脱细胞技术及其在组织工程中的应用研究进展_《中国修复重建外科杂志》

作者：

赵宇 ^1,2 , 于淼 ² , 柏树令 ²

1中国医科大学附属盛京医院整形美容外科（沈阳，110004）;;
2中国医科大学基础医学院组织工程教研室;

关键词：

组织工程支架细胞外基质脱细胞灭菌

DOI：

10.7507/1002-1892.20130207

视频：

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摘要 全文 图表 视频 参考文献 施引文献 补充材料

目的对获取组织细胞外基质（extracellular matrix，ECM）的脱细胞方法及脱细胞ECM支架在组织工程领域的应用进行综述。方法查阅近年国内外相关文献，对脱细胞方法进行归纳和分类，分析灭菌方法对脱细胞支架的影响，提出脱细胞程度的评价标准，总结脱细胞ECM支架在不同组织器官中的应用。结果脱细胞方法主要有物理法、化学试剂法和生物制剂法，不同的脱细胞方法对细胞去除程度及ECM成分的影响不同，需要根据组织和脱细胞方法的特点选择最佳脱细胞方法，以达到理想效果。结论选择合适的脱细胞方法对制备组织工程所需的生物材料非常重要。

引用本文： 赵宇,于淼,柏树令. 脱细胞技术及其在组织工程中的应用研究进展. 中国修复重建外科杂志, 2013, 27(8): 950-954. doi: 10.7507/1002-1892.20130207 复制

