组织工程双相支架修复关节软骨及软骨下骨缺损研究进展_West China Medical Journal

Authors：

 刘明 ¹ , 余曦 ² , 黄富国 ¹ , 岑石强 ¹ ,  项舟 ¹

1. ;
2. ;

Corresponding author：

项舟, Email: xiangzhou15@hotmail.com

Keywords：

组织工程; 干细胞; 骨软骨缺损; 双相支架; 修复

DOI：

10.7507/1002-0179.20140238

Video：

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通过回顾近年来国内外采用的组织工程双相支架修复软骨及软骨下骨缺损的文献，比较不同双相支架修复软骨及软骨下骨效果差别，分析其优势及存在的主要问题，并初步探讨软骨修复的合理方式和发展趋势。研究结果表明，以双相支架作为载体材料一体化修复软骨及软骨下骨缺损，较之传统方式以及其他组织工程修复途径有着不可比拟的优越性，而复合理想的种子细胞及合适生长因子后，更能促进修复效果。由此可见，双相支架有利于修复骨软骨缺损，而构建仿生化多相支架是未来研究的趋势。

Citation： 刘明, 余曦, 黄富国, 岑石强, 项舟. 组织工程双相支架修复关节软骨及软骨下骨缺损研究进展. West China Medical Journal, 2014, 29(4): 783-787. doi: 10.7507/1002-0179.20140238 Copy

