胶原蛋白作为医用生物材料对缺损组织修复、再生及重建的作用与意义
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摘要
背景:胶原蛋白因具有低免疫原性,良好的生物相容性和生物降解性,在医用生物材料方面得到广泛应用。目的:综述近年来国内外胶原蛋白的来源、生物活性、改性及其在医用生物材料方面的应用进展。方法:通过计算机检索2010至2018年PubMed、Elsevier、Springerlink、中国知网等数据库发表的相关文章,英文检索词为"collagen,crosslinking,immunogenicity,biocompatibility,tissueengineering",中文检索词为"胶原蛋白,交联,免疫原性,生物相容性,组织工程"。结果与结论:胶原蛋白主要从动物肌腱、皮肤、尾巴等组织中提取获得的,具有良好生物相容性、低免疫原性和降解性等特性,但缺乏足够的机械强度。交联改性或与其他生物材料复合使用均可改善胶原蛋白的机械性能。目前,胶原蛋白已被广泛应用于止血剂与创面敷料、生物补片、骨修复材料、药物释放载体及作为组织工程支架等方面;临床使用显示,胶原蛋白对缺损组织的修复、再生及重建有着显著促进作用。
BACKGROUND: Collagen has been widely used as a medical biomaterial due to its low immunogenicity, good biocompatibility and biodegradability.OBJECTIVE: To summarize the sources, bioactivity, modification of collagen and its application as a medical biomaterial in recent years. METHODS: The first author searched related articles in PubMed, Elsevier, Springerlink, and CNKI from 2010 to 2018. The key words were "collagen, crosslinking, immunogenicity, biocompatibility, tissue engineering" in English and Chinese, respectively. RESULTS AND CONCLUSION: Collagen is mainly extracted from animal tendon, skin, tail and other soft tissues.It has low immunogenicity, good biocompatibility and biodegradability, but has insufficient mechanical strength. Crosslinking modification or combination with other biomaterials can both improve the mechanical properties ofcollagen. Nowadays, collagen is widely used as hemostatic and wound dressing, biological repair patches, bone repairing materials, drug release carriers and tissue engineering scaffolds, which has a significant role in the clinical repair, regeneration and reconstruction of tissue defects.
BACKGROUND: Collagen has been widely used as a medical biomaterial due to its low immunogenicity, good biocompatibility and biodegradability.OBJECTIVE: To summarize the sources, bioactivity, modification of collagen and its application as a medical biomaterial in recent years. METHODS: The first author searched related articles in PubMed, Elsevier, Springerlink, and CNKI from 2010 to 2018. The key words were "collagen, crosslinking, immunogenicity, biocompatibility, tissue engineering" in English and Chinese, respectively. RESULTS AND CONCLUSION: Collagen is mainly extracted from animal tendon, skin, tail and other soft tissues.It has low immunogenicity, good biocompatibility and biodegradability, but has insufficient mechanical strength. Crosslinking modification or combination with other biomaterials can both improve the mechanical properties ofcollagen. Nowadays, collagen is widely used as hemostatic and wound dressing, biological repair patches, bone repairing materials, drug release carriers and tissue engineering scaffolds, which has a significant role in the clinical repair, regeneration and reconstruction of tissue defects.
引文
[1]Pawelec KM,Best SM,Cameron RE.Collagen:a network for regenerative medicine.J Mater Chem B Mater Biol Med.2016;4(40):6484-6496.
[2]Sellem PH,Caranzan FR,Bene MC,et al.Immunogenicity of Injectable Collagen Implants.Dermatol Surg.2013;13(11):1199-1203.
[3]Delgado L,Bayon Y,Pandit A,et al.To cross-link or not to cross-link?Cross-linking associated foreign body response of collagen-based devices.Tissue Eng Part B Rev.2015;21(3):298.
[4]Avila RM,Rodriguez BL,Sanchez ML.Collagen:A review on its sources and potential cosmetic applications J Cosmet Dermatol.2018;17(1):20-26.