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2.	Weber B, Emmert MY, Schoenauer R, et al. Tissue engineering on matrix: future of autologous tissue replacement. Semin Immunopathol, 2011, 33(3): 307-315.
3.	Flynn LE. The use of decellularized adipose tissue to provide an inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells. Biomaterials, 2010, 31(17): 4715-4724.
4.	Francis MP, Sachs PC, Madurantakam PA, et al. Electrospinning adipose tissue-derived extracellular matrix for adipose stem cell culture. J Biomed Mater Res A, 2012, 100(7): 1716-1724.
5.	江燕林, 张忆, 杨洁亮, 等. 脱细胞小牛肌腱组织形态学和生物力学特性研究. 中国修复重建外科杂志, 2013, 27(5): 552-553.
6.	Hopkinson A, Shanmuganathan VA, Gray T, et al. Optimization of amniotic membrane (AM) denuding for tissue engineering. Tissue Eng Part C Methods, 2008, 14(4): 371-381.
7.	Funamoto S, Nam K, Kimura T, et al. The use of high-hydrostatic pressure treatment to decellularize blood vessels. Biomaterials, 2010, 31(13): 3590-3595.
8.	Negishi J, Funamoto S, Kimura T, et al. Porcine radial artery decellularization by high hydrostatic pressure. J Tissue Eng Regen Med, 2012. [Epub ahead of print].
9.	Phillips M, Maor E, Rubinsky B. Nonthermal irreversible electroporation for tissue decellularization. J Biomech Eng, 2010, 132(9): 091003.
10.	Alhamdani MS, Schroder C, Werner J, et al. Single-step procedure for the isolation of proteins at near-native conditions from mammalian tissue for proteomic analysis on antibody microarrays. J Proteome Res, 2010, 9(2): 963-971.
11.	Du L, Wu X, Pang K, et al. Histological evaluation and biomechanical characterisation of an acellular porcine cornea scaffold. Br J Ophthalmol, 2011, 95(3): 410-414.
12.	Sicari BM, Johnson SA, Siu BF, et al. The effect of source animal age upon the in vivo remodeling characteristics of an extracellular matrix scaffold. Biomaterials, 2012, 33(22): 5524-5533.
13.	Ren H, Shi X, Tao L, et al. Evaluation of two decellularization methods in the development of a whole-organ decellularized rat liver scaffold. Liver Int, 2013, 33(3): 448-458.
14.	Sullivan DC, Mirmalek-Sani SH, Deegan DB, et al. Decellularization methods of porcine kidneys for whole organ engineering using a high-throughput system. Biomaterials, 2012, 33(31): 7756-7764.
15.	Petersen TH, Calle EA, Zhao L, et al. Tissue-engineered lungs for in vivo implantation. Science, 2010, 329(5991): 538-541.
16.	Hudson TW, Liu SY, Schmidt CE. Engineering an improved acellular nerve graft via optimized chemical processing. Tissue Eng, 2004, 10(9-10): 1346-1358.
17.	Cebotari S, Tudorache I, Jaekel T, et al. Detergent decellularization of heart valves for tissue engineering: toxicological effects of residual detergents on human endothelial cells. Artif Organs, 2010, 34(3): 206-210.
18.	Meyer SR, Chiu B, Churchill TA, et al. Comparison of aortic valve allograft decellularization techniques in the rat. J Biomed Mater Res A, 2006, 79(2): 254-262.
19.	Deeken CR, White AK, Bachman SL, et al. Method of preparing a decellularized porcine tendon using tributyl phosphate. J Biomed Mater Res B Appl Biomater, 2011, 96(2): 199-206.
20.	Dong X, Wei X, Yi W, et al. RGD-modified acellular bovine pericardium as a bioprosthetic scaffold for tissue engineering. J Mater Sci Mater Med, 2009, 20(11): 2327-2336.
21.	Reing JE, Brown BN, Daly KA, et al. The effects of processing methods upon mechanical and biologic properties of porcine dermal extracellular matrix scaffolds. Biomaterials, 2010, 31(33): 8626-8633.
22.	Brown BN, Freund JM, Han L, et al. Comparison of three methods for the derivation of a biologic scaffold composed of adipose tissue extracellular matrix. Tissue Eng Part C Methods, 2011, 17(4): 411-421.
23.	Rice RD, Ayubi FS, Shaub ZJ, et al. Comparison of Surgisis, AlloDerm, and Vicryl Woven Mesh grafts for abdominal wall defect repair in an animal model. Aesthetic Plast Surg, 2010, 34(3): 290-296.
24.	Ota T, Taketani S, Iwai S, et al. Novel method of decellularization of porcine valves using polyethylene glycol and gamma irradiation. Ann Thorac Surg, 2007, 83(4): 1501-1507.
