脱细胞生物支架的研究进展
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摘要
在使用脱细胞方法去除组织器官中的细胞成分后,通常仅保留细胞外基质,以此来获得脱细胞生物支架。脱细胞生物支架在组织工程领域有广泛研究,应用于多种组织与器官并取得了良好的效果。脱细胞方法多种多样,在单独使用其中一种方法难以得到好的脱细胞效果时,可将多种方法结合使用以得到较好的脱细胞效果,但也要注意根据不同组织的特点选择合适的脱细胞方法。获得脱细胞支架后可通过组织学染色等方法检测脱细胞效果及生物相容性等情况。
After removing the cellular components in the tissue and organ using the decellularization method,only the extracellular matrix is retained,and thus the decellularized biological scaffold is obtained. Acellular bioscaffolds have been extensively studied in the field of tissue engineering and have been applied to a variety of tissues and organs with good results achieved. When using one method is difficult to obtain a good decellularization effect,a variety of methods can be used in combination to obtain a better effect,and it is also necessary to select the suitable method according to the characteristics of different tissues. After obtaining the acellular scaffold,the decellularization effect and biocompatibility can be detected by histological staining etc.
After removing the cellular components in the tissue and organ using the decellularization method,only the extracellular matrix is retained,and thus the decellularized biological scaffold is obtained. Acellular bioscaffolds have been extensively studied in the field of tissue engineering and have been applied to a variety of tissues and organs with good results achieved. When using one method is difficult to obtain a good decellularization effect,a variety of methods can be used in combination to obtain a better effect,and it is also necessary to select the suitable method according to the characteristics of different tissues. After obtaining the acellular scaffold,the decellularization effect and biocompatibility can be detected by histological staining etc.
引文
[1]冈野光夫,大和雅之.再生医学从书(二)组织工程学[M].沈阳:辽宁科学技术出版社,2016:83-84.
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[3]位晓娟,奚廷斐,郑玉峰.生物源组织工程支架材料研究进展[J].中国修复重建外科杂志,2014,28(6):784-788.
[4] Pashneh-tala S,Macneil S,Claeyssens F. The tissue-engineered vascular graft-past,present,and future[J]. Tissue Eng Part B Rev,2016,22(1):68-100.
[5]孙艳丽,韩宏光,黄带发,等.组织工程心脏瓣膜的构建:现状与前景[J].中国组织工程研究,2013,17(50):8775-8780.
[6] Crapo PM,Gilbert TW,Badylak SF. An overview of tissue and whole organ decellularization processes[J]. Biomaterials,2011,32(12):3233-3243.
[7]鞠成群.脱细胞角膜基质联合内皮样细胞构建生物工程角膜后板层的实验研究[D].济南:山东大学,2012.
[8]霍银平,周利晓,孙成林.脱细胞猪角膜基质支架的制备及其生物相容性[J].中国组织工程研究,2016,20(30):4449-4455.
[9] Guoliu S,Zhu Y. Advances and prospects in tissue-engineered meniscal scaffolds for meniscus regeneration[J]. Stem Cells Int,2015,2015:517520.
[10]苑志国,刘舒云,郝春香,等.脱细胞半月板细胞外基质/脱钙骨基质双相半月板支架的制备及其生物相容性的研究[J].中国医药生物技术,2016,12(1):4-12.
[11]郑幸龙,向俊西,吴万权,等.人肝组织脱细胞支架的制备[J].南方医科大学学报,2015,35(7):1028-1033.
[12] Wang Y,Bao J,Wu X,et al. Genipin crosslinking reduced the immunogenicity of xenogeneic decellularized porcine wholeliver matrices through regulation of immune cell proliferation and polarization[J]. Sci Rep,2016,6:24779.
[13]龚正.灌注法制备肺脱细胞基质[J].中国组织工程研究,2015,19(21):3329-3333.
[14]黑飞龙,周建业,罗富良,等.灌注法大鼠全肺脏脱细胞基质支架的建立[J].北京生物医学工程,2013,32(1):17-21.
[15] Ott HC,Clippinger B,Conrad C,et al. Regeneration and orthotopic transplantation of a bioartificial lung[J]. Nat Med,2010,16(8):927-933.
[16]徐双悦.小口径脱细胞血管支架制备方案的优化、评价及其异种原位移植的初步研究[D].厦门:厦门大学,2017.
