Facilitation of Cell Cycle and Cellular Migration of Rat Schwann Cells by O-Carboxymethyl Chitosan to Support Peripheral Nerve Regeneration.

ABSTRACT

O-carboxymethyl chitosan (CM-chitosan), holds high potential as a valuable biomaterial for nerve guidance conduits (NGCs). However, the lack of explicit bioactivity on neurocytes and poor duration that does not match nerve repair limit the restorative effects. Herein, CM-chitosan-based NGC is designed to induce the reconstruction of damaged peripheral nerves without addition of other activation factors. CM-chitosan possesses excellent performance in vitro for nerve tissue engineering, such as increasing the organization of filamentous actin and the expression of phospho-Akt, and facilitating the cell cycle and migration of Schwann cells. Moreover, CM-chitosan exhibits increased longevity upon cross-linking (C-CM-chitosan) with 1, 4-Butanediol diglycidyl ether, and C-CM-chitosan fibers possess appropriate biocompatibility. In order to imitate the structure of peripheral nerves, multichannel bioactive NGCs are prepared from lumen fillers of oriented C-CM-chitosan fibers and outer warp-knitted chitosan pipeline. Implantation of the C-CM-chitosan NGCs to rats with 10-mm defects of peripheral nerves effectively improve nerve function reconstruction by increasing the sciatic functional index, decreasing the latent periods of heat tingling, enhancing the gastrocnemius muscle, and promoting nerve axon recovery, showing regenerative efficacy similar to that of autograft. The results lay a theoretical foundation for improving the potential high-value applications of CM-chitosan-based bioactive materials in nerve tissue engineering.