25.	Mangold S, Schrammel S, Huber G, et al. Evaluation of decellularized human umbilical vein (HUV) for vascular tissue engineering-comparison with endothelium-denuded HUV. J Tissue Eng Regen Med, 2012. [Epub ahead of print].
26.	Schenke-Layland K, Vasilevski O, Opitz F, et al. Impact of decellularization of xenogeneic tissue on extracellular matrix integrity for tissue engineering of heart valves. J Struct Biol, 2003, 143(3): 201-208.
27.	Nam J, Choi SY, Sung SC, et al. Changes of the structural and biomechanical properties of the bovine pericardium after the removal of alpha-Gal epitopes by decellularization and alpha-Galactosidase treatment. Korean J Thorac Cardiovasc Surg, 2012, 45(6): 380-389.
28.	Fishman JM, Ansari T, Sibbons P, et al. Decellularized rabbit cricoarytenoid dorsalis muscle for laryngeal regeneration. Ann Otol Rhinol Laryngol, 2012, 121(2): 129-138.
29.	Gui L, Chan SA, Breuer CK, et al. Novel utilization of serum in tissue decellularization. Tissue Eng Part C Methods, 2010, 16(2): 173-184.
30.	Freytes DO, Stoner RM, Badylak SF. Uniaxial and biaxial properties of terminally sterilized porcine urinary bladder matrix scaffolds. J Biomed Mater Res B Appl Biomater, 2008, 84(2): 408-414.
31.	Kajbafzadeh AM, Javan-Farazmand N, Monajemzadeh M, et al. Determining the optimal decellularization and sterilization protocol for preparing a tissue scaffold of a human-sized liver tissue. Tissue Eng Part C Methods, 2013. [Epub ahead of print].
32.	Russell NA, Rives A, Pelletier MH, et al. The effect of sterilization on the mechanical properties of intact rabbit humeri in three-point bending, four-point bending and torsion. Cell Tissue Bank, 2012. [Epub ahead of print].
33.	Gilbert TW. Strategies for tissue and organ decellularization. J Cell Biochem, 2012, 113(7): 2217-2222.
34.	Uzarski JS, Van De Walle AB, Mcfetridge PS. Preimplantation processing of ex vivo-derived vascular biomaterials: effects on peripheral cell adhesion. J Biomed Mater Res A, 2013, 101(1): 123-131.
35.	Bondioli E, Fini M, Veronesi F, et al. Development and evaluation of a decellularized membrane from human dermis. J Tissue Eng Regen Med, 2012. [Epub ahead of print].
36.	Choi JS, Kim BS, Kim JY, et al. Decellularized extracellular matrix derived from human adipose tissue as a potential scaffold for allograft tissue engineering. J Biomed Mater Res A, 2011, 97(3): 292-299.
37.	Wang JQ, Fan J, Gao JH, et al. Comparison of in vivo adipogenic capabilities of two different extracellular matrix microparticle scaffolds. Plast Reconstr Surg, 2013, 131(2): 174e-187e.
38.	Wolf MT, Daly KA, Reing JE, et al. Biologic scaffold composed of skeletal muscle extracellular matrix. Biomaterials, 2012, 33(10): 2916-2925.
39.	Wang L, Johnson JA, Chang DW, et al. Decellularized musculofascial extracellular matrix for tissue engineering. Biomaterials, 2013, 34(11): 2641-2654.
40.	张晨, 王者生, 高景恒. 软骨脱细胞基质生物性的实验研究. 实用美容整形外科杂志, 2003, 14(2): 59-61.
41.	张晨, 景士兵, 杨琨, 等. 软骨脱细胞基质支架材料的软骨组织工程实验研究. 中国修复重建外科杂志, 2008, 22(7): 846-850.
42.	王寿宇, 吕德成, 张晨, 等. 软骨脱细胞基质的生物力学性质研究. 组织工程与重建外科杂志, 2005, 1(5): 265-267.
43.	Crapo PM, Medberry CJ, Reing JE, et al. Biologic scaffolds composed of central nervous system extracellular matrix. Biomaterials, 2012, 33(13): 3539-3547.
44.	鞠晓军, 郑玲, 柏树令, 等. 人羊膜与人脱细胞羊膜形态结构的对比观察. 现代生物医学进展, 2013, 13(2): 249-252.
45.	鞠晓军, 潘锋, 柏树令, 等. 人脱细胞羊膜复合脂肪源性干细胞修复大鼠全层皮肤缺损的实验研究. 中国修复重建外科杂志, 2010, 24(2): 143-149.
46.	Santi PA, Johnson SB. Decellularized ear tissues as scaffolds for stem cell differentiation. J Assoc Res Otolaryngol, 2013, 14(1): 3-15.
47.	Ma R, Li M, Luo J, et al. Structural integrity, ECM components and immunogenicity of decellularized laryngeal scaffold with preserved cartilage. Biomaterials, 2013, 34(7): 1790-1798.
48.	Totonelli G, Maghsoudlou P, Georgiades F, et al. Detergent enzymatic treatment for the development of a natural acellular matrix for oesophageal regeneration. Pediatr Surg Int, 2013, 29(1): 87-95.

