.
37. Hu X, Li D, Gao C. Chemically cross-linked chitosan hydrogel loaded with gelatin for chondrocyte encapsulation. Biotechnology journal 2011;6(11):1388-1396.
38. Ragetly GR, Slavik GJ, Cunningham BT, Schaeffer DJ, Griffon DJ. Cartilage tissue engineering on fibrous chitosan scaffolds produced by a replica molding technique. Journal of biomedical materials research. Part A 2010;93(1):46-55.
39. Griffon DJ, Sedighi MR, Schaeffer DV, Eurell JA, Johnson AL. Chitosan scaffolds: interconnective pore size and cartilage engineering. Acta biomaterialia 2006;2(3):313-320.
40. Guo Y, Yuan T, Xiao Z, Tang P, Xiao Y, Fan Y, Zhang X. Hydrogels of collagen/chondroitin sulfate/hyaluronan interpenetrating polymer network for cartilage tissue engineering. Journal of materials science. Materials in medicine 2012;23(9):2267-2279.
41. Chou C-H, Lee H-S, Siow TY, Lin M-H, Kumar A, Chang Y-C, Chang C, Huang G-S. Temporal MRI characterization of gelatin/hyaluronic acid/chondroitin sulfate sponge for cartilage tissue engineering. Journal of biomedical materials research. Part A 2012.
42. Migneault I, Dartiguenave C, Bertrand MJ, Waldron KC. Glutaraldehyde: behavior in aqueous solution, reaction with proteins, and application to enzyme crosslinking. Biotechniques 2004;37(5):790-796, 798-802.
43. Avila MY, Navia JL. Effect of genipin collagen crosslinking on porcine corneas. J Cataract Refract Surg 2010;36(4):659-664.
44. Bigi A, Cojazzi G, Panzavolta S, Roveri N, Rubini K. Stabilization of gelatin films by crosslinking with genipin. Biomaterials 2002;23(24):4827-4832.
45. Chang Y, Tsai CC, Liang HC, Sung HW. In vivo evaluation of cellular and acellular bovine pericardia fixed with a naturally occurring crosslinking agent (genipin). Biomaterials 2002;23(12):2447-2457.
46. Chang Y, Tsai CC, Liang HC, Sung HW. Reconstruction of the right ventricular outflow tract with a bovine jugular vein graft fixed with a naturally occurring crosslinking agent (genipin) in a canine model. J Thorac Cardiovasc Surg 2001;122(6):1208-1218.
47. Sung HW, Liang IL, Chen CN, Huang RN, Liang HF. Stability of a biological tissue fixed with a naturally occurring crosslinking agent (genipin). J Biomed Mater Res 2001;55(4):538-546.
48. Tsai CC, Chang Y, Sung HW, Hsu JC, Chen CN. Effects of heparin immobilization on the surface characteristics of a biological tissue fixed with a naturally occurring crosslinking agent (genipin): an in vitro study. Biomaterials 2001;22(6):523-533.
49. Tsai CC, Huang RN, Sung HW, Liang HC. In vitro evaluation of the genotoxicity of a naturally occurring crosslinking agent (genipin) for biologic tissue fixation. J Biomed Mater Res 2000;52(1):58-65.
50. El-Ghannam A. Bone reconstruction: from bioceramics to tissue engineering. Expert review of medical devices 2005;2(1):87-101.
51. Włodarski KH, Włodarski PK, Galus R. Bioactive composites for bone regeneration. Review. Ortopedia, traumatologia, rehabilitacja 2008;10(3):201-210.
52. Rao RR, Roopa HN, Kannan TS. Solid state synthesis and thermal stability of HAP and HAP – β-TCP composite ceramic powders. Journal of Materials Science: Materials in Medicine 1997;8(8):511-518
53. Krajewski A, Ravaglioli A, di Sanseverino LR, Marchetti F, Monticelli G. The behaviour of apatite-based ceramics in relation to the critical 1150°–1250°C temperature range. Biomaterials 1984;5(2):105-108
54. Kurashina K, Kurita H, Wu Q, Ohtsuka A, Kobayashi H. Ectopic osteogenesis with biphasic ceramics of hydroxyapatite and tricalcium phosphate in rabbits. Biomaterials 2002;23(2):407-412.
