Flexible Living Artificial Dura Mater for Efficient Therapy of Central Nervous System Injury Based on Neuronal Differentiation and Neuroprotective A2 Astrocyte Activation.

Abstract

Central nervous system (CNS) injury is one of the most serious public health problems worldwide. To prevent secondary cascade damages to CNS caused by dural defects, the repair of dural defects is an essential step in CNS injury treatment. Although various artificial dura maters have been developed, unfortunately, no one exerting positive therapeutic effects for CNS injury repair. Here, we suggested a flexible "living" artificial dura mater as a general strategy for CNS injury treatment by integrating the neural stem cells (NSCs) therapy and electrical stimulation. Under a rotating magnetic field based on magnetoelectric induction, NSCs seeded on a specially designed flexible patch with Au nanostrips produced therapeutic benefits to CNS injury. In vitro experiments prove that the magnetic field-driven Au nanostrips-mediated wireless electrical stimulation not only effectively accelerates NSCs differentiating into mature neurons with complex synaptic connections, but also induces astrocytes directionally activating into neuroprotective A2 reactive astrocytes. In vivo experiments with traumatic brain or spinal cord injury models confirm that the flexible living artificial dura mater shows optimal interface integration with tissue, effectively improving the immune microenvironment of the defect site, promoting the survival and differentiation of NSCs, and aiding the recovery of motor neural circuits after injury.