[17] Li S,Sengupta D,Chien S. Vascular tissue engineering:from in vitro to in situ[J]. Wiley Interdiscip Rev Syst Biol Med,2013,6(1):61-76.
[18] Wang X,Gu Z,Qin H,et al. Crosslinking effect of dialdehyde starch(DAS)on decellularized porcine aortas for tissue engineering[J]. Int J Biol Macromol,2015,79:813-821.
[19]刘洋.脱细胞脊髓支架制备及其生物相容性的实验研究[D].天津:天津医科大学,2016.
[20] Yousefifard M,Rahimi-movaghar V,Nasirinezhad F,et al. Neural stem/progenitor cell transplantation for spinal cord injury treatment; A systematic review and meta-analysis[J]. Neuroscience,2016,322:377-397.
[21] Kushchayev SV,Giers MB,Hom ED,et al. Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury[J].J Neurosurg Spine,2016,25(1):1-11.
[22]丁明祥,林少华,李亮明,等.骨髓间充质干细胞与脱细胞脑组织支架的生物相容性[J].中国组织工程研究,2013,17(14):2495-2500.
[23]姜涛,张爱君,李雪阳,等.人新型脱细胞真皮制备及性状分析[J].中国组织工程研究,2016,20(7):1006-1012.
[24] Carruthers CA,Dearth CL,Reing JE,et al. Histologic characterization of acellular dermal matrices in a porcine model of tissue expander breast reconstruction[J]. Tissue Eng Part A,2015,21(1/2):35-44.
[25]王心,程宏斌,李媛,等.灌注法制备大鼠全胰腺脱细胞基质支架的实验研究[J].中华普通外科杂志,2016,31(12):1034-1037.
[26]肖原,张杰,陆燕蓉,等.聚氨酯-脱细胞基质复合支架的制备及体内外生物相容性研究[J].中国修复重建外科杂志,2015,29(8):1016-1021.
[27] Keane TJ,Londono R,Turner NJ. Consequences of ineffective decellularization of biologic scaffolds on the host response[J].Biomaterials,2012,33(6):1771-1781.
[28] Keane TJ,Swinehart IT,Badylak SF. Methods of tissue decellularization used for preparation of biologic scaffolds and in vivo relevance[J]. Methods,2015,84:25-34.
[29] Gilbert TW,Sellaro TL,Badylak SF. Decellularization of tissues and organs[J]. Biomaterials,2006,27(19):3675-3683.
[30] Francis MP,Sachs PC,Madurantakam PA,et al. Electrospinning adipose tissue-derived extracellular matrix for adipose stem cell culture[J]. J Biomed Mater Res A,2012,100(7):1716-1724.
[31]彭章松,何云帆,鲁峰.冻融循环及物理匀浆制备高质量脂肪脱细胞基质[J].中国临床解剖学杂志,2018,36(4):392-396.
[32] Yoshihide H,Seiichi F,Shuji S,et al. Preparation and characterization of decellularized cornea using high-hydrostatic pressurization for corneal tissue engineering[J]. Biomaterials,2010,31(14):3941-3948.
[33]周鑫.脱细胞猪角膜基质载体支架的制备及其与人角膜基质细胞的生物相容性研究[D].青岛:中国海洋大学,2013.
[34] Hopkinson A,Shanmuganathan VA,Gray T. Optimization of amniotic membrane(AM)denuding for tissue engineering[J].Tissue Eng Part C Methods,2008,14(4):371-381.
[35] Ju C,Gao YL,Wu X,et al. A human corneal endothelium equivalent constructed with acellular porcine corneal matrix[J].Indian J Med Res,2012,135(6):887-894.
[36] Sawada K,Terada D,Yamaoka T,et al. Cell removal with supercritical carbon dioxide for acellular artificial tissue[J]. J Chem Technol Biotechnol,2008,83(6):943-949.
[37]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[J].中国修复重建外科杂志,2013,27(8):950-954.
[38] Ren H,Shi X,Tao L,et al. Evaluation of two decellularization methods in the development of a whole-organ decellularized rat liver scaffold[J]. Liver Int,2013,33(3):448-458.
[39]邢辉,任先军,蒋涛,等. EDC交联结合化学萃取制备脱细胞脊髓支架及其生物学特性研究[J].中国矫形外科杂志,2016,24(8):732-738.
[40] Uygun BE,Soto-gutierrez A,Yagi H,et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix[J]. Nat Med,2010,16(7):814-820.
