A Dural Extracellular Matrix Hydrogel with Neural Stem Cells Improves Recovery from Traumatic Brain Injury in Mice

Current clinical treatment options for traumatic brain injury (TBI) to limit permanent tissue damage and secondary injury remain inadequate. Intraparenchymal transplantation of neural stem cells is a potentially powerful therapy for TBI, acting through replacement and/or protection of damaged cells. This approach could be augmented by entrapping the stem cells within a pro-regenerative hydrogel, designed to both retain the therapeutic cells at the transplant site and modulate the inflammatory response. This study reports a decellularized extracellular matrix hydrogel derived from porcine dura for this purpose and the assessment of its efficacy in vitro and in vivo. In vitro, the dural ECM hydrogel ameliorated oxidative stress in hypoxic astrocytes and influenced collagen remodeling in fibroblast-derived matrices. Proteomic characterization revealed a composition of 559 proteins within the dural ECM, alongside matrix-bound vesicles that were demonstrated to be distinct from traditional cell-derived exosomes. In vivo, mice subjected to a controlled cortical impact traumatic brain injury displayed improved motor recovery when treated with the hydrogel alone, neural stem cells in suspension, or their combination. This novel biomaterial shows promise as a new therapy for TBI treatment, both independently and as a vehicle for cell delivery.