PRP-loaded pH-responsive hydrogel for the amelioration of ventricular remodeling following myocardial infarction

The incidence and mortality rates of myocardial infarction (MI) worldwide have exhibited a sustained upward trend. Platelet-rich plasma (PRP) is enriched with a diverse repertoire of growth factors that promote cellular proliferation, revascularization and tissue repair, thereby emerging as a promising therapeutic modality for improving MI prognosis. However, the short half-life and inherent tendency of these growth factors to undergo rapid inactivation have hitherto constrained the clinical translation of PRP. Medical hydrogels are regarded as promising platforms for cardiac tissue engineering and localized drug delivery in the context of MI. Herein, we developed a polyethylene glycol-succinimidyl ester/poly-L-lysine (PEG-NHS/PLL) hydrogel engineered for the integration of PRP. The hydrogel strength could be tailored by adjusting the PLL and PEG-NHS ratio to match individualized post-MI treatment needs, while the optimal gelation time (5-10 s) facilitated clinical translation. Electrostatic interactions between the cationic moieties of PLL and PRP-derived bioactive factors contribute to their sustained and controlled release. Moreover,the hydrogel exhibited a faster release rate of PRP under acidic conditions and demonstrated excellent pH-responsive sustained-release properties. The PEG-NHS/PLL hydrogel facilitated the restoration of cardiac function after MI by suppressing fibrotic remodeling, reducing cardiomyocyte apoptosis, scavenges reactive oxygen (ROS) species and promoting neovascularization.