Photopolymerizable Hydrogel for Enhanced Intramyocardial Vascular Progenitor Cell Delivery And Post-Myocardial Infarction Healing.

Cell transplantation success for myocardial infarction (MI) treatment is often hindered by low engraftment due to washout effects during myocardial contraction. A clinically viable biomaterial that enhances cell retention could optimize intramyocardial cell delivery. In this study, we developed a therapeutic cell delivery method for MI treatment utilizing a photocrosslinkable gelatin methacryloyl (GelMA) hydrogel. Human vascular progenitor cells, capable of forming functional vasculatures upon transplantation, were combined with an in-situ photopolymerization approach and injected into the infarcted zones of mouse hearts. Our strategy substantially improved acute cell retention and promoted long-term post-MI cardiac healing, including stabilized cardiac functions, preserved viable myocardium, and reduced cardiac fibrosis. Additionally, engrafted vascular cells polarized recruited bone marrow-derived neutrophils toward a non-inflammatory phenotype via TGFβ signaling, fostering a pro-regenerative microenvironment. Neutrophil depletion negated the therapeutic benefits generated by cell delivery in ischemic hearts, highlighting the essential role of non-inflammatory, pro-regenerative neutrophils in cardiac remodeling. In conclusion, our GelMA hydrogel-based intramyocardial vascular cell delivery approach holds promise for enhancing the treatment of acute myocardial infarction. This article is protected by copyright. All rights reserved.