Cell-based therapy is currently the leading approach for the development of regenerative medicine platforms. Nevertheless, transplanted cells are often susceptible to the shear forces involved in the transplantation procedure and the change of microenvironment, and therefore, exhibit poor survival rates. The use of biomimetic delivery systems can also increase cell survival and re-acclimating in the tissue. Due to its unique bioactivity, porcine extracellular matrix (pECM) ―the natural bed of cells in the different tissues―holds a great promise as a biomaterial for cell-based therapies. To elaborate on the distinctive properties of pECM derived from different tissues, and their consequent ability to support cells, we decellularized and solubilized different porcine tissues and produced thermally induced pECM hydrogels. The obtained hydrogels varied in composition, structure, and mechanical properties. Consequently, the morphology and viability of mesenchymal stem cells (MSCs), as well as the spontaneous differentiation of human induced pluripotent stem cells (hiPSCs), cultured on the hydrogels, were considerably affected by the pECM origin. We have further produced spherical shape microscale carriers comprised solely of the solubilized pECM for the cardiac tissue regeneration. Upon seeding MSCs, these pECM-carriers supported cell viability and proliferation and supported hiPSCs viability and differentiation. To conclude, pECM-based cell delivery systems benefit unique, tissue-specific attributes that affect their properties, interactions with their resident cells, and generate a natural supportive bed for improved transplantation outcomes
