• 四川大學(xué)華西醫(yī)院泌尿外科（成都，610041）;

目的綜述細(xì)胞外基質(zhì)（extracellular matrix，ECM）材料在組織工程中的研究現(xiàn)狀及臨床應(yīng)用進(jìn)展。 方法查閱近年來(lái)國(guó)內(nèi)外ECM材料制備方法、生物相容性、生物力學(xué)特性、可降解性能和臨床應(yīng)用等方面的相關(guān)文獻(xiàn)，并進(jìn)行分析總結(jié)。 結(jié)果ECM制備方法的改進(jìn)和免疫特性認(rèn)識(shí)的深入，為其用于組織的修復(fù)重建奠定了一定基礎(chǔ)。一系列動(dòng)物實(shí)驗(yàn)研究表明了小腸黏膜下層、膀胱ECM、脫細(xì)胞真皮等ECM材料應(yīng)用于尿道、膀胱、動(dòng)脈、皮膚等組織器官修復(fù)重建的可行性和有效性，顯示其具有廣闊的臨床應(yīng)用前景。 結(jié)論ECM材料是一種良好的生物衍生支架材料，有望成為組織修復(fù)重建中替代材料的重要來(lái)源。

引用本文： 員海超,蒲春曉,魏強(qiáng),韓平. 組織工程細(xì)胞外基質(zhì)材料研究進(jìn)展. 中國(guó)修復(fù)重建外科雜志, 2012, 26(10): 1251-1254. doi: 復(fù)制

1. Huebsh N, Moony DJ. Inspiration and application in the evolution of biomaterials. Nature, 2009, 462(7272): 426-432.
2. 羅靜聰, 楊志明, 李秀群, 等. 小腸黏膜下層細(xì)胞相容性的研究. 生物醫(yī)學(xué)工程學(xué)雜志, 2004, 21(5): 800-804.
3. 韓平, 宋超, 魏強(qiáng), 等. 組織工程膀胱細(xì)胞外基質(zhì)生物相容性的實(shí)驗(yàn)研究. 四川大學(xué)學(xué)報(bào): 醫(yī)學(xué)版, 2007, 38(6): 1009-1012.
4. 孔清泉, 高博, 幸?guī)V, 等. 以小腸黏膜下層為支架體外構(gòu)建組織工程軟骨的實(shí)驗(yàn)研究. 生物醫(yī)學(xué)工程學(xué)雜志, 2011, 28(3): 521-525.
5. Zhu WD, Xu YM, Feng C, et al. Different bladder defects reconstructed with bladder acellular matrix grafts in a rabbit model. Urologe A, 2011, 50(11): 1420-1425.
6. Gilbert TW, Sellaro TL, Badylak SF. Decellularization of tissues and organs. Biomaterials, 2006, 27(19): 3675-3683.
7. 羅靜聰, 楊志明. 小腸黏膜下層的制備及其特性的研究進(jìn)展. 中國(guó)修復(fù)重建外科雜志, 2003, 17(5): 425-428.
8. Luo JC, Chen W, Chen XH, et al. A multi-step method for preparation of porcine small intestinal submucosa (SIS). Biomaterials, 2011, 32(3): 706-713.
9. Raghavan D, Kropp BP, Lin HK, et al. Physical characteristics of small intestinal submucosa scaffolds are location-dependent. J Biomed Mater Res A, 2005, 73(1): 90-96.
10. Basile P, Dadali T, Jacobson J, et al. Freeze-dried tendon allografts as tissue-engineering scaffolds for Gdf5 gene delivery. Mol Ther, 2008, 16(3): 466-473.
11. Giannini S, Buda R, Caprio F, et al. Effects of freezing on the biomechanical and structural properties of human posterior tibial tendons. Int Orthop, 2008, 32(2): 145-151.
12. Ott HC, Matthiesen TS, Goh SK, et al. Perfusion-decellularized matrix: using nature, s platform to engineer a bioartificial heart. Nat Med, 2008, 14(2): 213-221.
13. 羅靜聰, 李秀群, 楊志明, 等. 脫細(xì)胞羊膜的制備及其生物相容性研究. 中國(guó)修復(fù)重建外科雜志, 2004, 18(2): 108-111.