1.	Qi YY, Chen X, Jiang YZ, et al. Local delivery of autologous platelet in collagen matrix simulated in situ articular cartilage repair[J]. Cell Transplant, 2009, 18(10):1161-1169.
2.	Chen WC, Yao CL, Wei YH, et al. Evaluating osteochondral defect repair potential of autologous rabbit bone marrow cells on type Ⅱ collagen scaffold[J]. Cytotechnology, 2011, 63(1):13-23.
3.	Fritz J, Janssen P, Gaissmaier C, et al. Articular cartilage defects in the knee——basics, therapies and results[J]. Injury, 2008, 39(Suppl 1):S50-S57.
4.	Swieszkowski W, Tuan BH, Kurzydlowski KJ, et al. Repair and regeneration of osteochondral defects in the articular joints[J]. Biomol Eng, 2007, 24(5):489-495.
5.	王秋玲, 吕玉明, 谢德明. 组织工程修复骨及软骨缺损的现状及展望[J]. 中国组织工程研究与临床康复, 2009, 13(37):7358-7362.
6.	Haasper C, Zeichen J, Meister R, et al. Tissue engineering of osteochondral constructs in vitro using bioreactors[J]. Injury, 2008, 39(Suppl 1):S66-S76.
7.	Schek RM, Taboas JM, Segvich SJ, et al. Engineered osteochondral grafts using biphasic composite solid free-form fabricated scaffolds[J]. Tissue Eng, 2004, 10(9/10):1376-1385.
8.	Martin I, Miot S, Barbero A, et al. Osteochondral tissue engineering[J]. J Biomech, 2007, 40(4):750-765.
9.	Holland TA, Bodde EW, Baggett LS, et al. Osteochondral repair in the rabbit model utilizing bilayered, degradable oligo[poly (ethylene glycol) fumarate] hydrogel scaffolds[J]. J Biomed Mater Res A, 2005, 75(1):156-167.
10.	Getgood AM, Kew SJ, Brooks R, et al. Evaluation of early-stage osteochondral defect repair using a biphasic scaffold based on a collagen-glycosaminoglycan biopolymer in a caprine model[J]. Knee, 2012, 19(4):422-430.
11.	Jiang CC, Chiang H, Liao CJ, et al. Repair of porcine articular cartilage defect with a biphasic osteochondral composite[J]. J Orthop Res, 2007, 25(10):1277-1290.
12.	Liljensten E, Adolfsson E, Strid KG, et al. Resorbable and nonresorbable hydroxyapatite granules as bone graft substitutes in rabbit cortical defects[J]. Clin Implant Dent Relat Res, 2003, 5(2):95-101.
13.	Jurgens WJ, Kroeze RJ, Zandieh-Doulabi B, et al. One-step surgical procedure for the treatment of osteochondral defects with adipose-derived stem cells in a caprine knee defect:a pilot study[J]. Biores Open Access, 2013, 2(4):315-325.
14.	Gao J, Dennis JE, Solchaga LA, et al. Repair of osteochondral defect with tissue-engineered two-phase composite material of injectable Calcium phosphate and hyaluronan sponge[J]. Tissue Eng, 2002, 8(5):827-837.
15.	Ho ST, Hutmacher DW, Ekaputra AK, et al. The evaluation of a biphasic osteochondral implant coupled with an electrospun membrane in a large animal model[J]. Tissue Eng Part A, 2010, 16(4):1123-1141.
16.	Pei M, He F, Boyce BM, et al. Repair of full-thickness femoral condyle cartilage defects using allogeneic synovial cell-engineered tissue constructs[J]. Osteoarthritis Cartilage, 2009, 17(6):714-722.
17.	张华亮, 王文良, 初殿伟, 等. 双层壳聚糖与HAP复合支架的初步研究[J]. 中国修复重建外科杂志, 2008, 22(11):1358-1363.
18.	Shao XX, Hutmacher DW, Ho ST, et al. Evaluation of a hybrid scaffold/cell construct in repair of high-load-bearing osteochondral defects in rabbits[J]. Biomaterials, 2006, 27(7):1071-1080.
19.	Arien-Zakay H, Lazarovici P, Nagler A. Tissue regeneration potential in human umbilical cord blood[J]. Best Pract Res Clin Haematol, 2010, 23(2):291-303.
20.	Rodrigues MT, Lee SJ, Gomes ME, et al. Bilayered constructs aimed at osteochondral strategies:the influence of medium supplements in the osteogenic and chondrogenic differentiation of amniotic fluid-derived stem cells[J]. Acta Biomater, 2012, 8(7):2795-2806.