[5]温慧芳,陈丽丽,白春清,等.基于不同提取方法的鮰鱼皮胶原蛋白理化性质的比较研究[J].食品科学,2016,37(1):74-81.
[6]刘迪,王利强,任莹.猪跟腱胶原蛋白酶法提取工艺的研究[J].食品工业,2017,39(10):72-77.
[7]冯文婕,赵粼,阙斐.酸酶复合法优化鱼鳞胶原蛋白的提取工艺[J].湖北农业科学,2016,55(5):1242-1246.
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[9]He J,Ma X,Zhang F,et al.New strategy for expression of recombinant hydroxylated human collagenα1(III)chains in Pichia pastoris GS115.Biotechnol Appl Biochem.2015;62(3):293-299.
[10]李伟娜,尚子方,段志广,等.毕赤酵母高密度发酵产Ⅲ型类人胶原蛋白及其胃粘膜修复功能[J].生物工程学报,2017,33(4):672-682.
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[12]雷静,李奕恒,刘旭昭,等.动物源Ⅰ型胶原蛋白可引起BALB/c小鼠细胞免疫反应和组织免疫毒性[J].中国组织工程研究,2015,19(34):5506-5512.
[13]王建华,贺超龙,程娘梅,等.无花果蛋白酶去除牛腱Ⅰ型胶原蛋白末端肽的工艺研究[C].第六届全国组织工程与再生医学大会,2013.
[14]Peng YY,Glattauer V,Ramshaw JA,et al.Evaluation of the immunogenicity and cell compatibility of avian collagen for biomedical applications.J Biomed Mater Res Part A.2010;93(4):1235.
[15]李晓辉,倪赛巧,王翀,等.超高压及酶解对虹鳟鱼Ⅰ型胶原蛋白抗原性的影响[EB/OL].http://kns.cnki.net/kcms/detail/11.2206.TS.20180323.1016.088.ht ml.2018-03-23.
[16]宫妍婕,王龙,董来东,等.不同冻存液及降温方式对心脏瓣膜组织学及免疫原性的影响[J].山东大学学报(医学版),2016,54(8):44-49.
[17]李毅,王洪瑾.牛跟腱胶原蛋白提取工艺的生物安全性研究[J].中国美容整形外科杂志,2017,28(10):623-626.
[18]盛嘉隽.重组人胶原纳米纤维支架的制备及其生物相容性检测[D].上海:第二军医大学,2017.
[19]Jab?ońskatrypu?A,Matejczyk M,Rosochacki S.Matrix metalloproteinases(MMPs),the main extracellular matrix(ECM)enzymes in collagen degradation,as a target for anticancer drugs.J Enzyme Inhib Med Chem.2016;23(sup1):177-183.
[20]符锋,秦喆,李晓红,等.胶原/壳聚糖复合支架植入大鼠不同部位降解速率的变化[J].中国组织工程研究,2017,21(6):864-870.
[21]Rahmanian-Schwarz A,Held M,Knoeller T,et al.In vivo biocompatibility and biodegradation of a novel thin and mechanically stable collagen scaffoldJ Biomed Mater Res A.2014;102(4):1173-1179.
[22]Davidenko N,Bax DV,Schuster CF,et al.Optimisation of UVirradiation as a binding site conserving method for crosslinking collagen-based scaffolds.J Mater Sci Mater Med.2016;27(1):14.
[23]Bellincampi LD,Dunn MG.Effect of crosslinking method on collagen fiber‐fibroblast interactions.J Appl Polym Sci.2015;63(11):1493-1498.
[24]张义.不同交联剂对胶原蛋白可食膜性能的影响[D].天津:天津科技大学,2016.
[25]Perez-Puyana V,Romero A,Guerrero A.Influence of collagen concentration and glutaraldehyde on collagen-based scaffold properties.J Biomed Mater Res A.2016;104(6):1462-1468.
[26]Zhou X,Tao Y,Chen E,et al.Genipin-cross-linked type II collagen scaffold promotes the differentiation of adipose-derived stem cells into nucleus pulposus-like cells.J Biomed Mater Res A.2018;106(5):1258-1268.
