Fabrication of a Hybrid Cellularized Cardiac Patch via 3D Bioprinting of Alginate-Gelatin-PEOz Patterns on Electrospun PLCL-PEOz Nanofibers

Abstract

A cellular cardiac patch for treating Myocardial Infarction (MI) need to exhibit both structural fidelity and functional features for effective regeneration. To achieve a biomimetic patch, we report the development of a hybrid cellular cardiac patch by integrating electrospinning and extrusion-based three dimensional (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-Llactide-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 enhanced the Young's modulus (193±63 kPa), ultimate tensile strength (285±59 kPa) and long-term patch stability. In vitro studies of hybrid cardiac patch (AGP-B73) produced by bioprinting primary neonatal rat ventricular cardiomyocytes (NRVCMs) encapsulated in AGP bioink onto aligned B73 nanofibers surface demonstrate robust 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 proof of concept for the AGP-B73 cardiac patch as a promising candidate for MI treatment and potential drug testing applications.