Spatially Precise Neuron Formation via Hydrogel-Mediated Modulation of the Host Astrocyte Response

Abstract

The central nervous system exhibits limited capacity for regeneration following injury or disease. Although genetic and epigenetic reprogramming of non-neuronal cells into induced neurons offers a promising route for neuronal replacement and circuit reconstruction, its therapeutic potential remains constrained by low reprogramming efficiency and inadequate control over factor delivery. Here, we report a high-efficiency astrocyte-to-neuron reprogramming strategy enabled by ectopic expression of the transcription factor SOX2 delivered via adeno-associated viral vectors. We further engineered an implantable hybrid composite biomaterial that functions as a localized “reprogramming workshop”, per..