Homologous membrane wrapped ZIF‐8 nanoparticles accelerate differentiation of neural stem cell for spinal cord injury therapy

Abstract Spinal cord injury (SCI), particularly the traumatic type, is characterized by the loss of nerve cells and leads to neurological deficits that often impair lower limb function. Although endogenous neural stem cells (NSCs) possess innate regenerative potential, their therapeutic utility is hindered by poor differentiation efficiency and slow maturation within the hostile lesion microenvironment. Zinc ions regulate NSC differentiation; however, their therapeutic potential is restricted by the difficulty in achieving precise accumulation within NSCs. This study proposes a novel approach using ZIF‐8 nanoparticles, which are degraded in lysosomes under acidic conditions, generating zinc ion influx through endocytosis. Additionally, ZIF‐8 nanoparticles are coated with stem cell membranes to enhance targeted binding and improve endocytosis. In vitro results show that membrane‐coated ZIF‐8 accelerates neuronal differentiation by over 5 d, increasing the proportion of neurons by 10 times compared to spontaneous differentiation. RNA sequencing analysis reveals that the highly efficient regulation was mainly related to the calcium and the mitogen‐activated protein kinase signaling pathways. In vivo, membrane‐coated ZIF‐8 nanoparticles promote the motor, sensory, and autonomic function recovery of limbs in SCI mice, preventing glial scar formation. This innovative strategy of wrapping ZIF‐8 with cell membranes offers significant potential for advancing nerve injury repair.