Platelet-Rich Plasma Hydrogel Patch Promotes Hyperacute Cardioprotection after Myocardial Infarction

Abstract

Alternative therapies are needed for heart failure following myocardial infarction (MI), as ischemic cardiomyopathy remains a major global health concern despite advances in acute MI management. Platelet-rich plasma (PRP), which is enriched with cytokines and growth factors, holds therapeutic potential in ischemic cardiovascular diseases. However, its clinical application remains unrealized due to the absence of a reliable delivery approach. An epicardial patch provides a spatially stable delivery system on the heart surface. This approach becomes particularly attractive when combined with biodegradable controlled-release hydrogels that prolong and localize factor release. Therefore, combining these two modalities into an epicardial hydrogel patch offers a novel and efficient strategy for targeted PRP delivery. This study evaluated the feasibility and therapeutic efficacy of a biodegradable gelatin hydrogel patch, incorporating PRP and designed for epicardial use, in a rat MI model. PRP was prepared via double-spin centrifugation and activated with calcium chloride. In vitro, cytokine and growth factor levels (transforming growth factor-beta 1 [TGF-β1], platelet-derived growth factor-BB [PDGF-BB], insulin-like growth factor-1 [IGF-1], vascular endothelial growth factor [VEGF]) were quantified using enzyme-linked immunosorbent assay. PRP contained TGF-β1, PDGF-BB, and IGF-1; VEGF was undetectable. Release kinetics were measured under nonenzymatic and collagenase conditions. The hydrogel provided controlled release, especially of TGF-β1, for 5 days in vitro. In vivo, MI was induced by ligating the left anterior descending artery in rats. The epicardial hydrogel patch was placed at the infarct center, covering a fibrin–collagen sealant patch. The patch remained in place for 10 days and degraded by day 20. Cardiac function was evaluated via echocardiography through day 28, after which hearts were harvested for histological infarct analysis. Serial echocardiographic evaluations revealed that the PRP group demonstrated less decline in systolic function (fractional area change) from the hyperacute phase (day 1) to the chronic phase (day 28). Morphological assessments demonstrated that the PRP group had smaller left ventricular end-diastolic dimensions from day 7 onward. Histological evaluation confirmed greater infarcted wall thickness and myocardial area within the infarcted region compared with controls. Therefore, the epicardial delivery of PRP via a controlled-release hydrogel patch attenuated cardiac dysfunction from the hyperacute to the chronic phases and mitigated adverse ventricular remodeling.

Impact Statement

This study highlighted the cardioprotective effects of platelet-rich plasma (PRP) after myocardial infarction (MI) using a novel epicardial delivery system. A biodegradable hydrogel patch was specifically designed for stable and controlled PRP release from the cardiac surface. In a rat MI model, PRP attenuated systolic dysfunction during the hyperacute phase of MI and prevented adverse left ventricular remodeling in the chronic phase. A significant finding of this study was that PRP exerted a rapid cardioprotective effect as early as day 1 after MI. This PRP delivery platform may be an alternative therapy for ischemic heart disease.