3D Structure and Processing Methods Direct the Biological Attributes of ECM-Based Cardiac Scaffolds

High hopes are held for cardiac regenerative therapy, driving a vast research effort towards the development of various cardiac scaffolds using diverse technologies and materials. Nevertheless, the role of factors such as fabrication process and structure in determining scaffold’s characteristics is yet to be discovered. In the present study, the effects of 3D structure and processing method on cardiac scaffolds are addressed using three distinct scaffolds made through different production technologies from the same biomaterial: decellularized porcine cardiac extracellular matrix (pcECM). pcECM patch, injectable pcECM hydrogel, and electrospun pcECM scaffolds were all proven as viable prospective therapies for MI, thus generally preserving pcECM beneficial properties. Yet, as we demonstrate, minor differences in scaffolds composition and micro-morphology as well as substantial differences in their mechanical properties, which arise from their production process, highly affect the interactions of the scaffold with both proliferating cells and functional cells. Hence, the rates of cell attachment, survival, and proliferation significantly vary between the different scaffolds. Moreover, major differences in cell morphology and alignment as well as in matrix remodeling are obtained. Overall, the effects revealed herein can guide a more rational scaffold design for the improved cellular or acellular treatment of different cardiac disease scenarios.