Modulation of material properties of a decellularized myocardial matrix scaffold

Abstract

Injectable materials offer the potential for minimally invasive therapy for myocardial infarction (MI), either as an acellular scaffold or as a cell delivery vehicle. A recently developed myocardial matrix hydrogel, derived from decellularized porcine ventricular tissue, has the potential to aid in cardiac repair following an MI. Herein, we set out to study the effects of cross-linking on the cardiac hydrogel stiffness, degradation properties, cellular migration, and catheter injectability in vitro. Cross-linking increased stiffness, while slowing degradation and cellular migration through the gels. Additionally, the cross-linked material was pushed through a clinically relevant catheter. These results demonstrate that the material properties of myocardial matrix can be tuned via cross-linking, while maintaining appropriate viscosity for catheter injectability.

Figure 1

Rheological effects of crosslinking. Plot of rheological data of GA crosslinked myocardial matrix gels at 0%, 0.05%, and 0.1% GA. Increasing concentrations of GA, increases storage modulus (G′).

Figure 2

Catheter injectability. Despite incorporation of 0.1 % GA, the crosslinked myocardial matrix was capable of being injected through the nitinol tubing of the 27 G Myostar catheter.

Figure 3

Myocardial matrix degradation in vitro. Degradation of uncrosslinked and crosslinked gels at 5 and 24 hours of incubation with collagenase. Increasing AU indicates increased degradation. *p<0.001, indicates statistical difference from 0% GA at that timepoint as assessed by a Bonferroni post test after a one-way ANOVA.

Figure 4

Cellular migration through crosslinked gels. Plots of cellular migration of (A) 3T3 fibroblasts, (B) RASMCs, (C) HCAECs on myocardial matrix gels of varied crosslinking %. *p<0.05 indicates statistical difference among groups by ANOVA for 3T3 migration, and statistical difference by t-test for RASMCs and HCAECs.