55. Eggli PS, Müller W, Schenk RK. Porous hydroxyapatite and tricalcium phosphate cylinders with two different pore size ranges implanted in the cancellous bone of rabbits. A comparative histomorphometric and histologic study of bony ingrowth and implant substitution. Clinical orthopaedics and related research 1988(232):127-138.
56. Daculsi G. Biphasic calcium phosphate concept applied to artificial bone, implant coating and injectable bone substitute. Biomaterials 1998;19(16):1473-1478.
57. Darney PD, Monroe SE, Klaisle CM, Alvarado A. Clinical evaluation of the Capronor contraceptive implant: preliminary report. Am J Obstet Gynecol 1989;160(5 Pt 2):1292-1295.
58. Combes C, Rey C. Adsorption of proteins and calcium phosphate materials bioactivity. Biomaterials 2002;23(13):2817-2823.
59. LeGeros RZ. Calcium phosphates in oral biology and medicine. Monogr Oral Sci 1991;15:1-201.
60. Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Experimental cell research 1998;238(1):265-272.
61. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284(5411):143-7.
62. Lee JW, Kim YH, Kim S-H, Han SH, Hahn SB. Chondrogenic differentiation of mesenchymal stem cells and its clinical applications. Yonsei medical journal 2004;45 Suppl:41-47.
63. Heino TJ, Hentunen TA, Vaananen HK. Conditioned medium from osteocytes stimulates the proliferation of bone marrow mesenchymal stem cells and their differentiation into osteoblasts. Exp Cell Res 2004;294(2):458-68.
64. Palumbo SL, Li W-J. Osteoprotegerin Enhances Osteogenesis of Human Mesenchymal Stem Cells. Tissue engineering. Part A 2013.
65. Birmingham E, Niebur GL, McHugh PE, Shaw G, Barry FP, McNamara LM. Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. European cells & materials 2012;23:13-27.
66. de Peppo GM, Sjovall P, Lenneras M, Strehl R, Hyllner J, Thomsen P, Karlsson C. Osteogenic potential of human mesenchymal stem cells and human embryonic stem cell-derived mesodermal progenitors: a tissue engineering perspective. Tissue Eng Part A 2010;16(11):3413-3426.
67. Bochev I, Elmadjian G, Kyurkchiev D, Tzvetanov L, Altankova I, Tivchev P, Kyurkchiev S. Mesenchymal stem cells from human bone marrow or adipose tissue differently modulate mitogen-stimulated B-cell immunoglobulin production in vitro. Cell Biol Int 2008;32(4):384-393.
68. Ochi M, Uchio Y, Tobita M, Kuriwaka M. Current Concepts in Tissue Engineering Technique for Repair of Cartilage Defect. Artificial Organs 2001;25(3):172–179.
69. Crawford DC, DeBerardino TM, Williams RJ, 3rd. NeoCart, an autologous cartilage tissue implant, compared with microfracture for treatment of distal femoral cartilage lesions: an FDA phase-II prospective, randomized clinical trial after two years. The Journal of bone and joint surgery. American volume 2012;94(11):979-989.
70. Crawford DC, Heveran CM, Cannon WD, Jr., Foo LF, Potter HG. An autologous cartilage tissue implant NeoCart for treatment of grade III chondral injury to the distal femur: prospective clinical safety trial at 2 years. The American journal of sports medicine 2009;37(7):1334-1343.
71. 廖俊仁. 生物技術:一次修復關節軟骨. 科學人 2009:4.
72. Chiang H, Liao CJ, Hsieh CH, Shen CY, Huang YY, Jiang CC. Clinical feasibility of a novel biphasic osteochondral composite for matrix-associated autologous chondrocyte implantation. Osteoarthritis Cartilage 2013;21(4):589-598.
