Cardiac Matrix-Derived\nGranular Hydrogel Enhances\nCell Function in 3D Culture

Hydrogels derived from decellularized porcine myocardial\nmatrix\nhave demonstrated significant potential as therapeutic delivery platforms\nfor promoting cardiac repair after injury. Our previous study developed\na fibrin-enriched cardiac matrix hydrogel to enhance its angiogenic\ncapacities. However, the bulk hydrogel structure may limit their full\npotential in cell delivery. Recently, granular hydrogels have emerged\nas a promising class of biomaterials, offering unique features such\nas a highly interconnected porous structure that facilitates nutrient\ndiffusion and enhances cell viability. Several techniques have been\ndeveloped for fabricating various types of granular hydrogels, among\nwhich extrusion fragmentation is particularly appealing due to its\nadaptability to many types of hydrogels, low cost, and high scalability.\nIn this study, we first confirmed the effects of the bulk cardiac\nmatrix hydrogel on the viability of encapsulated human umbilical vein\nendothelial cells and human mesenchymal stem cells. We then tested\nthe feasibility of producing granular hydrogels from both cardiac\nmatrix and fibrin-enriched cardiac matrix through cellular cross-linking\nof microgels fabricated by extrusion fragmentation. Afterward, we\nexamined the roles of the produced granular hydrogels in the embedded\ncells and cell spheroids. Our <i>in vitro</i> data demonstrate\nthat cardiac matrix-derived granular hydrogels support optimal viability\nof encapsulated cells and promote sprouting of human mesenchymal stem\ncell spheroids. Additionally, granular hydrogel derived from fibrin-enriched\ncardiac matrix accelerates angiogenic sprouting of embedded human\nmesenchymal stem cell spheroids. The results obtained from this study\nlay an important foundation for the future exploration of using cardiac\nmatrix-derived granular hydrogels for cardiac cell therapy.