Decellularized extracellular matrix and mesenchymal stem cells promote recovery in traumatic brain injury by synergistically enhancing neurogenesis and attenuating neuroinflammation

Damaged neurons and harsh microenvironments contribute to the injury cascades following traumatic brain injury (TBI). Mesenchymal stem cell (MSC) therapy is considered a viable choice for brain injury treatment; however, its clinical use is hindered by limited engraftment, low survival ratio, and uncontrolled differentiation. Herein, the decellularized brain extracellular matrix (dBECM) was prepared through a new method as a delivery system for MSCs. dBECM-based hydrogel with favorable biochemical and biomechanical features provides a microenvironment for MSCs in nerve repair. The MSCs-encapsulated dBECM-based hydrogel is shown to improve neuron compensation and structural regeneration, alleviate neuroinflammation, and promote M1-to-M2 polarization of microglia. Our results first demonstrate that the combination of dBECM and MSCs is a critical vehicle to promote TBI repair from neurogenesis and immunoregulation, showing promise for the physiological recovery of neurogenic diseases and injuries.