Crosslinking process optimization of collagen sponge

doi:10.3969/j.issn.2095-4344.2015.16.020

Abstract

Abstract:

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.

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：

Key words: Collagen, Carbodiimides, Cross-Linking Reagents

CLC Number:

R318

Wang Heng, Yu Hong-liu, Lu Jin-ting, Zhao Ying. Crosslinking process optimization of collagen sponge[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(16): 2567-2572.

Figures/Tables 3

高，胶原海绵的孔径无明显差异(图3A)。同样的随着交联温度的升高，交联度不断增大，胶原海绵的孔隙率和吸水率有一定幅度的降低(图3B，C)，等到一定的温度(20 ℃左右)，可能交联度达到最大值后，交联温度的提高对胶原蛋白海绵的孔隙率和吸水率影响并不明显。碳化二亚胺交联显著减缓了支架材料的降解，各组交联材料均表现出了较未交联组高的抗降解能力，20 ℃组抗降解能力较5 ℃组明显提高，而 20 ℃组和35 ℃组差异无显著性意义，表现了与孔隙率、吸水率变化相似的趋势(图3D)。总之，交联温度的升高可以增加分子运动速率从而显著提高交联速率，而随着交联的进行，自由氨基和羧基逐渐减少，使得在交联度达到最大值后，交联过程减慢，因此交联温度的进一步升高并未显著提高交联度，因而胶原蛋白海绵的各个性能也随之改变。 2.4 碳化二亚胺交联条件的优化 2.4.1 不同交联工艺胶原蛋白海绵的扫描电镜表征各海绵样品在交联后其微观结构规则而致密，都呈现出多孔的、有序排列的、互穿网络结构，见图4。通过孔径软件统计，海绵的孔径在50-150 μm之间。这种规则的多孔网络结构不仅提升了材料被细胞识别的能力，提高了它的生物相容性，更可以提高材料的抗降解能力[10-11]。从图4可以看出，由于交联剂的交联作用，增加交联剂碳化二亚胺的浓度和交联时间，加强了胶原分子链之间的作用，略微提升了海绵孔径；交联后的胶原海绵显示更为疏松的多孔网络结构，而纯胶原蛋白海绵则结构更致密些。随着交联浓度和交联时间的增加，材料的网络结构发生变化，孔径逐渐变大，多孔蓬松的结构减少，片状结构增加，这种结构可赋予海绵材料良好的吸水和保湿性能，为其作创面修复材料提供了良好的条件。"

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