Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, CPZN 4809, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
J Biomed Mater Res A. 2009 Dec 15;91(4):1038-47. doi: 10.1002/jbm.a.32327.
Poly(glycerol sebacate) (PGS), a promising scaffold material for soft tissue engineering applications, is a soft, tough elastomer with excellent biocompatibility. However, the rapid in vivo degradation rate of PGS limits its use as a scaffold material. To determine the impact of crosslink density on degradation rate, a family of PGS materials was synthesized by incrementally increasing the curing time from 42 to 144 h, at 120 degrees C and 10 mTorr vacuum. As expected, PGS became a stiffer, tougher, and stronger elastomer with increasing curing time. PGS disks were subcutaneously implanted into rats and periodically harvested; only mild tissue responses were observed and the biocompatibility remained excellent. Regardless of crosslink density, surface erosion degradation was observed. The sample dimensions linearly decreased with implantation time, and the mass loss rates were constant after 1-week implantation. As surface erosion degradation frequently correlates with enzymatic digestion, parallel in vitro digestion studies were conducted in lipase solutions which hydrolyze ester bonds. Enzymatic digestion played a significant role in degrading PGS, and the mass loss rates were not a function of curing time. Alternative chemistry approaches will be required to decrease the enzymatic hydrolysis rate of the ester bonds in PGS polymers.
聚(癸二酸丙二醇酯)(PGS)是一种很有前途的软组织工程应用支架材料,它是一种柔软、坚韧的弹性体,具有极好的生物相容性。然而,PGS 的体内快速降解率限制了其作为支架材料的应用。为了确定交联密度对降解速率的影响,通过在 120°C 和 10 mTorr 真空下逐步增加固化时间(从 42 小时增加到 144 小时),合成了一系列 PGS 材料。正如预期的那样,随着固化时间的增加,PGS 成为一种更硬、更坚韧和更强的弹性体。将 PGS 圆盘皮下植入大鼠体内并定期取出;仅观察到轻微的组织反应,生物相容性仍然很好。无论交联密度如何,都观察到表面侵蚀降解。样品尺寸随植入时间线性减小,植入 1 周后质量损失率保持恒定。由于表面侵蚀降解通常与酶消化有关,因此在脂肪酶溶液中进行了平行的体外消化研究,脂肪酶可以水解酯键。酶消化在降解 PGS 方面起着重要作用,质量损失率与固化时间无关。需要采用替代化学方法来降低 PGS 聚合物中酯键的酶水解速率。