Biodegradation of injectable silk fibroin hydrogel prevents negative left ventricular remodeling after myocardial infarction.

ABSTRACT

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.