Department of Biomedical Engineering, National Cerebral and Cardiovascular Center (NCVC) Research Institute, 6-1 Kishibeshinmachi, Suita, Osaka 564-8565, Japan.
Biomater Sci. 2019 Sep 24;7(10):4153-4165. doi: 10.1039/c9bm00556k.
In the present study, we investigated the optimal material properties of a tunable hydrogel for the treatment of myocardial infarction (MI) along with the therapeutic mechanism. We developed silk fibroin (SF) hydrogels with the same physical properties (e.g., stiffness) but different biodegradation rates via a peptide modification and evaluated the effect of hydrogel biodegradation on the prevention of negative left ventricular (LV) remodeling in a rat model of MI. LV enlargement was attenuated to a greater extent by injection of a slowly degrading unmodified SF hydrogel as compared to a rapidly degrading peptide-modified SF (SF + Pep) hydrogel for up to 12 weeks post-injection. This could not be explained by the mechanical stabilization of the LV wall by the injectant since the SF and SF + Pep hydrogels degraded completely within 4 weeks and the two groups showed no difference in LV wall thickness at 12 weeks. The SF group had dense randomly aligned collagen fibers whereas the SF + Pep group had sparse fibers surrounding the LV. These results suggest that randomly aligned fibrous tissues formed during/after biodegradation of a slowly degrading SF hydrogel may be more resistant to LV pressure and thus prevent LV enlargement.
在本研究中，我们研究了一种可调谐水凝胶的最佳材料特性，用于治疗心肌梗死（MI）以及治疗机制。我们通过肽修饰开发了具有相同物理性质（例如，硬度）但降解率不同的丝素蛋白（SF）水凝胶，并评估了水凝胶降解对预防 MI 大鼠模型中左心室（LV）重构的负面影响。与快速降解的肽修饰 SF（SF + Pep）水凝胶相比，注射缓慢降解的未修饰 SF 水凝胶在注射后长达 12 周时，LV 扩张程度得到了更大程度的抑制。这不能用注入物对 LV 壁的机械稳定来解释，因为 SF 和 SF + Pep 水凝胶在 4 周内完全降解，两组在 12 周时 LV 壁厚度没有差异。SF 组有密集的随机排列的胶原纤维，而 SF + Pep 组则有稀疏的纤维环绕 LV。这些结果表明，在缓慢降解的 SF 水凝胶的生物降解过程中/之后形成的随机排列的纤维组织可能对 LV 压力更具抵抗力，从而防止 LV 扩张。
