Can Losartan controlled release improve the bio-hybrid cardiac patch in preventing left ventricular pathological remodeling?

Acute myocardial infarction (AMI), commonly referred to as a heart attack, is a leading cause of cardiovascular morbidity and mortality. It typically results from a sudden reduction or complete obstruction of blood flow in an epicardial coronary artery, leading to ischemia and subsequent myocardial cell death. Following AMI, the heart undergoes a compensatory process known as left ventricular (LV) Pathological remodelling, which includes wall thinning, chamber dilation, and geometric distortion. While initially adaptive, prolonged remodelling can compromise cardiac function and ultimately progress to heart failure (HF). Current clinical strategies to limit pathological LV remodeling include pharmacological interventions (e.g., beta-blockers, angiotensin-converting enzyme inhibitors), surgical approaches (e.g., Dor and Batista procedures), and mechanical restraint devices (e.g., Acorn, Paracor). Although these treatments can offer partial functional recovery, many patients continue to deteriorate, progressing to end-stage HF. Furthermore, mechanical devices that encapsulate the heart may limit long-term efficacy due to foreign body response and lack of adaptability. In recent years, biodegradable cardiac patches have emerged as a promising strategy for providing temporary mechanical support and modulating the post-infarction remodeling process. Various patch designs have been evaluated in preclinical models, incorporating features such as embedded cells, the release of bioactive molecules, pre-vascularization, immunomodulation, and electrical conductivity. Despite differing approaches, a common conclusion is that patches offering mechanical reinforcement and supporting cell integration are more likely to preserve LV structure and function. In a previous study, D’Amore et al. developed a bilayer (BL) biohybrid cardiac patch composed of poly (ester carbonate urethane) urea (PECUU) and Extracellular Matrix (ECM) that improved ventricular function and neovascularization in rats when implanted two- and eight-weeks post-MI. This biohybrid approach combined the mechanical benefits of isotropic PECUU with the biological cues of ECM, underscoring the potential of integrated strategies.This project aims to develop and evaluate this cardiac patch composed of a biodegradable polymer, PECUU, and ECM derived from porcine myocardium. Toenhance the regenerative potential, first, we incorporated a drug delivery system into the patch design, within the ECM layer to enable sustained, site-specific drug release by encapsulating losartan potassium, an Angiotensin II receptor blocker (ARBs) commonly used in the treatment of hypertension and HF. Second, we introduced mechanical anisotropy to better mimic native myocardial mechanics and align patch anisotropy with native LV fiber orientation. Additionally, the patches were characterized in terms of their mechanical performance, kinetic degradation, drug release, and bioactivity in vitro.Further in vivo efficacy tests will be evaluated in a rat model of chronic myocardial infarction (MI) to determine the potential of the biohybrid patch in mitigating adverse ventricular remodeling and improving cardiac function.