73. Pieper JS, van der Kraan PM, Hafmans T, Kamp J, Buma P, van Susante JL, van den Berg WB, Veerkamp JH, van Kuppevelt TH. Crosslinked type II collagen matrices: preparation, characterization, and potential for cartilage engineering. Biomaterials 2002;23(15):3183-92.
74. Mathews S, Mathew SA, Gupta PK, Bhonde R, Totey S. Glycosaminoglycans enhance osteoblast differentiation of bone marrow derived human mesenchymal stem cells. Journal of Tissue Engineering and Regenerative Medicine 2012.
75. Frescaline G, Bouderlique T, Huynh MB, Papy-Garcia D, Courty J, Albanese P. Glycosaminoglycans mimetics potentiate the clonogenicity, proliferation, migration and differentiation properties of rat mesenchymal stem cells. Stem Cell Research 2012;8(2):180-192.
76. Sirko S, von Holst A, Wizenmann A, Gotz M, Faissner A. Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells. Development 2007;134(15):2727-2738.
77. Varghese S, Hwang NS, Canver AC, Theprungsirikul P, Lin DW, Elisseeff J. Chondroitin sulfate based niches for chondrogenic differentiation of mesenchymal stem cells. Matrix Biol 2008;27(1):12-21.
78. Kinneberg KR, Nirmalanandhan VS, Juncosa-Melvin N, Powell HM, Boyce ST, Shearn JT, Butler DL. Chondroitin-6-sulfate incorporation and mechanical stimulation increase MSC-collagen sponge construct stiffness. J Orthop Res 2010;28(8):1092-1099.
79. Chen WC, Yao CL, Chu IM, Wei YH. Compare the effects of chondrogenesis by culture of human mesenchymal stem cells with various type of the chondroitin sulfate C. J Biosci Bioeng 2011;111(2):226-231.
80. Chen WC, Wei YH, Huang JP, Chu IM, Yao CL. Biological effects of oligosaccharide chondroitin sulfate C on human articular chondrocytes. biomed Eng Appl Basic Comm 2011;23:245-253.
81. Chen H, Chevrier A, Hoemann CD, Sun J, Lascau-Coman V, Buschmann MD. Bone marrow stimulation induces greater chondrogenesis in trochlear vs condylar cartilage defects in skeletally mature rabbits. Osteoarthritis Cartilage 2013.
82. Bekkers JE, Creemers LB, Tsuchida AI, van Rijen MH, Custers RJ, Dhert WJ, Saris DB. One-stage focal cartilage defect treatment with bone marrow mononuclear cells and chondrocytes leads to better macroscopic cartilage regeneration compared to microfracture in goats. Osteoarthritis Cartilage 2013.
83. Skowronski J, Skowronski R, Rutka M. Large cartilage lesions of the knee treated with bone marrow concentrate and collagen membrane--results. Ortop Traumatol Rehabil 2013;15(1):69-76.
84. Zhu S, Zhang T, Sun C, Yu A, Qi B, Cheng H. Bone marrow mesenchymal stem cells combined with calcium alginate gel modified by hTGF-beta1 for the construction of tissue-engineered cartilage in three-dimensional conditions. Exp Ther Med 2013;5(1):95-101.
85. Sabatino MA, Santoro R, Gueven S, Jaquiery C, Wendt DJ, Martin I, Moretti M, Barbero A. Cartilage graft engineering by co-culturing primary human articular chondrocytes with human bone marrow stromal cells. J Tissue Eng Regen Med 2012.
86. Lubis AM, Lubis VK. Adult bone marrow stem cells in cartilage therapy. Acta Med Indones 2012;44(1):62-68.
87. Yang Q, Peng J, Lu SB, Xia Q, Hu YC, Xu BS, Guo QY, Wang AY, Zhao B, Zhang L and others. In vitro cartilage tissue engineering with cartilage extracellular matrix-derived porous scaffolds and bone marrow mesenchymal stem cells. Zhonghua Yi Xue Za Zhi 2011;91(17):1161-1166.
