Department of Anesthesiology and the Vascular Biology and Therapeutics Program, Yale University, New Haven, Connecticut, USA.
Tissue Eng Part A. 2011 May;17(9-10):1191-200. doi: 10.1089/ten.TEA.2010.0508. Epub 2011 Jan 16.
Functional connective tissues have been developed using tissue engineering approach by seeding cells on biodegradable scaffolds such as polyglycolic acid (PGA). However, a major drawback of tissue engineering approaches that utilize synthetic polymers is the persistence of polymer remnants in engineered tissues at the end of culture. Such polymer fragments may significantly degrade tissue mechanics and stimulate local inflammatory responses in vivo. In this study, several polymeric materials with a range of degradation profiles were developed and evaluated for their potential applications in construction of collagen matrix-rich tissues, particularly tissue-engineered blood vessels. The degradation characteristics of these polymers were compared as were their characteristics vis-à-vis cell adhesion and proliferation, collagen synthesis, and ability to support growth of engineered vessels. Under aqueous conditions at 37°C, Polymer I (comprising 84% glycolide and 16% trimethylene carbonate [TMC]) had a similar degradation profile to PGA, Polymer II (comprising 84% glycolide, 14% TMC, and 2% polyethylene succinate) degradedly more slowly, but Polymer III (comprising 87% glycolide, 7% TMC, and 6% polyethylene glycol) had a more extensive degradation as compared to PGA. All polymers supported cell proliferation, but Polymer III improved collagen production and engineered vessel mechanics as compared with PGA. In addition, more slowly degrading polymers were associated with poorer final vessel mechanics. These results suggest that polymers that degrade more quickly during tissue culture actually result in improved engineered tissue mechanics, by virtue of decreased disruption of collagenous extracellular matrix.
功能性连接组织已通过在生物可降解支架(如聚乙醇酸(PGA))上接种细胞的组织工程方法开发。然而,利用合成聚合物的组织工程方法的一个主要缺点是,在培养结束时,工程组织中仍然存在聚合物残留物。这些聚合物片段可能会显著降低组织力学性能,并在体内刺激局部炎症反应。在这项研究中,开发了几种具有不同降解特性的聚合物材料,并评估了它们在构建富含胶原蛋白基质的组织,特别是组织工程血管中的潜在应用。比较了这些聚合物的降解特性及其与细胞黏附、增殖、胶原蛋白合成和支持工程血管生长的能力有关的特性。在 37°C 的水介质中,聚合物 I(包含 84%的乙交酯和 16%的三亚甲基碳酸酯[TMC])的降解特性与 PGA 相似,聚合物 II(包含 84%的乙交酯、14%的 TMC 和 2%的聚己二酸丁二醇酯)降解速度较慢,但聚合物 III(包含 87%的乙交酯、7%的 TMC 和 6%的聚乙二醇)的降解速度比 PGA 快。所有聚合物都支持细胞增殖,但聚合物 III 比 PGA 提高了胶原蛋白的产生和工程血管的力学性能。此外,降解速度较慢的聚合物与最终血管力学性能较差有关。这些结果表明,在组织培养过程中降解更快的聚合物实际上通过减少对胶原蛋白细胞外基质的破坏,导致改善了工程组织的力学性能。