• 第三軍醫(yī)大學西南醫(yī)院關節(jié)外科中心（重慶，400038）;

目的對軟骨組織工程支架材料的研究現(xiàn)狀進行綜述，并對其發(fā)展前景進行展望。 方法廣泛查閱近年來關節(jié)軟骨組織工程支架的相關文獻，并對多種天然生物支架材料和人工合成支架材料的相關實驗及臨床應用效果進行分析總結。 結果軟骨組織工程支架的設計對軟骨組織損傷修復成功與否至關重要，理想的軟骨支架可以引導并促進新生軟骨組織的形成。目前所應用的支架材料均有其局限性。 結論進一步深入研究軟骨組織工程支架，對未來臨床軟骨損傷的修復具有重要意義。

引用本文： 劉清宇,王富友,楊柳. 關節(jié)軟骨組織工程支架的研究進展. 中國修復重建外科雜志, 2012, 26(10): 1247-1250. doi: 復制

1. Poole CA. Articular cartilage chondrons: form, function and failure. J Anat, 1997, 191(Pt 1): 1-13.
2. Mcnickle AG, Provencher MT, Cole BJ. Overview of existing cartilage repair technology. Sports Med Arthrosc, 2008, 16(4): 196-201.
3. Thiede RM, Lu Y, Markel MD. A review of the treatment methods for cartilage defects. Vet Comp Orthop Traumatol, 2012, 25(4): 263-272.
4. Hurtig M, Pearce S, Warren S, et al. Arthroscopic mosaic arthroplasty in the equine third carpal bone. Vet Surg, 2001, 30(3): 228-239.
5. Solheim E, Hegna J, Oyen J, et al. Osteochondral autografting (mosaicplasty) in articular cartilage defects in the knee: results at 5 to 9 years. Knee, 2010, 17(1): 84-87.
6. Bugbee WD. Fresh osteochondral allografts. J Knee Surg, 2002, 15(3): 191-195.
7. Stevenson S, Dannucci GA, Sharkey NA, et al. The fate of articular cartilage after transplantation of fresh and cryopreserved tissue-antigen-matched and mismatched osteochondral allografts in dogs. J Bone Joint Surg (Am), 1989, 71(9): 1297-1307.
8. Danisovic L, Varga I, Zamborsky R, et al. The tissue engineering of articular cartilage: cells, scaffolds and stimulating factors. Exp Biol Med (Maywood), 2012, 237(1): 10-17.
9. Chung C, Burdick JA. Engineering cartilage tissue. Adv Drug Deliv Rev, 2008, 60(2): 243-262.
10. Bryant SJ, Anseth KS. Controlling the spatial distribution of ECM components in degradable PEG hydrogels for tissue engineering cartilage. J Biomed Mater Res A, 2003, 64(1): 70-79.
11. Yang Q, Peng J, Guo Q, et al. A cartilage ECM-derived 3-D porous acellular matrix scaffold for in vivo cartilage tissue engineering with PKH26-labeled chondrogenic bone marrow-derived mesenchymal stem cells. Biomaterials, 2008, 29(15): 2378-2387.
12. Wang Y, Bella E, Lee CS, et al. The synergistic effects of 3-D porous silk fibroin matrix scaffold properties and hydrodynamic environment in cartilage tissue regeneration. Biomaterials, 2010, 31(17): 4672-4681.
13. Gong YY, Xue JX, Zhang WJ, et al. A sandwich model for engineering cartilage with acellular cartilage sheets and chondrocytes. Biomaterials, 2011, 32(9): 2265-2273.
14. Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials, 2011, 32(12): 3233-3243.
15. Grande DA, Halberstadt C, Naughton G, et al. Evaluation of matrix scaffolds for tissue engineering of articular cartilage grafts. J Biomed Mater Res, 1997, 34(2): 211-220.
16. 李斯明, 楊小紅, 方力, 等. 高純度豬軟骨Ⅱ型膠原修復兔膝關節(jié)軟骨缺損的實驗研究. 中華創(chuàng)傷骨科雜志, 2008, 10(9): 844-849.
17. Wakitani S, Goto T, Pineda SJ, et al. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg (Am), 1994, 76(4): 579-592.
18. Chenite A, Chaput C, Wang D, et al. Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials, 2000, 21(21): 2155-2161.