14. Brown B, Lindberg K, Reing J, et al. The basement membrane component of biologic scaffolds derived from extracellular matrix. Tissue Eng, 2006, 12(3): 519-526.
15. Hodde JP, Record RD, Liang HA, et al. Vascular endothelial growth factor in porcine- derived extracellular matrix. Endothelium, 2001, 8(1): 11-24.
16. Joo KJ, Kim BS, Han JH, et al. Porcine vesical acellular matrix graft of tunica albuginea for penile reconstruction. Asian J Androl, 2006, 8(5): 543-548.
17. Chun SY, Lim GJ, Kwon TG, et al. Identification and characterization of bioactive factors in bladder submucosa matrix. Biomaterials, 2007, 28(29): 4251-4256.
18. Dahms SE, Piechota HJ, Dahiya R, et al. Composition and biomechanical properties of the bladder acellular matrix graft: comparative analysis in rat, pig and human. Br J Urol, 1998, 82(3): 411-419.
19. Freytes DO, Badylak SF, Webster TJ, et al. Biaxial strength of multilaminated extracellular matrix scaffolds. Biomaterials, 2004, 25(2): 2353-2361.
20. Badylak S, Kokini K, Tullius B, et al. Strength over time of a resorbable bioscaffold for body wall repair in a dog model. J Surg Res, 2001, 99(2): 282-287.
21. Gilbert TW, Stewart-Akers AM, Simmons-Byrd A, et al. Degradation and remodeling of small intestinal submucosa in canine Achilles tendon repair. J Bone Joint Surg (Am), 2007, 89(3): 621-630.
22. Valentin JE, Stewart-Akers AM, Gilbert TW, et al. Macrophage participation in the degradation and remodeling of extracellular matrix scaffolds. Tissue Eng Part A, 2009, 15(7): 1687-1694.
23. Deeken CR, Eliason BJ, Pichert MD, et al. Differentiation of biologic scaffold materials through physicomechanical, thermal, and enzymatic degradation techniques. Ann Surg, 2012, 255(3): 595-604.
24. Ferguson RE Jr, Pu LL. Repair of the abdominal donor-site fascial defect with small intestinal submucosa (Surgisis) after TRAM flap breast reconstruction. Ann Plast Surg, 2007, 58(1): 95-98.
25. Ansaloni L, Catena F, Gagliardi S, et al. Hernia repair with porcine small-intestinal submucosa. Hernia, 2007, 11(4): 321-326.
26. Ho KL, Witte MN, Bird ET. 8-ply small intestinal submucosa tension-free sling: spectrum of postoperative inflammation. J Urol, 2004, 171(1): 268-271.
27. Petter-Puchner AH, Fortelny RH, Mittermayr R, et al. Adverse effects of porcine small intestine submucosa implants in experimental ventral hernia repair. Surg Endosc, 2006, 20(6): 942-946.
28. McPherson TB, Liang H, Record RD, et al. Galalpha(1, 3)Gal epitope in porcine small intestinal submucosa. Tissue Eng, 2000, 6(3): 233-239.
29. Galili U, Clark MR, Shohet SB, et al. Evolutionary relationship between the natural anti-Gal antibody and the Gal alpha 1-3Gal epitope in primates. Proc Natl Acad Sci U S A, 1987, 84(5): 1369-1373.
30. Galili U, Shohet SB, Kobrin E, et al. Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol Chem, 1988, 263(33): 17755-17762.
31. Galili U, Rachmilewitz EA, Peleg A, et al. A unique natural human IgG antibody with anti-alpha-galactosyl specificity. J Exp Med, 1984, 160(5): 1519-1531.
32. Daly KA, Stewart-Akers AM, Hara H, et al. Effect of the alphaGal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model. Tissue Eng Part A, 2009, 15(12): 3877-3888.
33. Allman AJ, McPherson TB, Badylak SF, et al. Xenogeneic extracellular matrix grafts elicit a TH2-restricted immune response. Transplantation, 2001, 71(11): 1631-1640.
34. 黃翔, 羅靜聰, 廖勇, 等. 小腸黏膜下層修復(fù)尿道的實(shí)驗(yàn)研究. 中國(guó)修復(fù)重建外科雜志, 2006, 20(3): 206-209.