[27]Gao S,Yuan Z,Guo W,et al.Comparison of glutaraldehyde and carbodiimides to crosslink tissue engineering scaffolds fabricated by decellularized porcine menisci.Mater Sci Eng C.2017;71:891-900.
[28]Cholas R,Kunjalukkal P S,Gervaso F,et al.Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen matrix Mater Sci Eng C.2016,63:499-505.
[29]Baheiraei N,Nourani MR,Mortazavi S,et al.Development of a bioactive porous collagen/beta-tricalcium phosphate bone graft assisting rapid vascularization for bone tissue engineering applications.J Biomed Mater Res A.2018;106(1):73-85.
[30]Long T,Yang J,Shi SS,et al.Fabrication of three-dimensional porous scaffold based on collagen fiber and bioglass for bone tissue engineering.J Biomed Mater Res B Appl Biomater.2015;103(7):1455-1464.
[31]Raftery RM,Woods B,Marques ALP,et al.Multifunctional Biomaterials from the Sea:Assessing the effects of Chitosan incorporation into Collagen Scaffolds on Mechanical and Biological Functionality.Acta Biomaterialia.2016;43:160-169.
[32]鲁瑶.可吸收胶原蛋白止血海绵在腔镜甲状腺手术中的止血疗效[J].中国医药科学,2014,4(17):196-197.
[33]Ramanathan G,Singaravelu S,Muthukumar T,et al.Design and characterization of 3D hybrid collagen matrixes as a dermal substitute in skin tissue engineering Mater Sci Eng C Mater Biol Appl.2017;72:359-370.
[34]雷静,刘旭昭,陈淡嫦,等.凝胶型胶原敷料修复糖尿病皮肤缺损及促进血管再生[J].中国组织工程研究,2014,18(52):8456-8462.
[35]罗心凯,陈治标,陈谦学.免缝胶原海绵人工硬脑膜在颅脑损伤大骨瓣减压术中的应用[J].中国临床神经外科杂志,2016,21(6):357-358.
[36]Du T,Niu X,Li Z,et al.Crosslinking induces high mineralization of apatite minerals on collagen fibers.Int J Biol Macromol.2018;113:450-457.
[37]Shi XD,Chen LW,Li SW,et al.The observed difference of RAW264.7 macrophage phenotype on mineralized collagen and hydroxyapatite.Biomed Mater.2018;13(4):041001.
[38]芶印尧,祝少博.可注射性生物复合材料修复老年膝关节软骨损伤的应用分析[J].实用药物与临床,2017,20(3):280-283.
[39]Wang Y,Hua Y,Zhang Q,et al.Using biomimetically mineralized collagen membranes with different surface stiffness to guide regeneration of bone defects.J Tissue Eng Regen Med.2018;12(7):1545-1555.
[40]Hall BI,Paladino E,Szabo P,et al.Electrospun collagen-based nanofibres:A sustainable material for improved antibiotic utilisation in tissue engineering applicationsInt J Pharm.2017;531(1):67-79.
[41]Chen Y,Kawazoe N,Chen G.Preparation of dexamethasoneloaded biphasic calcium phosphate nanoparticles/collagen porous composite scaffolds for bone tissue engineering.Acta Biomater.2017;67:341-353.
[42]Sun X,Wang J,Wang Y,et al.Collagen-based porous scaffolds containing PLGA microspheres for controlled kartogenin release in cartilage tissue engineering.Artif Cells Nanomed Biotechnol.2017:1-10.
[43]Chan EC,Kuo SM,Kong AM,et al.Three Dimensional Collagen Scaffold Promotes Intrinsic Vascularisation for Tissue Engineering Applications.PLoS One.2016;11(2):e0149799.
[44]Hoogenkamp HR,Pot MW,Hafmans TG,et al.Scaffolds for whole organ tissue engineering:Construction and in vitro evaluation of a seamless,spherical and hollow collagen bladder construct with appendices.Acta Biomater.2016;43:112-121.
