Hyaluronic acid-based hydrogel induces neovascularization and improves cardiac function in a rat model of myocardial infarction

OBJECTIVE: The use of stem cells in cardiac regeneration is still limited due to low cellular integration and engraftment rates. Consequently, there has been a spurt in research on developing alternative regenerative therapies. Hyaluronic acid (HA) is a major component of the extracellular matrix that is non-immunogenic, and has been implicated in various wound-healing functions such as angiogenesis and inflammation modulation, making it an ideal candidate for regenerative biomaterials. In this study, we examine the potential of acellular hyaluronic acid-based hydrogel in improving cardiac function post-myocardial infarction in a rat model. METHODS: Hyaluronic acid-based hydrogel was injected into the peri-infarct region post-myocardial infarction induction in Lewis rats. Cardiac function in control (n = 10) and gel-injected groups (n = 10) was evaluated up to 4 weeks post-myocardial infarction. Evaluation of cardiac function was conducted using transthoracic echocardiography. Histological analysis of scar area was evaluated via haematoxylin and eosin (H & E), and Sirius red staining. Neovascularization was detected using vascular endothelial growth factor (VEGF) staining. RESULTS: Evaluation of cardiac function using transthoracic echocardiography revealed a 18.2% (P < 0.01) increase in ejection fraction in gel-injected groups when compared with the control group, almost returning the ejection fraction to baseline levels (preop). Histological analysis of scar area by haematoxylin and eosin (H&E), and Sirius red staining demonstrated decreased scarring, and a 22.6% (P < 0.01) decrease in collagen deposition in the gel-injected group compared with the control group. VEGF staining indicated a significant increase in novel vasculature formation in hydrogel-injected groups when compared with control. CONCLUSION: Due to its regenerative potential, hyaluronic acid-based hydrogel provides a promising novel therapy to be used alone, or as a scaffold delivering a variety of drugs or cells to combat heart disease in a multifaceted approach.