[41]姜楠,季茹,王建锋,等.不同方法制备大鼠肝脏脱细胞支架及其免疫原性研究[J].现代生物医学进展,2013,13(5):844-849.
[42] Hudson TW,Liu SY,Schmidt CE. Engineering an improved acellular nerve graft via optimized chemical processing[J]. Tissue Eng,2004,10(9/10):1346-1358.
[43] O'neill JD,Anfang R,Anandappa A. Decellularization of human and porcine lung tissues for pulmonary tissue engineering[J].Ann Thorac Surg,2013,96(3):1046-1055.
[44] Woods T,Gratzer PF. Effectiveness of three extraction techniques in the development of a decellularized bone-anterior cruciate ligament-bone graft[J]. Biomaterials,2005,26(35):7339-7349.
[45]伍权华,陈旭翔,汪蕾,等.心脏脱细胞基质支架的制备及临床应用前景[J].中国组织工程研究,2018,22(6):964-970.
[46] Dahl SL,Koh J,Prabhakar V. Decellularized native and engineered arterial scaffolds for transplantation[J]. Cell Transplant,2003,12(6):659-666.
[47]赵小军,于军,段英飞.骨髓间充质干细胞与膀胱脱细胞基质支架的生物相容性[J].中国组织工程研究,2015,19(36):5769-5773.
[48] Mangold S,Schrammel S,Huber G,et al. Evaluation of decellularized human umbilical vein(HUV)for vascular tissue en gineering-comparison with endothelium-denuded HUV[J].J Tissue Eng Regen Med,2015,9(1):13-23.
[49]钱闯,陈雄生,周盛源,等.牛肌腱冻干脱细胞支架的生物力学特性[J].中国组织工程研究,2015,19(30):4865-4869.
[50]路英进,王秀丽,侯亮,等.心脏脱细胞支架的制备及其生物相容性[J].解剖学杂志,2016,39(2):203-206.
[51] Wang Z,Wang Z,Yu Q,et al. Comparative study of two perfusion routes with different flow in decellularization to harvest an optimal pulmonary scaffold for recellularization[J]. J Biomed Mater Res A,2016,104(10):2567-2575.
[52] Maghsoudlou P,Georgiades F,Tyraskis A,et al. Preservation of micro-architecture and angiogenic potential in a pulmonary acellular matrix obtained using intermittent intra-tracheal flow of detergent enzymatic treatment[J]. Biomaterials,2013,34(28):6638-6648.
[53]刘宾,李菲,张蔓菁,等.超声空化法制备脱细胞血管支架生物学相容性的实验研究[J].中国美容整形外科杂志,2016,27(8):499-502.
[54]赵阳,吴稼晟,周哲,等.人脂肪来源干细胞与膀胱脱细胞基质-丝素蛋白双层支架的生物相容性研究[J].组织工程与重建外科杂志,2014,6:309-313.
[55]蒋丹,黄建文,邵惠丽,等.丝素蛋白/膀胱脱细胞基质/透明质酸复合纤维支架的制备及生物学性能研究[J].功能材料,2017,48(6):6124-6128.
[2] Song JJ,Ott HC. Organ engineering based on decellularized matrix scaffolds[J]. Trends Mol Med,2011,17(8):424-432.
[3]位晓娟,奚廷斐,郑玉峰.生物源组织工程支架材料研究进展[J].中国修复重建外科杂志,2014,28(6):784-788.
[4] Pashneh-tala S,Macneil S,Claeyssens F. The tissue-engineered vascular graft-past,present,and future[J]. Tissue Eng Part B Rev,2016,22(1):68-100.
[5]孙艳丽,韩宏光,黄带发,等.组织工程心脏瓣膜的构建:现状与前景[J].中国组织工程研究,2013,17(50):8775-8780.
[6] Crapo PM,Gilbert TW,Badylak SF. An overview of tissue and whole organ decellularization processes[J]. Biomaterials,2011,32(12):3233-3243.
[7]鞠成群.脱细胞角膜基质联合内皮样细胞构建生物工程角膜后板层的实验研究[D].济南:山东大学,2012.
[8]霍银平,周利晓,孙成林.脱细胞猪角膜基质支架的制备及其生物相容性[J].中国组织工程研究,2016,20(30):4449-4455.
[9] Guoliu S,Zhu Y. Advances and prospects in tissue-engineered meniscal scaffolds for meniscus regeneration[J]. Stem Cells Int,2015,2015:517520.