[45]Nguyen BB,Moriarty RA,Kamalitdinov T,et al.Collagen hydrogel scaffold promotes mesenchymal stem cell and endothelial cell coculture for bone tissue engineering.J Biomed Mater Res A.2017;105(4):1123-1131.
[46]Lee H,Yang GH,Kim M,et al.Fabrication of micro/nanoporous collagen/dECM/silk-fibroin biocomposite scaffolds using a low temperature 3D printing process for bone tissue regeneration Mater Sci Eng C Mater Biol Appl.2018;84:140-147.
[47]Yang X,Lu Z,Wu H,et al.Collagen-alginate as bioink for three-dimensional(3D)cell printing based cartilage tissue engineering.Mater Sci Eng C Mater Biol Appl.2018;83:195-201.
[48]唐洪,刘俊利,朱长宝,等.碳化二亚胺作为胶原蛋白交联剂的生物安全性评价[J].中华实验外科杂志,2015,32(10):2510-2513.
[49]谢玥,王晨,邱东.戊二醛对成骨细胞毒性的研究[J].明胶科学与技术,2014,34(3):130-135.
[50]Casali DM,Yost MJ,Matthews MA.Eliminating Glutaraldehyde from Crosslinked Collagen Films using Supercritical CO2.JBiomed Mater Res Part A.2017;106(1):86-94.
[51]夏磊磊,毅陈,门福民,等.不同组织来源的胶原蛋白生物材料物理性能对比研究[J].材料科学,2017,7(4):431-439.
[52]阮功成,曹慧,徐斐,等.不同来源胶原蛋白抗冻活性的研究[J].食品科学,2014,35(17):22-26.
[53]Drzewiecki KE,Malavade JN,Ahmed I,et al.A thermoreversible,photocrosslinkable collagen bio-ink for free-form fabrication of scaffolds for regenerative medicine Technology(Singap World Sci).2017;5(4):185-195.
[2]Sellem PH,Caranzan FR,Bene MC,et al.Immunogenicity of Injectable Collagen Implants.Dermatol Surg.2013;13(11):1199-1203.
[3]Delgado L,Bayon Y,Pandit A,et al.To cross-link or not to cross-link?Cross-linking associated foreign body response of collagen-based devices.Tissue Eng Part B Rev.2015;21(3):298.
[4]Avila RM,Rodriguez BL,Sanchez ML.Collagen:A review on its sources and potential cosmetic applications J Cosmet Dermatol.2018;17(1):20-26.
[5]温慧芳,陈丽丽,白春清,等.基于不同提取方法的鮰鱼皮胶原蛋白理化性质的比较研究[J].食品科学,2016,37(1):74-81.
[6]刘迪,王利强,任莹.猪跟腱胶原蛋白酶法提取工艺的研究[J].食品工业,2017,39(10):72-77.
[7]冯文婕,赵粼,阙斐.酸酶复合法优化鱼鳞胶原蛋白的提取工艺[J].湖北农业科学,2016,55(5):1242-1246.
[8]黄雯.鮰鱼鱼皮和鲅鱼鱼皮胶原蛋白的提取与性质研究[D].上海:上海海洋大学,2015.
[9]He J,Ma X,Zhang F,et al.New strategy for expression of recombinant hydroxylated human collagenα1(III)chains in Pichia pastoris GS115.Biotechnol Appl Biochem.2015;62(3):293-299.
[10]李伟娜,尚子方,段志广,等.毕赤酵母高密度发酵产Ⅲ型类人胶原蛋白及其胃粘膜修复功能[J].生物工程学报,2017,33(4):672-682.
[11]Kumar VA,Taylor NL,Jalan AA,et al.A nanostructured synthetic collagen mimic for hemostasis.Biomacromolecules.2014;15(4):1484-1490.
[12]雷静,李奕恒,刘旭昭,等.动物源Ⅰ型胶原蛋白可引起BALB/c小鼠细胞免疫反应和组织免疫毒性[J].中国组织工程研究,2015,19(34):5506-5512.
[13]王建华,贺超龙,程娘梅,等.无花果蛋白酶去除牛腱Ⅰ型胶原蛋白末端肽的工艺研究[C].第六届全国组织工程与再生医学大会,2013.
