Soft hydrogel promotes dorsal root ganglion by upregulating gene expression of Ntn4 and Unc5B

Mechanical property is an important factor of cellular microenvironment for neural tissue regeneration. In this study, polyacrylamide (PAM) hydrogels with systematically varying elastic modulus were prepared using in situ radical polymerization. We found that the hydrogel was biocompatible, and the length of dorsal root ganglion (DRG)'s axon and cell density were optimal on the hydrogels with elastic modulus of 5.1 kPa (among hydrogels with elastic modulus between 3.6 kPa and 16.5 kPa). These DRGs also exhibited highest gene and protein expression of proliferation marker Epha4, Ntn4, Sema3D and differentiation marker Unc5B. Our study revealed the mechanism of how material stiffness affects DRG proliferation and differentiation. It will also provide theoretical basis and evidence for the design and development of nerve graft with better repair performance.