19. Montembault A, Tahiri K, Korwin-Zmijowska C, et al. A material decoy of biological media based on chitosan physical hydrogels: application to cartilage tissue engineering. Biochimie, 2006, 88(5): 551-564.
20. Toh WS, Lee EH, Guo XM, et al. Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells. Biomaterials, 2010, 31(27): 6968-6980.
21. Stok KS, Lisignoli G, Cristino S, et al. Mechano-functional assessment of human mesenchymal stem cells grown in three-dimensional hyaluronan-based scaffolds for cartilage tissue engineering. J Biomed Mater Res A, 2010, 93(1): 37-45.
22. Wang W, Li B, Yang J, et al. The restoration of full-thickness cartilage defects with BMSCs and TGF-beta 1 loaded PLGA/fibrin gel constructs. Biomaterials, 2010, 31(34): 8964-8973.
23. Hendrickson DA, Nixon AJ, Grande DA, et al. Chondrocyte-fibrin matrix transplants for resurfacing extensive articular cartilage defects. J Orthop Res, 1994, 12(4): 485-497.
24. Dare EV, Griffith M, Poitras P, et al. Fibrin sealants from fresh or fresh/frozen plasma as scaffolds for in vitro articular cartilage regeneration. Tissue Eng Part A, 2009, 15(8): 2285-2297.
25. Kawabe N, Yoshinao M. The repair of full-thickness articular cartilage defects. Immune responses to reparative tissue formed by allogeneic growth plate chondrocyte implants. Clin Orthop Relat Res, 1991, (268): 279-293.
26. Kawakami M, Tomita N, Shimada Y, et al. Chondrocyte distribution and cartilage regeneration in silk fibroin sponge. Biomed Mater Eng, 2011, 21(1): 53-61.
27. Wooley PH, Morren R, Andary J, et al. Inflammatory responses to orthopaedic biomaterials in the murine air pouch. Biomaterials, 2002, 23(2): 517-526.
28. Wang CC, Yang KC, Lin KH, et al. Cartilage regeneration in SCID mice using a highly organized three-dimensional alginate scaffold. Biomaterials, 2012, 33(1): 120-127.
29. 張軍軍, 任龍喜, 程愛國, 等. PLA-MSCs復合培養(yǎng)物植入修復兔關節(jié)軟骨缺損的實驗研究. 中國骨腫瘤骨病, 2005, 4(5): 293-296.
30. Chu CR, Coutts RD, Yoshioka M, et al. Articular cartilage repair using allogeneic perichondrocyte-seeded biodegradable porous polylactic acid (PLA): a tissue-engineering study. J Biomed Mater Res, 1995, 29(9): 1147-1154.
31. 陳莉, 趙保中, 杜錫光. 聚羥基乙酸及其共聚物的研究進展. 化工新型材料, 2002, 30(3): 11-15.
32. 孫安科, 陳文弦, 崔鵬程, 等. 以PGA為三維支架同種異體工程化軟骨的構建. 解放軍醫(yī)學雜志, 2001, 26(10): 748-749.
33. El Sayed K, Marzahn U, John T, et al. PGA-associated heterotopic chondrocyte cocultures: implications of nasoseptal and auricular chondrocytes in articular cartilage repair. J Tissue Eng Regen Med, 2011. [Epub ahead of print].
34. 張路, 李瓊, 周廣東, 等. 不同比例的PLA-PGA支架對軟骨細胞復合的影響. 組織工程與重建外科, 2008, 4(6): 305-307.
35. Cohen SB, Meirisch CM, Wilson HA, et al. The use of absorbable co-polymer pads with alginate and cells for articular cartilage repair in rabbits. Biomaterials, 2003, 24(15): 2653-2660.
36. Zhao H, Ma L, Gao C, et al. A composite scaffold of PLGA microspheres/fibrin gel for cartilage tissue engineering: fabrication, physical properties, and cell responsiveness. J Biomed Mater Res B Appl Biomater, 2009, 88(1): 240-249.
37. Ti?li RS, Gümü?derelio?lu M. Evaluation of alginate-chitosan semi IPNs as cartilage scaffolds. J Mater Sci Mater Med, 2009, 20(3): 699-709.
38. Laurens E, Schneider E, Winalski CS, et al. A synthetic cartilage extracellular matrix model: hyaluronan and collagen hydrogel relaxivity, impact of macromolecular concentration on dGEMRIC. Skeletal Radiol, 2012, 41(2): 209-217.