[10]苑志国,刘舒云,郝春香,等.脱细胞半月板细胞外基质/脱钙骨基质双相半月板支架的制备及其生物相容性的研究[J].中国医药生物技术,2016,12(1):4-12.
[11]郑幸龙,向俊西,吴万权,等.人肝组织脱细胞支架的制备[J].南方医科大学学报,2015,35(7):1028-1033.
[12] Wang Y,Bao J,Wu X,et al. Genipin crosslinking reduced the immunogenicity of xenogeneic decellularized porcine wholeliver matrices through regulation of immune cell proliferation and polarization[J]. Sci Rep,2016,6:24779.
[13]龚正.灌注法制备肺脱细胞基质[J].中国组织工程研究,2015,19(21):3329-3333.
[14]黑飞龙,周建业,罗富良,等.灌注法大鼠全肺脏脱细胞基质支架的建立[J].北京生物医学工程,2013,32(1):17-21.
[15] Ott HC,Clippinger B,Conrad C,et al. Regeneration and orthotopic transplantation of a bioartificial lung[J]. Nat Med,2010,16(8):927-933.
[16]徐双悦.小口径脱细胞血管支架制备方案的优化、评价及其异种原位移植的初步研究[D].厦门:厦门大学,2017.
[17] Li S,Sengupta D,Chien S. Vascular tissue engineering:from in vitro to in situ[J]. Wiley Interdiscip Rev Syst Biol Med,2013,6(1):61-76.
[18] Wang X,Gu Z,Qin H,et al. Crosslinking effect of dialdehyde starch(DAS)on decellularized porcine aortas for tissue engineering[J]. Int J Biol Macromol,2015,79:813-821.
[19]刘洋.脱细胞脊髓支架制备及其生物相容性的实验研究[D].天津:天津医科大学,2016.
[20] Yousefifard M,Rahimi-movaghar V,Nasirinezhad F,et al. Neural stem/progenitor cell transplantation for spinal cord injury treatment; A systematic review and meta-analysis[J]. Neuroscience,2016,322:377-397.
[21] Kushchayev SV,Giers MB,Hom ED,et al. Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury[J].J Neurosurg Spine,2016,25(1):1-11.
[22]丁明祥,林少华,李亮明,等.骨髓间充质干细胞与脱细胞脑组织支架的生物相容性[J].中国组织工程研究,2013,17(14):2495-2500.
[23]姜涛,张爱君,李雪阳,等.人新型脱细胞真皮制备及性状分析[J].中国组织工程研究,2016,20(7):1006-1012.
[24] Carruthers CA,Dearth CL,Reing JE,et al. Histologic characterization of acellular dermal matrices in a porcine model of tissue expander breast reconstruction[J]. Tissue Eng Part A,2015,21(1/2):35-44.
[25]王心,程宏斌,李媛,等.灌注法制备大鼠全胰腺脱细胞基质支架的实验研究[J].中华普通外科杂志,2016,31(12):1034-1037.
[26]肖原,张杰,陆燕蓉,等.聚氨酯-脱细胞基质复合支架的制备及体内外生物相容性研究[J].中国修复重建外科杂志,2015,29(8):1016-1021.
[27] Keane TJ,Londono R,Turner NJ. Consequences of ineffective decellularization of biologic scaffolds on the host response[J].Biomaterials,2012,33(6):1771-1781.
[28] Keane TJ,Swinehart IT,Badylak SF. Methods of tissue decellularization used for preparation of biologic scaffolds and in vivo relevance[J]. Methods,2015,84:25-34.
[29] Gilbert TW,Sellaro TL,Badylak SF. Decellularization of tissues and organs[J]. Biomaterials,2006,27(19):3675-3683.
[30] Francis MP,Sachs PC,Madurantakam PA,et al. Electrospinning adipose tissue-derived extracellular matrix for adipose stem cell culture[J]. J Biomed Mater Res A,2012,100(7):1716-1724.
[31]彭章松,何云帆,鲁峰.冻融循环及物理匀浆制备高质量脂肪脱细胞基质[J].中国临床解剖学杂志,2018,36(4):392-396.
[32] Yoshihide H,Seiichi F,Shuji S,et al. Preparation and characterization of decellularized cornea using high-hydrostatic pressurization for corneal tissue engineering[J]. Biomaterials,2010,31(14):3941-3948.
