Kim Seon Ae, Go Eun Jeong, Bae Bo Seung, Jung Jae Woong, Cho Mi-La, Shetty Asode Ananthram, Kim Seok Jung
Department of Orthopedic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, 02453 Seoul, Republic of Korea.
Regen Ther. 2025 Mar 29;29:292-302. doi: 10.1016/j.reth.2025.03.015. eCollection 2025 Jun.
Collagen-based materials differ in absorption time, biodegradation patterns, and inflammatory cell infiltration. This study aimed to evaluate the biocompatibility and biodegradation of native, differently processed, and cross-linked porcine collagen membranes implanted in the subcutaneous tissue of rats, following ISO 10993-6:2016.
Sixty Sprague-Dawley rats were randomly divided into four groups: Group 1 (lyophilized 3 % porcine type I collagen membrane), Group 2 (lyophilized 3 % porcine type I collagen membrane, dehydrothermal [DHT]), Group 3 (1,4-butanediol diglycidyl ether [BDDE] cross-linked, lyophilized 3 % porcine type I collagen), and Group 4 (BDDE cross-linked, lyophilized 3 % porcine type I collagen, DHT). The experimental periods were 1, 2, 4, 8, and 12 weeks, with three animals per group per period. After each period, specimens were extracted and analyzed for membrane structure, biodegradation, cell infiltration, angiogenesis, tissue integration, and foreign body reaction using histological staining and scoring according to ISO 10993-6:2016.
The cross-linked collagen membrane groups maintained their porous structure, with cell infiltration and blood vessel formation observed within this structure. Non-cross-linked collagen membranes (Group 1) appeared as lumps under the subcutaneous tissue and exhibited minimal or no response throughout the observation periods. Groups 2 and 4 biodegraded the fastest. Group 2 membranes were not detected in the subcutaneous tissue at 8 weeks, classified as a slight response. Cross-linked collagen membranes in all groups showed a slight response, whereas Group 4 exhibited a moderate response (11.0-16.9) only at 12 weeks. The tissue response to collagen membranes in all groups aligned with physiological inflammatory processes, scoring from minimal or no response (0.0-5.9) to slight response (6.0-10.9), confirming their biocompatibility.
Cross-linking methods, temperature, and chemical reagents influence collagen membrane properties. Cross-linked collagen formed a porous structure, and high-temperature DHT cross-linking accelerated the biodegradation of the collagen membrane.
基于胶原蛋白的材料在吸收时间、生物降解模式和炎性细胞浸润方面存在差异。本研究旨在按照ISO 10993-6:2016标准，评估植入大鼠皮下组织的天然、不同处理方式以及交联猪胶原蛋白膜的生物相容性和生物降解性。
将60只Sprague-Dawley大鼠随机分为四组：第1组（冻干3%猪I型胶原蛋白膜），第2组（冻干3%猪I型胶原蛋白膜，脱氢热交联[DHT]），第3组（1,4-丁二醇二缩水甘油醚[BDDE]交联的冻干3%猪I型胶原蛋白），第4组（BDDE交联的冻干3%猪I型胶原蛋白，DHT）。实验周期为1、2、4、8和12周，每个周期每组有三只动物。每个周期结束后，取出标本，按照ISO 10993-6:2016标准，使用组织学染色和评分方法分析膜结构、生物降解、细胞浸润、血管生成、组织整合和异物反应。
交联胶原蛋白膜组保持其多孔结构，在该结构内观察到细胞浸润和血管形成。未交联的胶原蛋白膜（第1组）在皮下组织下呈现为块状，在整个观察期内表现出最小或无反应。第2组和第4组生物降解最快。第2组的膜在8周时在皮下组织中未检测到，分类为轻微反应。所有组的交联胶原蛋白膜均显示轻微反应，而第4组仅在12周时表现出中度反应（11.0 - 16.9）。所有组对胶原蛋白膜的组织反应与生理炎症过程一致，评分从最小或无反应（0.0 - 5.9）到轻微反应（6.0 - 10.9），证实了它们的生物相容性。
交联方法、温度和化学试剂会影响胶原蛋白膜的性能。交联胶原蛋白形成多孔结构，高温DHT交联加速了胶原蛋白膜的生物降解。
