A materiobiology-inspired sericin nerve guidance conduit extensively activates regeneration-associated genes of Schwann cells for long-gap peripheral nerve repair

Abstract

Peripheral nerve injury (PNI) is one of the most common causes of adult disability. Following PNI, Schwann cells (SCs) dedifferentiate, proliferate, and upregulate a variety of regeneration-associated genes (RAGs), including neurotrophic factors, ultimately promoting nerve regeneration. Even though certain reported biomaterials could upregulate one or several neurotrophic factors of SCs, none of them was able to activate these RAGs extensively. Herein, this work represents a novel manganese organic framework material (Mn-MOF) capable of effectively upregulating RAGs of SCs. In vitro cell coculture assay revealed that these Mn-MOF treated SCs enhanced the axon extension of PC12 cells, further confirming the axon regeneration-promoting activity of this framework. STAT3 and C-JUN signaling pathways were involved in Mn-MOF-induced RAGs activation. Using sericin, a well-proved biomaterial with neuroprotective properties, a Mn-MOF modified sericin conduit (MOF-SS) was prepared via π-π interactions between the cyclobenzene of framework materials and the aromatic acid of natural proteins. The microstructures and physiochemical properties of MOF-SS were comprehensively characterized, and its RAGs-activating effect on SCs was well confirmed. When applied in vivo to bridge 13-mm sciatic nerve defect, this conduit significantly promoted nerve microstructural regeneration, enhanced electrical conduction performance of regenerated nerve, improved functional recovery, and more importantly, alleviated muscle atrophy. In summary, this work represents a novel Mn-MOF modified sericin conduit capable of extensively activating RAGs of SCs, significantly promoting long-gap PNI repair.