MSC-Encapsulating in Situ Cross-Linkable Gelatin Hydrogels To Promote Myocardial Repair

Current
stem cell-based therapy for cardiac repair and regeneration
after myocardial infarction (MI) is not readily translatable into
clinical scenarios due to the low retention and survival of the transplanted
cells. Here, we evaluated a simple and feasible design of gelatin–hydroxyphenyl
propionic acid (GH) hydrogel as an in situ cross-linkable and injectable
cell delivery platform for cardiac tissue regeneration. The GH hydrogel
exhibited improved cell retention and survival in vitro and in vivo
when encapsulating mouse bone marrow-derived mesenchymal stem cells
(MSCs) that were used as promising therapeutic candidates for stem
cell therapy. Moreover, we demonstrated that MSC-encapsulating GH
hydrogels led to a significant improvement in cardiac functional metrics,
such as the fractional shortening (FS), ejection fraction (EF), and
end-systolic volume (ESV). Similarly, MSC-encapsulating GH hydrogels
induced favorable effects in the cardiac structures of the infarcted
heart, producing less fibrosis and thicker infarcted walls. These
results suggest that GH hydrogels can be used as an instructive cell
delivery platform to provide a suitable microenvironment for transplanted
cells; therefore, their in vivo applications combined with MSCs may
provide great potential for repair and regeneration of injured cardiac
tissues after MI.