35. Kropp BP, Ludlow JK, Spicer D, et al. Rabbit urethral regeneration using small intestinal submucosa onlay grafts. Urology, 1998, 52(1): 138-142.
36. Badylak SF, Lantz GC, Coffey A, et al. Small intestinal submucosa as a large diameter vascular graft in the dog. J Surg Res, 1989, 47(1): 74-80.
37. Padalino MA, Castellani C, Dedja A, et al. Extracellular matrix graft for vascular reconstructive surgery: evidence of autologous regeneration of the neoaorta in a murine model. Eur J Cardiothorac Surg, 2012. [Epub ahead of print].
38. Ko R, Kazacos EA, Snyder S, et al. Tensile strength comparison of small intestinal submucosa body wall repair. J Surg Res, 2006, 135(1): 9-17.
39. Knoll LD. Use of small intestinal submucosa graft for the surgical management of Peyronie’s disease. J Urol, 2007, 178(6): 2474-2478.
40. Malcaeney HL, Bonar F, Murrell GA. Early inflammatory reaction after rotator cuff repair with a porcine small intestine submucosal implant: a report of 4 cases. Am J Sports Med, 2005, 33(6): 907-911.
41. Callcut RA, Schurr MJ, Sloan M, et al. Clinical experience with Alloderm: a one-staged composite dermal/epidermal replacement utilizing processed cadaver dermis and thin autografts. Burns, 2006, 32(5): 583-588.
42. Chen F, Yoo JJ, Atala A. Acellular collagen matrix as a possible “off the shelf” biomaterial for urethral repair. Urology, 1999, 54(3): 407-410.
43. el-Kassaby A, AbouShwared T, Atala A. Randomized comparative study between buccal mucosal and acellular bladder matrix grafts in complex anterior urethral strictures. J Urol, 2008, 179(4): 1432-1436.
44. Limpert JN, Desai AR, Kumpf AL, et al. Repair of abdominal wall defects with bovine pericardium. Am J Surg, 2009, 198(5): e60-655.
45. 鞠曉軍, 潘鋒, 柏樹(shù)令, 等. 人脫細(xì)胞羊膜復(fù)合脂肪源性干細(xì)胞修復(fù)大鼠全層皮膚缺損的實(shí)驗(yàn)研究. 中國(guó)修復(fù)重建外科雜志, 2010, 24(2): 143-149.
46. 胡云飛, 楊嗣星, 王玲瓏, 等. 尿道細(xì)胞外基質(zhì)在兔尿道重建中的應(yīng)用. 中華整形外科雜志, 2009, 25(1): 54-57.
  1. 1. Huebsh N, Moony DJ. Inspiration and application in the evolution of biomaterials. Nature, 2009, 462(7272): 426-432.
  2. 2. 羅靜聰, 楊志明, 李秀群, 等. 小腸黏膜下層細(xì)胞相容性的研究. 生物醫(yī)學(xué)工程學(xué)雜志, 2004, 21(5): 800-804.
  3. 3. 韓平, 宋超, 魏強(qiáng), 等. 組織工程膀胱細(xì)胞外基質(zhì)生物相容性的實(shí)驗(yàn)研究. 四川大學(xué)學(xué)報(bào): 醫(yī)學(xué)版, 2007, 38(6): 1009-1012.
  4. 4. 孔清泉, 高博, 幸?guī)V, 等. 以小腸黏膜下層為支架體外構(gòu)建組織工程軟骨的實(shí)驗(yàn)研究. 生物醫(yī)學(xué)工程學(xué)雜志, 2011, 28(3): 521-525.
  5. 5. Zhu WD, Xu YM, Feng C, et al. Different bladder defects reconstructed with bladder acellular matrix grafts in a rabbit model. Urologe A, 2011, 50(11): 1420-1425.
  6. 6. Gilbert TW, Sellaro TL, Badylak SF. Decellularization of tissues and organs. Biomaterials, 2006, 27(19): 3675-3683.
  7. 7. 羅靜聰, 楊志明. 小腸黏膜下層的制備及其特性的研究進(jìn)展. 中國(guó)修復(fù)重建外科雜志, 2003, 17(5): 425-428.
