Abstract
Despite the success of current therapies for acute myocardial infarction (MI), many patients still develop adverse cardiac remodeling and heart failure. With the growing prevalence of heart failure, a new therapy is needed that can prevent remodeling and support tissue repair. Herein, we report on injectable recombinant human collagen type I (rHCI) and type III (rHCIII) matrices for treating MI. Injecting rHCI or rHCIII matrices in mice during the late proliferative phase post-MI restores the myocardium’s mechanical properties and reduces scar size, but only the rHCI matrix maintains remote wall thickness and prevents heart enlargement. rHCI treatment increases cardiomyocyte and capillary numbers in the border zone and the presence of pro-wound healing macrophages in the ischemic area, while reducing the overall recruitment of bone marrow monocytes. Our findings show functional recovery post-MI using rHCI by promoting a healing environment, cardiomyocyte survival, and less pathological remodeling of the myocardium.
Highlights
Despite the success of current therapies for acute myocardial infarction (MI), many patients still develop adverse cardiac remodeling and heart failure
The hydrogels are cross-linked in situ and assembled into a 3D matrix to provide a biomimetic niche for promoting endogenous repair within the infarcted myocardium
Several biomaterials based on natural extracellular matrix (ECM) proteins have been tested in animal models of MI and heart failure
Summary
Despite the success of current therapies for acute myocardial infarction (MI), many patients still develop adverse cardiac remodeling and heart failure. Restoring the ECM within the infarcted myocardium may help limit adverse remodeling and improve cardiac function[15,16], and injectable biomaterials have been proposed as therapies for this purpose[17,18,19,20,21]. Instead of using animal-derived components, we report the first injectable biomaterials made from recombinant human collagens type I (rHCI) and type III (rHCIII) in order to produce a clinically translatable material for cardiac therapy. These proteins have been previously used for the fabrication of corneal implants, which were demonstrated to be safe when transplanted in humans[34]. Intramyocardial injections of rHCI or rHCIII are administered to mouse hearts at 1-week post-
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