胶原蛋白海绵交联工艺的优化

背景：胶原蛋白材料具有良好的生物相容性和生物可降解性，但在临床应用过程中也暴露出了机械强度低、耐降解性能差等问题。大量研究报道，通过适当的交联可以改善胶原蛋白材料的缺陷，调控其多孔网络结构、溶胀性和降解性。目的：优化胶原蛋白海绵的碳化二亚胺交联工艺，探讨其最佳工艺条件。方法：利用碳化二亚胺对胶原蛋白海绵进行交联改性，得到具有疏松、多孔网络结构的胶原蛋白海绵，同时采用正交实验对交联工艺进行优化，单因素中选择碳化二亚胺浓度(5，10，20，30，40，50，60，70，80，90，100 mmol/L)、交联时间(2，4，6，8，12，16，20，24 h)及交联温度(5，10，15，20，25，30，35 ℃)为实验因子，以孔径、孔隙率、吸水性、降解率来筛选胶原蛋白海绵交联的最佳工艺。结果与结论：当碳化二亚胺浓度为50 mmol/L、交联温度为20 ℃、交联时间为6 h时，胶原蛋白海绵的各项性能最为优越，为最优工艺条件，其中平均孔径大小为105 μm，孔隙率为79.45%，吸水率为287.14%，降解率最优为15.04%(2 d)。表明通过对胶原蛋白海绵的交联改性，极大提高了海绵的吸水性能和耐降解性能。中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程全文链接：

Crosslinking process optimization of collagen sponge

BACKGROUND: Collagen materials have good biocompatibility and biodegradability, but also had some problems such as low mechanical strength, poor resistance to degradation exposed in the process of clinical application. Numerous studies have reported that proper crosslinking could improve the disadvantage of collagen materials, regulate porous network structure, swelling and degradation of collagen materials.  OBJECTIVE: To optimize carbodiimide crosslinking process of collagen sponge and determine the best process conditions.METHODS: Collagen sponge was cross-linked by carbodiimide for the preparation of loose and porous collagen sponge. Meanwhile, we optimized the conditions of cross-linking, in which the selected concentration of carbodiimide was 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 mmol/L, linking time was 2, 4, 6, 8, 12, 16, 20, 24 hours, and linking temperature was 5, 10, 15, 20, 25, 30, 35 ℃. We evaluated the best process conditions of collagen sponge through the aperture, porosity, water absorption, and degradation rate.RESULTS AND CONCLUSION: The optimal conditions were carbodiimide concentration 50 mmol/L, crosslinking temperature 20 ℃, crosslinking time 6 hours. At this point, the average pore diameter of collagen sponge was 105 μm, the porosity was 79.45%, water absorption was 287.14%, and the degradation rate was 15.04% (2 days). The crosslinking of collagen sponge significantly improved its water absorption and degradation resistance.