[33]周鑫.脱细胞猪角膜基质载体支架的制备及其与人角膜基质细胞的生物相容性研究[D].青岛:中国海洋大学,2013.
[34] Hopkinson A,Shanmuganathan VA,Gray T. Optimization of amniotic membrane(AM)denuding for tissue engineering[J].Tissue Eng Part C Methods,2008,14(4):371-381.
[35] Ju C,Gao YL,Wu X,et al. A human corneal endothelium equivalent constructed with acellular porcine corneal matrix[J].Indian J Med Res,2012,135(6):887-894.
[36] Sawada K,Terada D,Yamaoka T,et al. Cell removal with supercritical carbon dioxide for acellular artificial tissue[J]. J Chem Technol Biotechnol,2008,83(6):943-949.
[37]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[J].中国修复重建外科杂志,2013,27(8):950-954.
[38] Ren H,Shi X,Tao L,et al. Evaluation of two decellularization methods in the development of a whole-organ decellularized rat liver scaffold[J]. Liver Int,2013,33(3):448-458.
[39]邢辉,任先军,蒋涛,等. EDC交联结合化学萃取制备脱细胞脊髓支架及其生物学特性研究[J].中国矫形外科杂志,2016,24(8):732-738.
[40] Uygun BE,Soto-gutierrez A,Yagi H,et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix[J]. Nat Med,2010,16(7):814-820.
[41]姜楠,季茹,王建锋,等.不同方法制备大鼠肝脏脱细胞支架及其免疫原性研究[J].现代生物医学进展,2013,13(5):844-849.
[42] Hudson TW,Liu SY,Schmidt CE. Engineering an improved acellular nerve graft via optimized chemical processing[J]. Tissue Eng,2004,10(9/10):1346-1358.
[43] O'neill JD,Anfang R,Anandappa A. Decellularization of human and porcine lung tissues for pulmonary tissue engineering[J].Ann Thorac Surg,2013,96(3):1046-1055.
[44] Woods T,Gratzer PF. Effectiveness of three extraction techniques in the development of a decellularized bone-anterior cruciate ligament-bone graft[J]. Biomaterials,2005,26(35):7339-7349.
[45]伍权华,陈旭翔,汪蕾,等.心脏脱细胞基质支架的制备及临床应用前景[J].中国组织工程研究,2018,22(6):964-970.
[46] Dahl SL,Koh J,Prabhakar V. Decellularized native and engineered arterial scaffolds for transplantation[J]. Cell Transplant,2003,12(6):659-666.
[47]赵小军,于军,段英飞.骨髓间充质干细胞与膀胱脱细胞基质支架的生物相容性[J].中国组织工程研究,2015,19(36):5769-5773.
[48] Mangold S,Schrammel S,Huber G,et al. Evaluation of decellularized human umbilical vein(HUV)for vascular tissue en gineering-comparison with endothelium-denuded HUV[J].J Tissue Eng Regen Med,2015,9(1):13-23.
[49]钱闯,陈雄生,周盛源,等.牛肌腱冻干脱细胞支架的生物力学特性[J].中国组织工程研究,2015,19(30):4865-4869.
[50]路英进,王秀丽,侯亮,等.心脏脱细胞支架的制备及其生物相容性[J].解剖学杂志,2016,39(2):203-206.
[51] Wang Z,Wang Z,Yu Q,et al. Comparative study of two perfusion routes with different flow in decellularization to harvest an optimal pulmonary scaffold for recellularization[J]. J Biomed Mater Res A,2016,104(10):2567-2575.
[52] Maghsoudlou P,Georgiades F,Tyraskis A,et al. Preservation of micro-architecture and angiogenic potential in a pulmonary acellular matrix obtained using intermittent intra-tracheal flow of detergent enzymatic treatment[J]. Biomaterials,2013,34(28):6638-6648.
[53]刘宾,李菲,张蔓菁,等.超声空化法制备脱细胞血管支架生物学相容性的实验研究[J].中国美容整形外科杂志,2016,27(8):499-502.
[54]赵阳,吴稼晟,周哲,等.人脂肪来源干细胞与膀胱脱细胞基质-丝素蛋白双层支架的生物相容性研究[J].组织工程与重建外科杂志,2014,6:309-313.
[55]蒋丹,黄建文,邵惠丽,等.丝素蛋白/膀胱脱细胞基质/透明质酸复合纤维支架的制备及生物学性能研究[J].功能材料,2017,48(6):6124-6128.
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