Injectable hydrogels are a promising method to enhance repair in the heart after myocardial infarction (MI). However, few studies have compared different strategies for the application of biomaterial treatments. In this study, we use a clinically relevant mouse MI model to assess the therapeutic efficacy of different treatment protocols for intramyocardial injection of a recombinant human collagen III (rHCIII) thermoresponsive hydrogel. Comparing a single hydrogel injection at an early time point (3 h) versus injections at multiple time points (3 h, 1 week, and 2 weeks) post-MI revealed that the single injection group led to superior cardiac function, reduced scar size and inflammation, and increased vascularization. Omitting the 3 h time point and delivering the hydrogel at 1 and 2 weeks post-MI led to poorer cardiac function. The positive effects of the single time point injection (3 h) on scar size and vascular density were lost when the hydrogels collagen concentration was increased from 1% to 2%, and it did not confer any additional functional improvement. This study shows that early treatment with a rHCIII hydrogel can improve cardiac function post-MI but that injecting more rHCIII (by increased concentration or more over time) can reduce its efficacy, thus highlighting the importance of investigating optimal treatment strategies of biomaterial therapy for MI.
Funding Agencies|Canadian Institutes of Health Research (CIHR)Canadian Institutes of Health Research (CIHR); Natural Sciences and Engineering Research Council (NSERC)Natural Sciences and Engineering Research Council of Canada [CPG-158280, CHRP 523794-18]; CIHR operating grantCanadian Institutes of Health Research (CIHR) [MOP-77536]; Lawrence Soloway Endowed Fellowship from the University of Ottawa Heart Institute Foundation; Frederick Banting and Charles Best Canada Graduate Scholarship from the CIHRCanadian Institutes of Health Research (CIHR)