• 第三軍醫(yī)大學(xué)西南醫(yī)院關(guān)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(jìn)行綜述，并對其發(fā)展前景進(jìn)行展望。 方法廣泛查閱近年來關(guān)節(jié)軟骨組織工程支架的相關(guān)文獻(xiàn)，并對多種天然生物支架材料和人工合成支架材料的相關(guān)實(shí)驗(yàn)及臨床應(yīng)用效果進(jìn)行分析總結(jié)。 結(jié)果軟骨組織工程支架的設(shè)計對軟骨組織損傷修復(fù)成功與否至關(guān)重要，理想的軟骨支架可以引導(dǎo)并促進(jìn)新生軟骨組織的形成。目前所應(yīng)用的支架材料均有其局限性。 結(jié)論進(jìn)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(fù)具有重要意義。

引用本文： 劉清宇,王富友,楊柳. 關(guān)節(jié)軟骨組織工程支架的研究進(jìn)展. 中國修復(fù)重建外科雜志, 2012, 26(10): 1247-1250. doi: 復(fù)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(fù)兔膝關(guān)節(jié)軟骨缺損的實(shí)驗(yàn)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(fù)合培養(yǎng)物植入修復(fù)兔關(guān)節(jié)軟骨缺損的實(shí)驗(yàn)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(jìn)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(gòu)建. 解放軍醫(yī)學(xué)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(xì)胞復(fù)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(fù)兔膝關(guān)節(jié)軟骨缺損的實(shí)驗(yàn)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(fù)合培養(yǎng)物植入修復(fù)兔關(guān)節(jié)軟骨缺損的實(shí)驗(yàn)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(jìn)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(gòu)建. 解放軍醫(yī)學(xué)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(xì)胞復(fù)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.