  8. 8. Luo JC, Chen W, Chen XH, et al. A multi-step method for preparation of porcine small intestinal submucosa (SIS). Biomaterials, 2011, 32(3): 706-713.
  9. 9. Raghavan D, Kropp BP, Lin HK, et al. Physical characteristics of small intestinal submucosa scaffolds are location-dependent. J Biomed Mater Res A, 2005, 73(1): 90-96.
  10. 10. Basile P, Dadali T, Jacobson J, et al. Freeze-dried tendon allografts as tissue-engineering scaffolds for Gdf5 gene delivery. Mol Ther, 2008, 16(3): 466-473.
  11. 11. Giannini S, Buda R, Caprio F, et al. Effects of freezing on the biomechanical and structural properties of human posterior tibial tendons. Int Orthop, 2008, 32(2): 145-151.
  12. 12. Ott HC, Matthiesen TS, Goh SK, et al. Perfusion-decellularized matrix: using nature, s platform to engineer a bioartificial heart. Nat Med, 2008, 14(2): 213-221.
  13. 13. 羅靜聰, 李秀群, 楊志明, 等. 脫細(xì)胞羊膜的制備及其生物相容性研究. 中國(guó)修復(fù)重建外科雜志, 2004, 18(2): 108-111.
  14. 14. Brown B, Lindberg K, Reing J, et al. The basement membrane component of biologic scaffolds derived from extracellular matrix. Tissue Eng, 2006, 12(3): 519-526.
  15. 15. Hodde JP, Record RD, Liang HA, et al. Vascular endothelial growth factor in porcine- derived extracellular matrix. Endothelium, 2001, 8(1): 11-24.
  16. 16. Joo KJ, Kim BS, Han JH, et al. Porcine vesical acellular matrix graft of tunica albuginea for penile reconstruction. Asian J Androl, 2006, 8(5): 543-548.
  17. 17. Chun SY, Lim GJ, Kwon TG, et al. Identification and characterization of bioactive factors in bladder submucosa matrix. Biomaterials, 2007, 28(29): 4251-4256.
  18. 18. Dahms SE, Piechota HJ, Dahiya R, et al. Composition and biomechanical properties of the bladder acellular matrix graft: comparative analysis in rat, pig and human. Br J Urol, 1998, 82(3): 411-419.
  19. 19. Freytes DO, Badylak SF, Webster TJ, et al. Biaxial strength of multilaminated extracellular matrix scaffolds. Biomaterials, 2004, 25(2): 2353-2361.
  20. 20. Badylak S, Kokini K, Tullius B, et al. Strength over time of a resorbable bioscaffold for body wall repair in a dog model. J Surg Res, 2001, 99(2): 282-287.
  21. 21. Gilbert TW, Stewart-Akers AM, Simmons-Byrd A, et al. Degradation and remodeling of small intestinal submucosa in canine Achilles tendon repair. J Bone Joint Surg (Am), 2007, 89(3): 621-630.
  22. 22. Valentin JE, Stewart-Akers AM, Gilbert TW, et al. Macrophage participation in the degradation and remodeling of extracellular matrix scaffolds. Tissue Eng Part A, 2009, 15(7): 1687-1694.
  23. 23. Deeken CR, Eliason BJ, Pichert MD, et al. Differentiation of biologic scaffold materials through physicomechanical, thermal, and enzymatic degradation techniques. Ann Surg, 2012, 255(3): 595-604.
  24. 24. Ferguson RE Jr, Pu LL. Repair of the abdominal donor-site fascial defect with small intestinal submucosa (Surgisis) after TRAM flap breast reconstruction. Ann Plast Surg, 2007, 58(1): 95-98.
  25. 25. Ansaloni L, Catena F, Gagliardi S, et al. Hernia repair with porcine small-intestinal submucosa. Hernia, 2007, 11(4): 321-326.
  26. 26. Ho KL, Witte MN, Bird ET. 8-ply small intestinal submucosa tension-free sling: spectrum of postoperative inflammation. J Urol, 2004, 171(1): 268-271.
  27. 27. Petter-Puchner AH, Fortelny RH, Mittermayr R, et al. Adverse effects of porcine small intestine submucosa implants in experimental ventral hernia repair. Surg Endosc, 2006, 20(6): 942-946.
