Peripheral Nerve‐Derived Matrix Hydrogel Promotes Remyelination and Inhibits Synapse Formation

Abstract Regeneration of injured nerve tissues requires intricate interplay of complex processes like axon elongation, remyelination, and synaptic formation in a tissue‐specific manner. A decellularized nerve matrix‐gel (DNM‐G) and a decellularized spinal cord matrix‐gel (DSCM‐G) are prepared from porcine sciatic nerves and spinal cord tissue, respectively, to recapitulate the microenvironment cues unique to the native tissue functions. Using an in vitro dorsal root ganglion–Schwann cells coculture model and proteomics analysis, it is confirmed that DNM‐G promotes far stronger remyelination activity and reduces synapse formation of the regenerating axons in contrast to DSCM‐G, Matrigel, and collagen I, consistent with its tissue‐specific function. Bioinformatics analysis indicates that the lack of neurotrophic factors and presence of some axon inhibitory molecules may contribute to moderate axonal elongation activity, while laminin β2, Laminin γ1, collagens, and fibronectin in DNM‐G promote remyelination. These results confirm that DNM‐G is a promising matrix material for peripheral nerve repair. This study provides more insights into tissue‐specific extracellular matrix components correlating to biological functions supporting functional regeneration.