1. Lutolf MP, Hubbell JA. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol, 2005, 23(1): 47-55.
2. Weber B, Emmert MY, Schoenauer R, et al. Tissue engineering on matrix: future of autologous tissue replacement. Semin Immunopathol, 2011, 33(3): 307-315.
3. Flynn LE. The use of decellularized adipose tissue to provide an inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells. Biomaterials, 2010, 31(17): 4715-4724.
4. Francis MP, Sachs PC, Madurantakam PA, et al. Electrospinning adipose tissue-derived extracellular matrix for adipose stem cell culture. J Biomed Mater Res A, 2012, 100(7): 1716-1724.
5. 江燕林, 张忆, 杨洁亮, 等. 脱细胞小牛肌腱组织形态学和生物力学特性研究. 中国修复重建外科杂志, 2013, 27(5): 552-553.
6. Hopkinson A, Shanmuganathan VA, Gray T, et al. Optimization of amniotic membrane (AM) denuding for tissue engineering. Tissue Eng Part C Methods, 2008, 14(4): 371-381.
7. Funamoto S, Nam K, Kimura T, et al. The use of high-hydrostatic pressure treatment to decellularize blood vessels. Biomaterials, 2010, 31(13): 3590-3595.
8. Negishi J, Funamoto S, Kimura T, et al. Porcine radial artery decellularization by high hydrostatic pressure. J Tissue Eng Regen Med, 2012. [Epub ahead of print].
9. Phillips M, Maor E, Rubinsky B. Nonthermal irreversible electroporation for tissue decellularization. J Biomech Eng, 2010, 132(9): 091003.
10. Alhamdani MS, Schroder C, Werner J, et al. Single-step procedure for the isolation of proteins at near-native conditions from mammalian tissue for proteomic analysis on antibody microarrays. J Proteome Res, 2010, 9(2): 963-971.
11. Du L, Wu X, Pang K, et al. Histological evaluation and biomechanical characterisation of an acellular porcine cornea scaffold. Br J Ophthalmol, 2011, 95(3): 410-414.
12. Sicari BM, Johnson SA, Siu BF, et al. The effect of source animal age upon the in vivo remodeling characteristics of an extracellular matrix scaffold. Biomaterials, 2012, 33(22): 5524-5533.
13. Ren H, Shi X, Tao L, et al. Evaluation of two decellularization methods in the development of a whole-organ decellularized rat liver scaffold. Liver Int, 2013, 33(3): 448-458.
14. Sullivan DC, Mirmalek-Sani SH, Deegan DB, et al. Decellularization methods of porcine kidneys for whole organ engineering using a high-throughput system. Biomaterials, 2012, 33(31): 7756-7764.
15. Petersen TH, Calle EA, Zhao L, et al. Tissue-engineered lungs for in vivo implantation. Science, 2010, 329(5991): 538-541.
16. Hudson TW, Liu SY, Schmidt CE. Engineering an improved acellular nerve graft via optimized chemical processing. Tissue Eng, 2004, 10(9-10): 1346-1358.
17. Cebotari S, Tudorache I, Jaekel T, et al. Detergent decellularization of heart valves for tissue engineering: toxicological effects of residual detergents on human endothelial cells. Artif Organs, 2010, 34(3): 206-210.
18. Meyer SR, Chiu B, Churchill TA, et al. Comparison of aortic valve allograft decellularization techniques in the rat. J Biomed Mater Res A, 2006, 79(2): 254-262.
19. Deeken CR, White AK, Bachman SL, et al. Method of preparing a decellularized porcine tendon using tributyl phosphate. J Biomed Mater Res B Appl Biomater, 2011, 96(2): 199-206.
20. Dong X, Wei X, Yi W, et al. RGD-modified acellular bovine pericardium as a bioprosthetic scaffold for tissue engineering. J Mater Sci Mater Med, 2009, 20(11): 2327-2336.
21. Reing JE, Brown BN, Daly KA, et al. The effects of processing methods upon mechanical and biologic properties of porcine dermal extracellular matrix scaffolds. Biomaterials, 2010, 31(33): 8626-8633.
22. Brown BN, Freund JM, Han L, et al. Comparison of three methods for the derivation of a biologic scaffold composed of adipose tissue extracellular matrix. Tissue Eng Part C Methods, 2011, 17(4): 411-421.
23. Rice RD, Ayubi FS, Shaub ZJ, et al. Comparison of Surgisis, AlloDerm, and Vicryl Woven Mesh grafts for abdominal wall defect repair in an animal model. Aesthetic Plast Surg, 2010, 34(3): 290-296.
24. Ota T, Taketani S, Iwai S, et al. Novel method of decellularization of porcine valves using polyethylene glycol and gamma irradiation. Ann Thorac Surg, 2007, 83(4): 1501-1507.
