A bio-orthogonally functionalized chitosan scaffold with esterase-activatable release for nerve regeneration.

Developing nerve conduits with biological cues is a promising approach for repairing peripheral nerve injuries. Although most biological cues incorporated into conduits generally exert their biological functions at the surface, they could not be released into the on-demand regeneration sites under physiological conditions. Herein, we firstly report a bio-orthogonally functionalized chitosan scaffold with esterase-activatable release for peripheral nerve regeneration. In this study, biological cues are not only selectively conjugated into nerve conduits by bio-orthogonal reaction, but also precisely released in on-demand regeneration sites via esterase-activatable cleavage for peripheral nerve repair. Moreover, this nerve scaffold with esterase-activatable release could promote Schwann cells proliferation. In a rat sciatic nerve defect model, the bio-orthogonally functionalized scaffold with esterase-activatable release significantly increased sciatic nerve function recovery and improved target muscles weight. This strategy of incorporating esterase-activatable bioactive cues into peripheral nerve conduits offers great potential in preclinical studies.