A Collagen-Chitosan Injectable Hydrogel Improves Cardiac Remodeling in a Mouse Model of Myocardial Infarction

Cardiac fibroblasts constitute the predominant cell type in the interstitium of the remodeling heart and play an essential role in the response to infarction. In this study, the effects of a collagen-chitosan matrix on cardiac fibroblast phenotype (in vitro) and cardiac remodeling (in vivo) were investigated. Mouse cardiac fibroblasts were cultured on fibronectin, collagen or collagen-chitosan matrix, and fibroblast phenotype was assessed in vitro. Fibroblasts on the collagen-chitosan matrix had a reduced number of alpha-SMA(+) cells and less deposition of fibrillar collagen, indicative of less myofibroblast differentiation. For in vivo experiments, 2 weeks after myocardial infarction (MI), mice were randomly allocated to receive local injections of collagen-chitosan matrix, collagen matrix or phosphate buffered saline. Cardiac function parameters (left ventricular ejection fraction and fractional shortening) were improved only in collagen-chitosan injected mice over a 3-week followup period. The collagen-chitosan matrix-treated hearts also had smaller infarct size, higher arteriole density, reduced CD68(+) cell infiltration, and decreased matrix metalloproteinase-9 and elevated tissue inhibitor of metalloproteinase-2 levels compared to the other groups. This study demonstrates the potential of the collagen-chitosan matrix for use as a stand-alone therapy to regulate cardiac fibroblasts, alter remodeling and enhance function of the MI heart.