  28. 28. McPherson TB, Liang H, Record RD, et al. Galalpha(1, 3)Gal epitope in porcine small intestinal submucosa. Tissue Eng, 2000, 6(3): 233-239.
  29. 29. Galili U, Clark MR, Shohet SB, et al. Evolutionary relationship between the natural anti-Gal antibody and the Gal alpha 1-3Gal epitope in primates. Proc Natl Acad Sci U S A, 1987, 84(5): 1369-1373.
  30. 30. Galili U, Shohet SB, Kobrin E, et al. Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol Chem, 1988, 263(33): 17755-17762.
  31. 31. Galili U, Rachmilewitz EA, Peleg A, et al. A unique natural human IgG antibody with anti-alpha-galactosyl specificity. J Exp Med, 1984, 160(5): 1519-1531.
  32. 32. Daly KA, Stewart-Akers AM, Hara H, et al. Effect of the alphaGal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model. Tissue Eng Part A, 2009, 15(12): 3877-3888.
  33. 33. Allman AJ, McPherson TB, Badylak SF, et al. Xenogeneic extracellular matrix grafts elicit a TH2-restricted immune response. Transplantation, 2001, 71(11): 1631-1640.
  34. 34. 黃翔, 羅靜聰, 廖勇, 等. 小腸黏膜下層修復(fù)尿道的實(shí)驗(yàn)研究. 中國(guó)修復(fù)重建外科雜志, 2006, 20(3): 206-209.
  35. 35. Kropp BP, Ludlow JK, Spicer D, et al. Rabbit urethral regeneration using small intestinal submucosa onlay grafts. Urology, 1998, 52(1): 138-142.
  36. 36. Badylak SF, Lantz GC, Coffey A, et al. Small intestinal submucosa as a large diameter vascular graft in the dog. J Surg Res, 1989, 47(1): 74-80.
  37. 37. Padalino MA, Castellani C, Dedja A, et al. Extracellular matrix graft for vascular reconstructive surgery: evidence of autologous regeneration of the neoaorta in a murine model. Eur J Cardiothorac Surg, 2012. [Epub ahead of print].
  38. 38. Ko R, Kazacos EA, Snyder S, et al. Tensile strength comparison of small intestinal submucosa body wall repair. J Surg Res, 2006, 135(1): 9-17.
  39. 39. Knoll LD. Use of small intestinal submucosa graft for the surgical management of Peyronie’s disease. J Urol, 2007, 178(6): 2474-2478.
  40. 40. Malcaeney HL, Bonar F, Murrell GA. Early inflammatory reaction after rotator cuff repair with a porcine small intestine submucosal implant: a report of 4 cases. Am J Sports Med, 2005, 33(6): 907-911.
  41. 41. Callcut RA, Schurr MJ, Sloan M, et al. Clinical experience with Alloderm: a one-staged composite dermal/epidermal replacement utilizing processed cadaver dermis and thin autografts. Burns, 2006, 32(5): 583-588.
  42. 42. Chen F, Yoo JJ, Atala A. Acellular collagen matrix as a possible “off the shelf” biomaterial for urethral repair. Urology, 1999, 54(3): 407-410.
  43. 43. el-Kassaby A, AbouShwared T, Atala A. Randomized comparative study between buccal mucosal and acellular bladder matrix grafts in complex anterior urethral strictures. J Urol, 2008, 179(4): 1432-1436.
  44. 44. Limpert JN, Desai AR, Kumpf AL, et al. Repair of abdominal wall defects with bovine pericardium. Am J Surg, 2009, 198(5): e60-655.
  45. 45. 鞠曉軍, 潘鋒, 柏樹(shù)令, 等. 人脫細(xì)胞羊膜復(fù)合脂肪源性干細(xì)胞修復(fù)大鼠全層皮膚缺損的實(shí)驗(yàn)研究. 中國(guó)修復(fù)重建外科雜志, 2010, 24(2): 143-149.
  46. 46. 胡云飛, 楊嗣星, 王玲瓏, 等. 尿道細(xì)胞外基質(zhì)在兔尿道重建中的應(yīng)用. 中華整形外科雜志, 2009, 25(1): 54-57.