39. Bhardwaj N, Nguyen QT, Chen AC, et al. Potential of 3-D tissue constructs engineered from bovine chondrocytes/silk fibroin-chitosan for in vitro cartilage tissue engineering. Biomaterials, 2011, 32(25): 5773-5781.
  1. 1. Poole CA. Articular cartilage chondrons: form, function and failure. J Anat, 1997, 191(Pt 1): 1-13.
  2. 2. Mcnickle AG, Provencher MT, Cole BJ. Overview of existing cartilage repair technology. Sports Med Arthrosc, 2008, 16(4): 196-201.
  3. 3. Thiede RM, Lu Y, Markel MD. A review of the treatment methods for cartilage defects. Vet Comp Orthop Traumatol, 2012, 25(4): 263-272.
  4. 4. Hurtig M, Pearce S, Warren S, et al. Arthroscopic mosaic arthroplasty in the equine third carpal bone. Vet Surg, 2001, 30(3): 228-239.
  5. 5. Solheim E, Hegna J, Oyen J, et al. Osteochondral autografting (mosaicplasty) in articular cartilage defects in the knee: results at 5 to 9 years. Knee, 2010, 17(1): 84-87.
  6. 6. Bugbee WD. Fresh osteochondral allografts. J Knee Surg, 2002, 15(3): 191-195.
  7. 7. Stevenson S, Dannucci GA, Sharkey NA, et al. The fate of articular cartilage after transplantation of fresh and cryopreserved tissue-antigen-matched and mismatched osteochondral allografts in dogs. J Bone Joint Surg (Am), 1989, 71(9): 1297-1307.
  8. 8. Danisovic L, Varga I, Zamborsky R, et al. The tissue engineering of articular cartilage: cells, scaffolds and stimulating factors. Exp Biol Med (Maywood), 2012, 237(1): 10-17.
  9. 9. Chung C, Burdick JA. Engineering cartilage tissue. Adv Drug Deliv Rev, 2008, 60(2): 243-262.
  10. 10. Bryant SJ, Anseth KS. Controlling the spatial distribution of ECM components in degradable PEG hydrogels for tissue engineering cartilage. J Biomed Mater Res A, 2003, 64(1): 70-79.
  11. 11. Yang Q, Peng J, Guo Q, et al. A cartilage ECM-derived 3-D porous acellular matrix scaffold for in vivo cartilage tissue engineering with PKH26-labeled chondrogenic bone marrow-derived mesenchymal stem cells. Biomaterials, 2008, 29(15): 2378-2387.
  12. 12. Wang Y, Bella E, Lee CS, et al. The synergistic effects of 3-D porous silk fibroin matrix scaffold properties and hydrodynamic environment in cartilage tissue regeneration. Biomaterials, 2010, 31(17): 4672-4681.
  13. 13. Gong YY, Xue JX, Zhang WJ, et al. A sandwich model for engineering cartilage with acellular cartilage sheets and chondrocytes. Biomaterials, 2011, 32(9): 2265-2273.
  14. 14. Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials, 2011, 32(12): 3233-3243.
  15. 15. Grande DA, Halberstadt C, Naughton G, et al. Evaluation of matrix scaffolds for tissue engineering of articular cartilage grafts. J Biomed Mater Res, 1997, 34(2): 211-220.
  16. 16. 李斯明, 楊小紅, 方力, 等. 高純度豬軟骨Ⅱ型膠原修復兔膝關節(jié)軟骨缺損的實驗研究. 中華創(chuàng)傷骨科雜志, 2008, 10(9): 844-849.
  17. 17. Wakitani S, Goto T, Pineda SJ, et al. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg (Am), 1994, 76(4): 579-592.
  18. 18. Chenite A, Chaput C, Wang D, et al. Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials, 2000, 21(21): 2155-2161.
  19. 19. Montembault A, Tahiri K, Korwin-Zmijowska C, et al. A material decoy of biological media based on chitosan physical hydrogels: application to cartilage tissue engineering. Biochimie, 2006, 88(5): 551-564.
  20. 20. Toh WS, Lee EH, Guo XM, et al. Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells. Biomaterials, 2010, 31(27): 6968-6980.
  21. 21. Stok KS, Lisignoli G, Cristino S, et al. Mechano-functional assessment of human mesenchymal stem cells grown in three-dimensional hyaluronan-based scaffolds for cartilage tissue engineering. J Biomed Mater Res A, 2010, 93(1): 37-45.