88. Bottai D, Cigognini D, Nicora E, Moro M, Grimoldi MG, Adami R, Abrignani S, Marconi AM, Di Giulio AM, Gorio A. Third trimester amniotic fluid cells with the capacity to develop neural phenotypes and with heterogeneity among sub-populations. Restor Neurol Neurosci 2012;30(1):55-68.
89. Kavakli K, Gurkok S, Caylak H, Genc O, Gamsizkan M, Yucel O, Karasahin E, Gozubuyuk A, Tasci C. Effects of human amniotic fluid on costal cartilage regeneration (an experimental study). Thorac Cardiovasc Surg 2011;59(8):484-489.
90. Ozgenel GY, Filiz G, Ozcan M. Effects of human amniotic fluid on cartilage regeneration from free perichondrial grafts in rabbits. Br J Plast Surg 2004;57(5):423-428.
91. Ozgenel GY. The influence of human amniotic fluid on the potential of rabbit ear perichondrial flaps to form cartilage tissue. Br J Plast Surg 2002;55(3):246-250.
92. Rodrigues MT, Lee SJ, Gomes ME, Reis RL, Atala A, Yoo JJ. Bilayered constructs aimed at osteochondral strategies: the influence of medium supplements in the osteogenic and chondrogenic differentiation of amniotic fluid-derived stem cells. Acta Biomater 2012;8(7):2795-2806.
93. Park JS, Shim MS, Shim SH, Yang HN, Jeon SY, Woo DG, Lee DR, Yoon TK, Park KH. Chondrogenic potential of stem cells derived from amniotic fluid, adipose tissue, or bone marrow encapsulated in fibrin gels containing TGF-beta3. Biomaterials 2011;32(32):8139-8149.
94. Kolambkar YM, Peister A, Soker S, Atala A, Guldberg RE. Chondrogenic differentiation of amniotic fluid-derived stem cells. J Mol Histol 2007;38(5):405-413.
95. Jo CH, Yoon PW, Kim H, Kang KS, Yoon KS. Comparative evaluation of in vivo osteogenic differentiation of fetal and adult mesenchymal stem cell in rat critical-sized femoral defect model. Cell Tissue Res 2013.
96. Chen X, Zhang F, He X, Xu Y, Yang Z, Chen L, Zhou S, Yang Y, Zhou Z, Sheng W and others. Chondrogenic differentiation of umbilical cord-derived mesenchymal stem cells in type I collagen-hydrogel for cartilage engineering. Injury 2013;44(4):540-549.
97. de Mara CS, Duarte AS, Sartori-Cintra AR, Luzo AC, Saad ST, Coimbra IB. Chondrogenesis from umbilical cord blood cells stimulated with BMP-2 and BMP-6. Rheumatol Int 2013;33(1):121-128.
98. Arien-Zakay H, Lazarovici P, Nagler A. Tissue regeneration potential in human umbilical cord blood. Best Pract Res Clin Haematol 2010;23(2):291-303.
99. Mara CS, Duarte AS, Sartori A, Luzo AC, Saad ST, Coimbra IB. Regulation of chondrogenesis by transforming growth factor-beta 3 and insulin-like growth factor-1 from human mesenchymal umbilical cord blood cells. J Rheumatol 2010;37(7):1519-1526.
100. Bi L, Li D, Liu J, Hu Y, Yang P, Yang B, Yuan Z. Fabrication and characterization of a biphasic scaffold for osteochondral tissue engineering. Materials Letters 2011;65(13):2079-2082.
101. Chen G, Sato T, Tanaka J, Tateishi T. Preparation of a biphasic scaffold for osteochondral tissue engineering. Materials Science and Engineering: C 2006;26(1):118-123
102. Duan X, Zhu X, Dong X, Yang J, Huang F, Cen S, Leung F, Fan H, Xiang Z. Repair of large osteochondral defects in a beagle model with a novel type I collagen / glycosaminoglycan–porous titanium biphasic scaffold Materials Science and Engineering: C.