Protein/polysaccharide-based scaffolds mimicking native extracellular matrix for cardiac tissue engineering applications

Tissue engineering has emerged as a viable approach to treat disease or repair damage in tissues and organs. One of the key elements for the success of tissue engineering is the use of a scaffold serving as artificial extracellular matrix (ECM). The ECM hosts the cells and improves their survival, proliferation, and differentiation, enabling the formation of new tissue. Here, we propose the development of a class of protein/polysaccharide-based porous scaffolds for use as ECM substitutes in cardiac tissue engineering. Scaffolds based on blends of a protein component, collagen or gelatin, with a polysaccharide component, alginate, were produced by freeze-drying and subsequent ionic and chemical crosslinking. Their morphological, physicochemical, and mechanical properties were determined and compared with those of natural porcine myocardium. We demonstrated that our scaffolds possessed highly porous and interconnected structures, and the chemical homogeneity of the natural ECM was well reproduced in both types of scaffolds. Furthermore, the alginate/gelatin (AG) scaffolds better mimicked the native tissue in terms of interactions between components and protein secondary structure, and in terms of swelling behavior. The AG scaffolds also showed superior mechanical properties for the desired application and supported better adhesion, growth, and differentiation of myoblasts under static conditions. The AG scaffolds were subsequently used for culturing neonatal rat cardiomyocytes, where high viability of the resulting cardiac constructs was observed under dynamic flow culture in a microfluidic bioreactor. We therefore propose our protein/polysaccharide scaffolds as a viable ECM substitute for applications in cardiac tissue engineering.