(32d) Extracellular Matrix-Integrated Hydrogels for Regenerative Medicine

The extracellular matrix (ECM) of tissues contains favorable biological molecules and properties that modulate cell behavior. The ECM-embedded biomolecules, such as proteins and growth factors, can regulate cell proliferation, migration, differentiation, and phenotypic expression. This regulation ultimately influences cell survival and tissue repair. As such, decellularized ECM has emerged as a potent therapeutic product for tissue regeneration. Traditionally, ECM is extracted by decellularizing tissues from allogeneic/xenogeneic sources. However, they are prone to batch-to-batch variation and adverse immune reactions, which can result in suboptimal tissue repair. Therefore, there is a critical need for innovation in the development of ECM-derived therapeutics for diverse biomedical applications. In this work, we have extracted ECM from in vitro 2D mammalian tissue cultures. We confirmed the removal of cells using scanning electron microscopy and DAPI staining. We utilized proteomics to thoroughly analyze the protein composition of the developed ECM. Next, we demonstrated the ability of the 2D tissue culture-derived ECM to differentiate stem cells towards desired lineages, making it a potent cell-directive therapeutic. We integrated this bioactive material into a gelatin-based biopolymer and 3D printed it with a digital light processing (DLP)-based 3D bioprinter. 3D printing enables the fabrication of patient-specific scaffolds, thereby increasing the applicability of the designed therapy. We also evaluated the physical, mechanical, and rheological properties of the 3D printed hydrogels and examined their in vitro cytocompatibility. Finally, the bioactivity of this hydrogel was evaluated in vitro using stem cells. Taken together, we envision that the designed therapeutic platform will advance ECM-derived regenerative therapies.