21.	Im GI, Ahn JH, Kim SY, et al. A hyaluronate-atelocollagen/beta-tricalcium phosphate-hydroxyapatite biphasic scaffold for the repair of osteochondral defects:a porcine study[J]. Tissue Eng Part A, 2010, 16(4):1189-1200.
22.	Yang HN, Park JS, Woo DG, et al. Chondrogenesis of mesenchymal stem cells and dedifferentiated chondrocytes by transfection with SOX Trio genes[J]. Biomaterials, 2011, 32(30):7695-7704.
23.	Lam J, Lu S, Meretoja VV, et al. Generation of osteochondral tissue constructs with chondrogenically and osteogenically predifferentiated mesenchymal stem cells encapsulated in bilayered hydrogels[J]. Acta Biomater, 2014, 10(3):1112-1123.
24.	Li WJ, Chiang H, Kuo TF, et al. Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model:a pilot study[J]. J Tissue Eng Regen Med, 2009, 3(1):1-10.
25.	Sakata R, Kokubu T, Nagura I, et al. Localization of vascular endothelial growth factor during the early stages of osteochondral regeneration using a bioabsorbable synthetic polymer scaffold[J]. J Orthop Res, 2012, 30(2):252-259.
26.	Chimal-Monroy J, Díaz de León L. Differential effects of transforming growth factors beta 1, beta 2, beta 3 and beta 5 on chondrogenesis in mouse limb bud mesenchymal cells[J]. Int J Dev Biol, 1997, 41(1):91-102.
27.	Hunziker EB. Articular cartilage repair:are the intrinsic biological constraints undermining this process insuperable?[J]. Osteoarthritis Cartilage, 1999, 7(1):15-28.
28.	Minas T. The role of cartilage repair techniques, including chondrocyte transplantation, in focal chondral knee damage[J]. Instr Course Lect, 1999, 48:629-643.
29.	Jackson DW, Simon TM. Tissue engineering principles in orthopaedic surgery[J]. Clin Orthop Relat Res, 1999(367 Suppl):S31-S45.
30.	Vangsness CT, Kurzweil PR, Lieberman JR. Restoring articular cartilage in the knee[J]. Am J Orthop (Belle Mead NJ), 2004, 33(2 Supp2):29-34.
31.	Driesang IM, Hunziker EB. Delamination rates of tissue flaps used in articular cartilage repair[J]. J Orthop Res, 2000, 18(6):909-911.
32.	Guo X, Wang C, Duan C, et al. Repair of osteochondral defects with autologous chondrocytes seeded onto bioceramic scaffold in sheep[J]. Tissue Eng, 2005, 10(11/12):1830-1840.
33.	Wang X, Grogan SP, Rieser F, et al. Tissue engineering of biphasic cartilage constructs using various biodegradable scaffolds:an in vitro study[J]. Biomaterials, 2004, 25(17):3681-3688.
34.	Dormer NH, Berkland CJ, Detamore MS. Emerging techniques in stratified designs and continuous gradients for tissue engineering of interfaces[J]. Ann Biomed Eng, 2010, 38(6):2121-2141.
35.	Kon E, Delcogliano M, Filardo G, et al. Novel nano-composite multilayered biomaterial for osteochondral regeneration:a pilot clinical trial[J]. Am J Sports Med, 2011, 39(6):1180-1190.
36.	Kon E, Delcogliano M, Filardo G, et al. Novel nano-composite multi-layered biomaterial for the treatment of multifocal degenerative cartilage lesions[J]. Knee Surg Sports Traumatol Arthrosc, 2009, 17(11):1312-1315.
37.	Kon E, Delcogliano M, Filardo G, et al. A novel nano-composite multi-layered biomaterial for treatment of osteochondral lesions:technique note and an early stability pilot clinical trial[J]. Injury, 2010, 41(7):693-701.
38.	Mohan N, Dormer NH, Caldwell KL, et al. Continuous gradients of material composition and growth factors for effective regeneration of the osteochondral interface[J]. Tissue Eng Part A, 2011, 17(21/22):2845-2855.
39.	Liu C, Han Z, Czernuszka JT. Gradient collagen/nanohydroxyapatite composite scaffold:development and characterization[J]. Acta Biomater, 2009, 5(2):661-669.

