Hybrid amphiphilic bimodal hydrogels having mechanical and biological recognition characteristics for cardiac tissue engineering

Abstract

Tissue engineering strategies rely on the favourable microniche scaffolds for 3D cell growth. For cardiac tissue engineering, a biodegradable hydrogel has to meet the essential requirements viz. adequate strength, compatibility of degradation products to the host tissue, maintenance of cellular viability and differentiation, favouring cell integration, controlled degradation of scaffold commensurate with the contractile function under ischemic conditions of the injured heart. In this work, an attempt is made to explore some of these stringent and diagonally opposite requirements. Hybrid amphiphilic bimodal hydrogels having mechanical and biological recognition characteristics were developed using graft comacromer of alginate-poly(mannitol fumarate-co-sebacate). Alginate was graft copolymerized with poly(mannitol fumarate-co-sebacate) macromer (HT-MFS). The resultant comacromer was crosslinked with PEGDA and DEGDMA to form two bimodal hydrogel scaffolds. Both hydrogels exhibited better physiochemical and mechanical properties and supported long-term cell viability under static and dynamic conditions. Laser scanning confocal microscopy Z-stacking evaluations showed infiltration of FDA-stained L929 fibroblasts in the interstices of the hydrogels with appreciable depth. The hydrogel based on PEGDA promoted cell growth to an extent of 98 μm when compared to that of DEGDMA based hydrogel with 52 μm. These hydrogels supported the co-culture of fibroblasts and cardiomyoblasts and provided a better microniche for the cells as evident by the viability and cell cycle progression analyses. The favourable cellular responses of these hydrogels are attributed to the inherent biological recognition characteristics. On comparing the two hydrogels, the PEGDA-based hydrogel was superior to its DEGDMA counterpart due to the higher hydrophilicity of the former. The PEGDA-based hydrogel is a promising candidate for cardiac tissue engineering.