Engineering Neural Stem Cells with Micropatches for Improved Therapy of Traumatic Brain Injury

Transplantation of neural stem cells (NSCs) holds promise for repairing traumatic brain injury (TBI) but their therapeutic performance is hindered due to the low efficient differentiation into neurons. Direct injection of differentiation modulators to the lesion site has limited improvement to neuronal differentiation as they tend to diffuse or be degraded. In the present study, we report a simple and versatile strategy to engineer the NSCs with a micropatch to improve their therapeutic performance in TBI treatment. The micropatches are fabricated through microcontact printing technique and can adhere to the membrane with negligible detachment or internalization within 14 days after surface modification. The micropatches on the cell membrane can move together with stem cells and sustainedly release retinoic acid, a neuronal differentiation modulator, to regulate the surrounding microenvironment of NSCs, improving their neuronal differentiation rate from 28.0% to 54.2%. The micropatch-engineered NSCs can be implanted into the injured brain tissue through a minimally invasive microinjection approach and show outperformance in repairing damaged neural tissue of TBI mice compared to normal stem cells. Overall, this work highlights a new pathway to engineer stem cells and holds great potential in nerve regeneration and neurodegenerative disease treatment.