1. Qi YY, Chen X, Jiang YZ, et al. Local delivery of autologous platelet in collagen matrix simulated in situ articular cartilage repair[J]. Cell Transplant, 2009, 18(10):1161-1169.
2. Chen WC, Yao CL, Wei YH, et al. Evaluating osteochondral defect repair potential of autologous rabbit bone marrow cells on type Ⅱ collagen scaffold[J]. Cytotechnology, 2011, 63(1):13-23.
3. Fritz J, Janssen P, Gaissmaier C, et al. Articular cartilage defects in the knee——basics, therapies and results[J]. Injury, 2008, 39(Suppl 1):S50-S57.
4. Swieszkowski W, Tuan BH, Kurzydlowski KJ, et al. Repair and regeneration of osteochondral defects in the articular joints[J]. Biomol Eng, 2007, 24(5):489-495.
5. 王秋玲, 吕玉明, 谢德明. 组织工程修复骨及软骨缺损的现状及展望[J]. 中国组织工程研究与临床康复, 2009, 13(37):7358-7362.
6. Haasper C, Zeichen J, Meister R, et al. Tissue engineering of osteochondral constructs in vitro using bioreactors[J]. Injury, 2008, 39(Suppl 1):S66-S76.
7. Schek RM, Taboas JM, Segvich SJ, et al. Engineered osteochondral grafts using biphasic composite solid free-form fabricated scaffolds[J]. Tissue Eng, 2004, 10(9/10):1376-1385.
8. Martin I, Miot S, Barbero A, et al. Osteochondral tissue engineering[J]. J Biomech, 2007, 40(4):750-765.
9. Holland TA, Bodde EW, Baggett LS, et al. Osteochondral repair in the rabbit model utilizing bilayered, degradable oligo[poly (ethylene glycol) fumarate] hydrogel scaffolds[J]. J Biomed Mater Res A, 2005, 75(1):156-167.
10. Getgood AM, Kew SJ, Brooks R, et al. Evaluation of early-stage osteochondral defect repair using a biphasic scaffold based on a collagen-glycosaminoglycan biopolymer in a caprine model[J]. Knee, 2012, 19(4):422-430.
11. Jiang CC, Chiang H, Liao CJ, et al. Repair of porcine articular cartilage defect with a biphasic osteochondral composite[J]. J Orthop Res, 2007, 25(10):1277-1290.
12. Liljensten E, Adolfsson E, Strid KG, et al. Resorbable and nonresorbable hydroxyapatite granules as bone graft substitutes in rabbit cortical defects[J]. Clin Implant Dent Relat Res, 2003, 5(2):95-101.
13. Jurgens WJ, Kroeze RJ, Zandieh-Doulabi B, et al. One-step surgical procedure for the treatment of osteochondral defects with adipose-derived stem cells in a caprine knee defect:a pilot study[J]. Biores Open Access, 2013, 2(4):315-325.
14. Gao J, Dennis JE, Solchaga LA, et al. Repair of osteochondral defect with tissue-engineered two-phase composite material of injectable Calcium phosphate and hyaluronan sponge[J]. Tissue Eng, 2002, 8(5):827-837.
15. Ho ST, Hutmacher DW, Ekaputra AK, et al. The evaluation of a biphasic osteochondral implant coupled with an electrospun membrane in a large animal model[J]. Tissue Eng Part A, 2010, 16(4):1123-1141.
16. Pei M, He F, Boyce BM, et al. Repair of full-thickness femoral condyle cartilage defects using allogeneic synovial cell-engineered tissue constructs[J]. Osteoarthritis Cartilage, 2009, 17(6):714-722.
17. 张华亮, 王文良, 初殿伟, 等. 双层壳聚糖与HAP复合支架的初步研究[J]. 中国修复重建外科杂志, 2008, 22(11):1358-1363.
18. Shao XX, Hutmacher DW, Ho ST, et al. Evaluation of a hybrid scaffold/cell construct in repair of high-load-bearing osteochondral defects in rabbits[J]. Biomaterials, 2006, 27(7):1071-1080.
19. Arien-Zakay H, Lazarovici P, Nagler A. Tissue regeneration potential in human umbilical cord blood[J]. Best Pract Res Clin Haematol, 2010, 23(2):291-303.
20. Rodrigues MT, Lee SJ, Gomes ME, et al. Bilayered constructs aimed at osteochondral strategies:the influence of medium supplements in the osteogenic and chondrogenic differentiation of amniotic fluid-derived stem cells[J]. Acta Biomater, 2012, 8(7):2795-2806.
21. Im GI, Ahn JH, Kim SY, et al. A hyaluronate-atelocollagen/beta-tricalcium phosphate-hydroxyapatite biphasic scaffold for the repair of osteochondral defects:a porcine study[J]. Tissue Eng Part A, 2010, 16(4):1189-1200.
22. Yang HN, Park JS, Woo DG, et al. Chondrogenesis of mesenchymal stem cells and dedifferentiated chondrocytes by transfection with SOX Trio genes[J]. Biomaterials, 2011, 32(30):7695-7704.
23. Lam J, Lu S, Meretoja VV, et al. Generation of osteochondral tissue constructs with chondrogenically and osteogenically predifferentiated mesenchymal stem cells encapsulated in bilayered hydrogels[J]. Acta Biomater, 2014, 10(3):1112-1123.
24. Li WJ, Chiang H, Kuo TF, et al. Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model:a pilot study[J]. J Tissue Eng Regen Med, 2009, 3(1):1-10.
25. Sakata R, Kokubu T, Nagura I, et al. Localization of vascular endothelial growth factor during the early stages of osteochondral regeneration using a bioabsorbable synthetic polymer scaffold[J]. J Orthop Res, 2012, 30(2):252-259.
26. Chimal-Monroy J, Díaz de León L. Differential effects of transforming growth factors beta 1, beta 2, beta 3 and beta 5 on chondrogenesis in mouse limb bud mesenchymal cells[J]. Int J Dev Biol, 1997, 41(1):91-102.
27. Hunziker EB. Articular cartilage repair:are the intrinsic biological constraints undermining this process insuperable?[J]. Osteoarthritis Cartilage, 1999, 7(1):15-28.
28. Minas T. The role of cartilage repair techniques, including chondrocyte transplantation, in focal chondral knee damage[J]. Instr Course Lect, 1999, 48:629-643.
29. Jackson DW, Simon TM. Tissue engineering principles in orthopaedic surgery[J]. Clin Orthop Relat Res, 1999(367 Suppl):S31-S45.
30. Vangsness CT, Kurzweil PR, Lieberman JR. Restoring articular cartilage in the knee[J]. Am J Orthop (Belle Mead NJ), 2004, 33(2 Supp2):29-34.
31. Driesang IM, Hunziker EB. Delamination rates of tissue flaps used in articular cartilage repair[J]. J Orthop Res, 2000, 18(6):909-911.
32. Guo X, Wang C, Duan C, et al. Repair of osteochondral defects with autologous chondrocytes seeded onto bioceramic scaffold in sheep[J]. Tissue Eng, 2005, 10(11/12):1830-1840.
33. Wang X, Grogan SP, Rieser F, et al. Tissue engineering of biphasic cartilage constructs using various biodegradable scaffolds:an in vitro study[J]. Biomaterials, 2004, 25(17):3681-3688.
34. Dormer NH, Berkland CJ, Detamore MS. Emerging techniques in stratified designs and continuous gradients for tissue engineering of interfaces[J]. Ann Biomed Eng, 2010, 38(6):2121-2141.
35. Kon E, Delcogliano M, Filardo G, et al. Novel nano-composite multilayered biomaterial for osteochondral regeneration:a pilot clinical trial[J]. Am J Sports Med, 2011, 39(6):1180-1190.
36. Kon E, Delcogliano M, Filardo G, et al. Novel nano-composite multi-layered biomaterial for the treatment of multifocal degenerative cartilage lesions[J]. Knee Surg Sports Traumatol Arthrosc, 2009, 17(11):1312-1315.
37. Kon E, Delcogliano M, Filardo G, et al. A novel nano-composite multi-layered biomaterial for treatment of osteochondral lesions:technique note and an early stability pilot clinical trial[J]. Injury, 2010, 41(7):693-701.
38. Mohan N, Dormer NH, Caldwell KL, et al. Continuous gradients of material composition and growth factors for effective regeneration of the osteochondral interface[J]. Tissue Eng Part A, 2011, 17(21/22):2845-2855.
39. Liu C, Han Z, Czernuszka JT. Gradient collagen/nanohydroxyapatite composite scaffold:development and characterization[J]. Acta Biomater, 2009, 5(2):661-669.

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组织工程双相支架修复关节软骨及软骨下骨缺损研究进展

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