Injectable Brain Extracellular Matrix Hydrogels Enhance Neuronal Migration and Functional Recovery After Intracerebral Hemorrhage

Neural repair within the lesion cavity caused by intracerebral hemorrhage (ICH) remains a major therapeutic challenge. Hydrogels hold great potential in regenerative medicine as functional scaffolds. However, inadequate host cell infiltration and suboptimal delivery methods have limited their application in tissue engineering. Here, we describe an optimized decellularization approach to create injectable brain extracellular matrix (ECM) hydrogels for the treatment of ICH. The hydrogel exhibits excellent biodegradability and biocompatibility. In an ICH rat model, the hydrogel implanted into the stroke cavity promoted neural recovery, facilitated cell recruitment, enhanced angiogenesis, and inhibited inflammation in the peri-cavity region at 14 d post-implantation. Furthermore, the hydrogel improved cell proliferation and migration, reversed cell apoptosis, and modulated transcriptomic changes in vitro. Notably, the hydrogel may promote neuronal migration and neural functional recovery after ICH through the slit guidance ligand 2-receptor roundabout guidance receptor 1 (Slit2-Robo1) signaling pathway. These findings highlight the potential of brain ECM hydrogels as a promising strategy for brain tissue regeneration.