Fabrication of a hybrid cellularized cardiac patch via 3D bioprinting of alginate-gelatin-PEOz patterns on electrospun PLCL-PEOz nanofibers

A cellular cardiac patch for treating Myocardial Infarction (MI) need to exhibit both structural fidelity and functional features for effective regeneration of the ischemic zone. To achieve a biomimetic patch, we report the development of a hybrid cellular cardiac patch by integrating electrospinning and extrusion-based 3D bioprinting. A thermoresponsive bioink composed of sodium alginate-gelatin-polyethyl oxazoline (AGP) bioink was optimized for direct printing onto an electrospun nanofiber support matrix. Electrospun aligned B73 (7:3 blend of poly-L-lactide-co-ε-caprolactone (PLCL) and polyethyl oxazoline (PEOz)) hydrophilic nanofibers was used as a support matrix, which offered oriented topographical cues & heterogenous nanofiber distribution. Following bioprinting, dual crosslinking using calcium chloride and microbial transglutaminase (TG) enhanced the Young’s modulus (193 ± 63 kPa), ultimate tensile strength (285 ± 59 kPa) and long-term patch stability. Invitro studies using primary neonatal rat ventricular cardiomyocytes (NRVCMs) demonstrated that the hybrid AGP-B73 hybrid cardiac patch supported cell viability, contractility, anisotropy and maturation. Evaluation using a 2D Hypoxia/Reoxygenation (H/R) in vitro model showed that patch implantation preserved NRVCMs viability under hypoxic stress. This study serves as a proof of concept for the AGP-B73 cardiac patch as a promising candidate for MI treatment and potential drug testing applications.