  22. 22. Wang W, Li B, Yang J, et al. The restoration of full-thickness cartilage defects with BMSCs and TGF-beta 1 loaded PLGA/fibrin gel constructs. Biomaterials, 2010, 31(34): 8964-8973.
  23. 23. Hendrickson DA, Nixon AJ, Grande DA, et al. Chondrocyte-fibrin matrix transplants for resurfacing extensive articular cartilage defects. J Orthop Res, 1994, 12(4): 485-497.
  24. 24. Dare EV, Griffith M, Poitras P, et al. Fibrin sealants from fresh or fresh/frozen plasma as scaffolds for in vitro articular cartilage regeneration. Tissue Eng Part A, 2009, 15(8): 2285-2297.
  25. 25. Kawabe N, Yoshinao M. The repair of full-thickness articular cartilage defects. Immune responses to reparative tissue formed by allogeneic growth plate chondrocyte implants. Clin Orthop Relat Res, 1991, (268): 279-293.
  26. 26. Kawakami M, Tomita N, Shimada Y, et al. Chondrocyte distribution and cartilage regeneration in silk fibroin sponge. Biomed Mater Eng, 2011, 21(1): 53-61.
  27. 27. Wooley PH, Morren R, Andary J, et al. Inflammatory responses to orthopaedic biomaterials in the murine air pouch. Biomaterials, 2002, 23(2): 517-526.
  28. 28. Wang CC, Yang KC, Lin KH, et al. Cartilage regeneration in SCID mice using a highly organized three-dimensional alginate scaffold. Biomaterials, 2012, 33(1): 120-127.
  29. 29. 張軍軍, 任龍喜, 程愛國, 等. PLA-MSCs復合培養(yǎng)物植入修復兔關節(jié)軟骨缺損的實驗研究. 中國骨腫瘤骨病, 2005, 4(5): 293-296.
  30. 30. Chu CR, Coutts RD, Yoshioka M, et al. Articular cartilage repair using allogeneic perichondrocyte-seeded biodegradable porous polylactic acid (PLA): a tissue-engineering study. J Biomed Mater Res, 1995, 29(9): 1147-1154.
  31. 31. 陳莉, 趙保中, 杜錫光. 聚羥基乙酸及其共聚物的研究進展. 化工新型材料, 2002, 30(3): 11-15.
  32. 32. 孫安科, 陳文弦, 崔鵬程, 等. 以PGA為三維支架同種異體工程化軟骨的構建. 解放軍醫(yī)學雜志, 2001, 26(10): 748-749.
  33. 33. El Sayed K, Marzahn U, John T, et al. PGA-associated heterotopic chondrocyte cocultures: implications of nasoseptal and auricular chondrocytes in articular cartilage repair. J Tissue Eng Regen Med, 2011. [Epub ahead of print].
  34. 34. 張路, 李瓊, 周廣東, 等. 不同比例的PLA-PGA支架對軟骨細胞復合的影響. 組織工程與重建外科, 2008, 4(6): 305-307.
  35. 35. Cohen SB, Meirisch CM, Wilson HA, et al. The use of absorbable co-polymer pads with alginate and cells for articular cartilage repair in rabbits. Biomaterials, 2003, 24(15): 2653-2660.
  36. 36. Zhao H, Ma L, Gao C, et al. A composite scaffold of PLGA microspheres/fibrin gel for cartilage tissue engineering: fabrication, physical properties, and cell responsiveness. J Biomed Mater Res B Appl Biomater, 2009, 88(1): 240-249.
  37. 37. Ti?li RS, Gümü?derelio?lu M. Evaluation of alginate-chitosan semi IPNs as cartilage scaffolds. J Mater Sci Mater Med, 2009, 20(3): 699-709.
  38. 38. Laurens E, Schneider E, Winalski CS, et al. A synthetic cartilage extracellular matrix model: hyaluronan and collagen hydrogel relaxivity, impact of macromolecular concentration on dGEMRIC. Skeletal Radiol, 2012, 41(2): 209-217.
  39. 39. Bhardwaj N, Nguyen QT, Chen AC, et al. Potential of 3-D tissue constructs engineered from bovine chondrocytes/silk fibroin-chitosan for in vitro cartilage tissue engineering. Biomaterials, 2011, 32(25): 5773-5781.