25. Mangold S, Schrammel S, Huber G, et al. Evaluation of decellularized human umbilical vein (HUV) for vascular tissue engineering-comparison with endothelium-denuded HUV. J Tissue Eng Regen Med, 2012. [Epub ahead of print].
26. Schenke-Layland K, Vasilevski O, Opitz F, et al. Impact of decellularization of xenogeneic tissue on extracellular matrix integrity for tissue engineering of heart valves. J Struct Biol, 2003, 143(3): 201-208.
27. Nam J, Choi SY, Sung SC, et al. Changes of the structural and biomechanical properties of the bovine pericardium after the removal of alpha-Gal epitopes by decellularization and alpha-Galactosidase treatment. Korean J Thorac Cardiovasc Surg, 2012, 45(6): 380-389.
28. Fishman JM, Ansari T, Sibbons P, et al. Decellularized rabbit cricoarytenoid dorsalis muscle for laryngeal regeneration. Ann Otol Rhinol Laryngol, 2012, 121(2): 129-138.
29. Gui L, Chan SA, Breuer CK, et al. Novel utilization of serum in tissue decellularization. Tissue Eng Part C Methods, 2010, 16(2): 173-184.
30. Freytes DO, Stoner RM, Badylak SF. Uniaxial and biaxial properties of terminally sterilized porcine urinary bladder matrix scaffolds. J Biomed Mater Res B Appl Biomater, 2008, 84(2): 408-414.
31. Kajbafzadeh AM, Javan-Farazmand N, Monajemzadeh M, et al. Determining the optimal decellularization and sterilization protocol for preparing a tissue scaffold of a human-sized liver tissue. Tissue Eng Part C Methods, 2013. [Epub ahead of print].
32. Russell NA, Rives A, Pelletier MH, et al. The effect of sterilization on the mechanical properties of intact rabbit humeri in three-point bending, four-point bending and torsion. Cell Tissue Bank, 2012. [Epub ahead of print].
33. Gilbert TW. Strategies for tissue and organ decellularization. J Cell Biochem, 2012, 113(7): 2217-2222.
34. Uzarski JS, Van De Walle AB, Mcfetridge PS. Preimplantation processing of ex vivo-derived vascular biomaterials: effects on peripheral cell adhesion. J Biomed Mater Res A, 2013, 101(1): 123-131.
35. Bondioli E, Fini M, Veronesi F, et al. Development and evaluation of a decellularized membrane from human dermis. J Tissue Eng Regen Med, 2012. [Epub ahead of print].
36. Choi JS, Kim BS, Kim JY, et al. Decellularized extracellular matrix derived from human adipose tissue as a potential scaffold for allograft tissue engineering. J Biomed Mater Res A, 2011, 97(3): 292-299.
37. Wang JQ, Fan J, Gao JH, et al. Comparison of in vivo adipogenic capabilities of two different extracellular matrix microparticle scaffolds. Plast Reconstr Surg, 2013, 131(2): 174e-187e.
38. Wolf MT, Daly KA, Reing JE, et al. Biologic scaffold composed of skeletal muscle extracellular matrix. Biomaterials, 2012, 33(10): 2916-2925.
39. Wang L, Johnson JA, Chang DW, et al. Decellularized musculofascial extracellular matrix for tissue engineering. Biomaterials, 2013, 34(11): 2641-2654.
40. 张晨, 王者生, 高景恒. 软骨脱细胞基质生物性的实验研究. 实用美容整形外科杂志, 2003, 14(2): 59-61.
41. 张晨, 景士兵, 杨琨, 等. 软骨脱细胞基质支架材料的软骨组织工程实验研究. 中国修复重建外科杂志, 2008, 22(7): 846-850.
42. 王寿宇, 吕德成, 张晨, 等. 软骨脱细胞基质的生物力学性质研究. 组织工程与重建外科杂志, 2005, 1(5): 265-267.
43. Crapo PM, Medberry CJ, Reing JE, et al. Biologic scaffolds composed of central nervous system extracellular matrix. Biomaterials, 2012, 33(13): 3539-3547.
44. 鞠晓军, 郑玲, 柏树令, 等. 人羊膜与人脱细胞羊膜形态结构的对比观察. 现代生物医学进展, 2013, 13(2): 249-252.
45. 鞠晓军, 潘锋, 柏树令, 等. 人脱细胞羊膜复合脂肪源性干细胞修复大鼠全层皮肤缺损的实验研究. 中国修复重建外科杂志, 2010, 24(2): 143-149.
46. Santi PA, Johnson SB. Decellularized ear tissues as scaffolds for stem cell differentiation. J Assoc Res Otolaryngol, 2013, 14(1): 3-15.
47. Ma R, Li M, Luo J, et al. Structural integrity, ECM components and immunogenicity of decellularized laryngeal scaffold with preserved cartilage. Biomaterials, 2013, 34(7): 1790-1798.
48. Totonelli G, Maghsoudlou P, Georgiades F, et al. Detergent enzymatic treatment for the development of a natural acellular matrix for oesophageal regeneration. Pediatr Surg Int, 2013, 29(1): 87-95.

《中国修复重建外科杂志》

脱细胞技术及其在组织工程中的应用研究进展

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《中国修复重建外科杂志》

脱细胞技术及其在组织工程中的应用研究进展

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