[14]Peng YY,Glattauer V,Ramshaw JA,et al.Evaluation of the immunogenicity and cell compatibility of avian collagen for biomedical applications.J Biomed Mater Res Part A.2010;93(4):1235.
[15]李晓辉,倪赛巧,王翀,等.超高压及酶解对虹鳟鱼Ⅰ型胶原蛋白抗原性的影响[EB/OL].http://kns.cnki.net/kcms/detail/11.2206.TS.20180323.1016.088.ht ml.2018-03-23.
[16]宫妍婕,王龙,董来东,等.不同冻存液及降温方式对心脏瓣膜组织学及免疫原性的影响[J].山东大学学报(医学版),2016,54(8):44-49.
[17]李毅,王洪瑾.牛跟腱胶原蛋白提取工艺的生物安全性研究[J].中国美容整形外科杂志,2017,28(10):623-626.
[18]盛嘉隽.重组人胶原纳米纤维支架的制备及其生物相容性检测[D].上海:第二军医大学,2017.
[19]Jab?ońskatrypu?A,Matejczyk M,Rosochacki S.Matrix metalloproteinases(MMPs),the main extracellular matrix(ECM)enzymes in collagen degradation,as a target for anticancer drugs.J Enzyme Inhib Med Chem.2016;23(sup1):177-183.
[20]符锋,秦喆,李晓红,等.胶原/壳聚糖复合支架植入大鼠不同部位降解速率的变化[J].中国组织工程研究,2017,21(6):864-870.
[21]Rahmanian-Schwarz A,Held M,Knoeller T,et al.In vivo biocompatibility and biodegradation of a novel thin and mechanically stable collagen scaffoldJ Biomed Mater Res A.2014;102(4):1173-1179.
[22]Davidenko N,Bax DV,Schuster CF,et al.Optimisation of UVirradiation as a binding site conserving method for crosslinking collagen-based scaffolds.J Mater Sci Mater Med.2016;27(1):14.
[23]Bellincampi LD,Dunn MG.Effect of crosslinking method on collagen fiber‐fibroblast interactions.J Appl Polym Sci.2015;63(11):1493-1498.
[24]张义.不同交联剂对胶原蛋白可食膜性能的影响[D].天津:天津科技大学,2016.
[25]Perez-Puyana V,Romero A,Guerrero A.Influence of collagen concentration and glutaraldehyde on collagen-based scaffold properties.J Biomed Mater Res A.2016;104(6):1462-1468.
[26]Zhou X,Tao Y,Chen E,et al.Genipin-cross-linked type II collagen scaffold promotes the differentiation of adipose-derived stem cells into nucleus pulposus-like cells.J Biomed Mater Res A.2018;106(5):1258-1268.
[27]Gao S,Yuan Z,Guo W,et al.Comparison of glutaraldehyde and carbodiimides to crosslink tissue engineering scaffolds fabricated by decellularized porcine menisci.Mater Sci Eng C.2017;71:891-900.
[28]Cholas R,Kunjalukkal P S,Gervaso F,et al.Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen matrix Mater Sci Eng C.2016,63:499-505.
[29]Baheiraei N,Nourani MR,Mortazavi S,et al.Development of a bioactive porous collagen/beta-tricalcium phosphate bone graft assisting rapid vascularization for bone tissue engineering applications.J Biomed Mater Res A.2018;106(1):73-85.
[30]Long T,Yang J,Shi SS,et al.Fabrication of three-dimensional porous scaffold based on collagen fiber and bioglass for bone tissue engineering.J Biomed Mater Res B Appl Biomater.2015;103(7):1455-1464.
[31]Raftery RM,Woods B,Marques ALP,et al.Multifunctional Biomaterials from the Sea:Assessing the effects of Chitosan incorporation into Collagen Scaffolds on Mechanical and Biological Functionality.Acta Biomaterialia.2016;43:160-169.
[32]鲁瑶.可吸收胶原蛋白止血海绵在腔镜甲状腺手术中的止血疗效[J].中国医药科学,2014,4(17):196-197.
