Encapsulating chondrocytes in copolymer gels: Bimodal degradation kinetics influence cell phenotype and extracellular matrix development
Encapsulating chondrocytes in copolymer gels: Bimodal degradation kinetics influence cell phenotype and extracellular matrix development
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DOI：
10.1002/jbm.a.30106
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发表时间：
2004-09-15
影响因子：
4.9
通讯作者：
Anseth, KS
中科院分区：
文献类型：
--
作者：
Rice, MA;Anseth, KS
水凝胶为封装软骨细胞和促进软骨组织的产生提供了理想的环境。然而，细胞外基质（ECM）的沉积和最终的组织功能受到凝胶支架降解的显着影响。假设双峰降解过程将捕获新组织发育所需的关键特征。具体来说，大多数初始交联将快速降解并实现 ECM 沉积，而临界量将保留或降解得更慢，以在较长时间内提供结构完整性。在本研究中，软骨细胞被封装在不可降解的[聚(乙二醇)二甲基丙烯酸酯]和可降解的[聚(乳酸)-b-聚(乙二醇)-b-聚(乳酸)二甲基丙烯酸酯]大分子单体的共聚物凝胶中，以研究凝胶降解对ECM进化的影响。所有凝胶均由 10 wt% 总大分子单体溶液合成，其中包含 0、19、21、23、25 或 100 mol% 不可降解单元。 8 周后，发现共聚物构建体的 DNA 含量低于完全可降解的构建体。然而，各种共聚物构建体之间的总生化含量非常相似。组织学分析提供了更有趣的见解，显示共聚物样品中 ECM 成分的空间分布比具有 100 mol% 不可降解单元的构建体更均匀。此外，具有 0 mol% 不可降解单元的构建体中存在许多主要结构缺陷，随着不可降解单元数量的增加，这些缺陷变得不那么明显。总体而言，共聚物凝胶在新组织发育过程中具有较高的压缩模量，并且也没有显示软骨细胞去分化的证据。凭借其双峰降解特性，具有精心选择的降解交联与慢速或非降解交联比例的共聚物凝胶为组织工程软骨中的 ECM 开发提供了明显的优势。 (C) 2004 年 Wiley 期刊公司。
Hydrogels provide an ideal environment for encapsulating chondrocytes and facilitating the production of cartilaginous tissue. However, the deposition of extracellular matrix (ECM) and ultimate tissue function are significantly affected by degradation of gel scaffolds. It was hypothesized that a bimodal degradation process would capture the critical features necessary for neotissue development. Specifically, most of the initial crosslinks would degrade quickly and enable ECM deposition, whereas a critical amount would remain or degrade much more slowly to provide structural integrity over a longer time period. In this study, chondrocytes were encapsulated in copolymer gels of nondegradable [poly(ethylene glycol) dimethacrylate] and degradable [poly(lactic acid)-b-poly(ethylene glycol)-b-poly(lactic acid) dimethacrylate] macromers to investigate the effects of gel degradation on ECM evolution. All gels were synthesized from 10 wt % total macromer solutions consisting of 0, 19, 21, 23, 25, or 100 mol % nondegradable units. The copolymer constructs were found to have lower DNA content than completely degradable constructs after 8 weeks. However, total biochemical content was very similar among the various copolymer constructs. Histological analysis gave more interesting insight, showing a more uniform spatial distribution of ECM components in copolymer samples than in constructs with 100 mol % nondegradable units. In addition, a number of major structural defects were present in constructs with 0 mol % nondegradable units that became less apparent as the amount of nondegradable units was increased. Overall, the copolymer gels had a higher compressive modulus during neotissue development and also showed no evidence of chondrocyte dedifferentiation. With their bimodal degradation profile, copolymer gels with carefully selected ratios of degrading to slow or nondegrading crosslinks provide distinct advantages for ECM development in tissue-engineered cartilage. (C) 2004 Wiley Periodicals, Inc.