Myocardial infarction is one of the major causes of morbidity and mortality worldwide. Current treatments can relieve the symptoms of myocardial ischemia but cannot repair the necrotic myocardial tissue. Novel therapeutic strategies based on cellular therapy, extracellular vesicles, non-coding RNAs and growth factors have been designed to restore cardiac function while inducing cardiomyocyte cycle re-entry, ensuring angiogenesis and cardioprotection, and preventing ventricular remodeling. However, they face low stability, cell engraftment issues or enzymatic degradation in vivo, and it is thus essential to combine them with biomaterial-based delivery systems. Microcarriers, nanocarriers, cardiac patches and injectable hydrogels have yielded promising results in preclinical studies, some of which are currently being tested in clinical trials. In this review, we cover the recent advances made in cellular and acellular therapies used for cardiac repair after MI. We present current trends in cardiac tissue engineering related to the use of microcarriers, nanocarriers, cardiac patches and injectable hydrogels as biomaterial-based delivery systems for biologics. Finally, we discuss some of the most crucial aspects that should be addressed in order to advance towards the clinical translation of cardiac tissue engineering approaches.

Extracellular vesicles (EVs) are nanosized pArtículos with attractive therapeutic potential for cardiac repair. However, low retention and stability after systemic administration limit their clinical translation. As an alternative, the combination of EVs with biomaterial-based hydrogels (HGs) is being investigated to increase their exposure in the myocardium and achieve an optimal therapeutic effect. In this study, we developed and characterized a novel injectable in-situ forming HG based on alginate and collagen as a cardiac delivery vehicle for EVs. Different concentrations of alginate and collagen crosslinked with calcium gluconate were tested. Based on injectability studies, 1% alginate, 0.5 mg/mL collagen and 0.25% calcium gluconate HG was selected as the idoneous combination for cardiac administration using catheter-based systems. Rheological examination revealed that the HG possessed an internal gel structure, weak mechanical properties and low viscosity, facilitating an easy administration. In addition, EVs were successfully incorporated and homogeneously distributed in the HG. After administration in a rat model of myocardial infarction, the HG showed long-term retention in the heart and allowed for a sustained release of EVs for at least 7 days. Thus, the combination of HGs and EVs represents a promising therapeutic strategy for myocardial repair. Besides EVs delivery, the developed HG could represent a useful platform for cardiac delivery of multiple therapeutic agents.