[33]Ramanathan G,Singaravelu S,Muthukumar T,et al.Design and characterization of 3D hybrid collagen matrixes as a dermal substitute in skin tissue engineering Mater Sci Eng C Mater Biol Appl.2017;72:359-370.
[34]雷静,刘旭昭,陈淡嫦,等.凝胶型胶原敷料修复糖尿病皮肤缺损及促进血管再生[J].中国组织工程研究,2014,18(52):8456-8462.
[35]罗心凯,陈治标,陈谦学.免缝胶原海绵人工硬脑膜在颅脑损伤大骨瓣减压术中的应用[J].中国临床神经外科杂志,2016,21(6):357-358.
[36]Du T,Niu X,Li Z,et al.Crosslinking induces high mineralization of apatite minerals on collagen fibers.Int J Biol Macromol.2018;113:450-457.
[37]Shi XD,Chen LW,Li SW,et al.The observed difference of RAW264.7 macrophage phenotype on mineralized collagen and hydroxyapatite.Biomed Mater.2018;13(4):041001.
[38]芶印尧,祝少博.可注射性生物复合材料修复老年膝关节软骨损伤的应用分析[J].实用药物与临床,2017,20(3):280-283.
[39]Wang Y,Hua Y,Zhang Q,et al.Using biomimetically mineralized collagen membranes with different surface stiffness to guide regeneration of bone defects.J Tissue Eng Regen Med.2018;12(7):1545-1555.
[40]Hall BI,Paladino E,Szabo P,et al.Electrospun collagen-based nanofibres:A sustainable material for improved antibiotic utilisation in tissue engineering applicationsInt J Pharm.2017;531(1):67-79.
[41]Chen Y,Kawazoe N,Chen G.Preparation of dexamethasoneloaded biphasic calcium phosphate nanoparticles/collagen porous composite scaffolds for bone tissue engineering.Acta Biomater.2017;67:341-353.
[42]Sun X,Wang J,Wang Y,et al.Collagen-based porous scaffolds containing PLGA microspheres for controlled kartogenin release in cartilage tissue engineering.Artif Cells Nanomed Biotechnol.2017:1-10.
[43]Chan EC,Kuo SM,Kong AM,et al.Three Dimensional Collagen Scaffold Promotes Intrinsic Vascularisation for Tissue Engineering Applications.PLoS One.2016;11(2):e0149799.
[44]Hoogenkamp HR,Pot MW,Hafmans TG,et al.Scaffolds for whole organ tissue engineering:Construction and in vitro evaluation of a seamless,spherical and hollow collagen bladder construct with appendices.Acta Biomater.2016;43:112-121.
[45]Nguyen BB,Moriarty RA,Kamalitdinov T,et al.Collagen hydrogel scaffold promotes mesenchymal stem cell and endothelial cell coculture for bone tissue engineering.J Biomed Mater Res A.2017;105(4):1123-1131.
[46]Lee H,Yang GH,Kim M,et al.Fabrication of micro/nanoporous collagen/dECM/silk-fibroin biocomposite scaffolds using a low temperature 3D printing process for bone tissue regeneration Mater Sci Eng C Mater Biol Appl.2018;84:140-147.
[47]Yang X,Lu Z,Wu H,et al.Collagen-alginate as bioink for three-dimensional(3D)cell printing based cartilage tissue engineering.Mater Sci Eng C Mater Biol Appl.2018;83:195-201.
[48]唐洪,刘俊利,朱长宝,等.碳化二亚胺作为胶原蛋白交联剂的生物安全性评价[J].中华实验外科杂志,2015,32(10):2510-2513.
[49]谢玥,王晨,邱东.戊二醛对成骨细胞毒性的研究[J].明胶科学与技术,2014,34(3):130-135.
[50]Casali DM,Yost MJ,Matthews MA.Eliminating Glutaraldehyde from Crosslinked Collagen Films using Supercritical CO2.JBiomed Mater Res Part A.2017;106(1):86-94.
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