Biomaterial gels drive endogenous neurogenesis to support functional recovery after adult traumatic cortical injury

Activation and neuronal differentiation of endogenous neural stem/progenitor cells within the hippocampal neurogenic niche (a neurogenic region) of the adult mammalian brain are considered potential bases for restoration of cognitive and memory functions. However, following traumatic cortical brain injury (i.e., injuries in a non-neurogenic region), the local microenvironment becomes hostile due to the presence of inhibitory factors such as inflammation, edema, and hypoxic–ischemic stress. These conditions hinder the migration and subsequent neuronal differentiation of activated neural stem/progenitor cells into the injured cortex. Numerous recent studies have confirmed that biomaterials can improve the microenvironment of the injured area and promote nerve regeneration. In this study, we report the findings obtained by injecting a biodegradable chitosan–gelatin–collagen gel into the cortical lesion area. We observed that the chitosan–gelatin–collagen gel established a permissive microenvironment for neural repair by suppressing inflammation and scar infiltration while promoting neovascularization. Thus, it enabled activated endogenous “seed” cells, i.e., neural stem/progenitor cells, to migrate into the cortical lesion area and generate new neurons and thereby facilitate functional recovery. These findings represent a novel biomaterial-based therapeutic strategy for the treatment of traumatic cortical brain injury, stroke, and other neurological disorders.