采用静电纺丝法制备的明胶组织工程支架耐水性和力学性能较差,无法直接作为软骨组织工程支架使用。为改善其物理化学性能,分别采用1-乙基-3-(3-二甲基氨丙基)-碳化二亚胺(EDC)与戊二醛(GA)对明胶电纺膜进行交联,分析对比了两种交联方法对纤维形貌、溶胀比、交联度、力学性能、细胞毒性及降解性能的影响,并考察了不同交联剂浓度对明胶膜物理和化学性能的影响。结果表明,与GA交联相比,采用1.5% EDC交联可以维持明胶膜的表面形貌,交联度可以达到65%,并且无细胞毒性,更有利于其作为骨及软骨组织工程支架的生物学应用。体外降解实验结果表明,采用GA和EDC交联的明胶膜在降解60d时降解率均为70%左右,基本符合软骨的修复要求。
Gelatin tissue engineering scaffold prepared by electrospinning exhibits poor water resistance and mechanical properties,it must be crosslinked in practice.Crosslinking of gelatin electrospun membranes via 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and glutaraldehyde (GA) were conducted,respectively,and the effect of two crosslinking methods on fiber morphology,swelling ratio,crosslinking degree,mechanical properties,cytotoxicity and degradation performance were investigated.The results shown that compared with GA crosslinking,the surface morphology of the gelatin film could be maintained by EDC crosslinking method,the degree of crosslinking could reach 65% when the degradation time of 60d,and there was no cytotoxicity,which was beneficial to biological application.
[1] 卢伟鹏,张兵,郭燕川.明胶静电纺丝的研究进展[J].明胶科学与技术,2013,33(1):8-14.
[2] Migneault I,Dartiguenave C,Bertrand M J,et al.Glutaraldehyde:behavior in aqueous solution,reaction with proteins,and application to enzyme crosslinking[J].Biotechniques,2004,37(5):790-806.
[3] Ulubayram K,Aksu E,Gurhan S I D,et al.Cytotoxicity evaluation of gelatin sponges prepared with different cross-linking agents[J].Journal of Biomaterials Science,Polymer Edition,2002,13(11):1203-1219.
[4] Jayakrishnan A,Jameela S R.Glutaraldehyde as a fixative in bioprostheses and drug delivery matrices[J].Biomaterials,1996,17(5):471-484.
[5] Zhang Y,Zhang Y,Jiang J,et al.Surface derivatization with spacer molecules on glutaraldehyde-activated amino-microplates for covalent immobilization of β-glucosidase[J].Applied Surface Science,2011,257(7):2712-2716.
[6] Jaiswal D,Brown J L.Nanofiber diameter-dependent MAPK activity in osteoblasts[J].Journal of Biomedical Materials Research Part A,2012,100(11):2921-2928.
[7] Bakhsheshi-Rad H R,Hadisi Z,Hamzah E,et al.Drug delivery and cytocompatibility of ciprofloxacin loaded gelatin nanofibers-coated Mg alloy[J].Materials Letters,2017,207:179-182.
[8] 陆伟,俞洁,郭红丽,等.EDC交联的明胶微球支架制备及其生物相容性研究[J].北华大学学报(自然科学版),2014,15(1):49-53.
[9] 封占增.京尼平,戊二醛或EDC/NHS的交联对构建胶原/壳聚糖真皮支架的作用[D].浙江大学,2014.
[10] Jalaja K,James N R.Electrospun gelatin nanofibers:a facile cross-linking approach using oxidized sucrose[J].International Journal of Biological Macromolecules,2015,73:270-278.
[11] Tonda-Turo C,Cipriani E,Gnavi S,et al.Crosslinked gelatin nanofibres:preparation,characterisation and in vitro studies using glial-like cells[J].Materials Science and Engineering:C,2013,33(5):2723-2735.
[12] Bigi A,Cojazzi G,Panzavolta S,et al.Mechanical and thermal properties of gelatin films at different degrees of glutaraldehyde crosslinking[J].Biomaterials,2001,22(8):763-768.
[13] 王迎军,杨春蓉,汪凌云.EDC/NHS交联对胶原物理化学性能的影响[J].华南理工大学学报(自然科学版),2007,35(12):66-70.
[14] Biscarat,Jennifer,et al.Effect of chemical cross-linking on gelatin membrane solubility with a non-toxic and non-volatile agent:terephthalaldehyde[J].International Journal of Biological Macromolecules,2015,74:5-11.
[15] 丁慧芬,滕方君,韩雨亭,等.乙醇浴“一步交联”法制备明胶三维大孔纳米纤维支架[J].口腔医学研究,2015,31(5):437-440.
[16] Mallick S P,Singh B N,Rastogi A,et al.Design and evaluation of chitosan/poly (L-lactide)/pectin based composite scaffolds for cartilage tissue regeneration[J].International Journal of Biological Macromolecules,2018,112:909-920.
[17] Salvatore L,Carofiglio V E,Stufano P,et al.Potential of electrospun poly (3-hydroxybutyrate)/collagen blends for tissue engineering applications[J].Journal of Healthcare Engineering,2018,2018.
基金资助
云南省科技厅基金(国家三类医疗器械植入支架KHC临床研究);云南省大学生创新创业训练项目(PCL/PVA复合人造皮肤的制备及应用基础研究)
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