Bio-Hybrid Cardiac Patches with Sustained Losartan Delivery: A Strategy Against Left Ventricular Remodeling

Abstract

Cardiac patches(CPs) offer a promising strategy to prevent adverse remodeling post-myocardial infarction.Previous studies demonstrated the efficacy of a biohybrid patch in a rat chronic infarction model at 8 and 16 weeks. This study aims to enhance that approach through controlled Losartan release and provides a complete in-vitro characterization of the patch prior to in-vivo testing. The biohybrid CP was fabricated using double-stream-electrospinning of Poly(ester-carbonate urethane) urea (PECUU) and cardiac-extracellular-matrix(ECM) gel derived from decellularized porcine hearts. Drug-loaded Poly (D,L-lactide-co-glycolide) (PLGA) microparticles (MPs) were embedded in the ECM-gel. Scanning-electron-Microscopy and digital image analysis were used to assess the patch’s microstructure. Cell vitality and proliferation were evaluated with AlamarBlue, and histological staining performed at pre-set intervals. Young’s Modulus, suture retention, uniaxial tensile testing and biaxial tensile test were measured for evaluating the biomaterial anisotropy. Moreover, degradation tests and Losartan release was assessed. Custom image analysis identified fiber orientation indices of 0.65 (ECM side) and 0.77 (polymer side), indicating alignment comparable to native rat left ventricle (OI=0.8). Mechanical testing confirmed anisotropy, with higher stiffness in the preferential direction (circumferential) (1.34MPa) vs longitudinal (0.89MPa) and anisotropic ratio of 2.32. Thickness was consistent (390±7.39µm). Viability assays and H&E staining confirmed the patch is non-toxic and supports cell growth and infiltration. Results demonstrate our capacity to couple the biohybrid approach (polymer rich/control on mechanics, ECM rich/bioactivity) with physiologically relevant anisotropy and with the controlled release of Losartan. Future in-vivo evaluation on rat coronary ligation model will be assessed