Injectable and Self-Healable Thermoresponsive Hybrid Hydrogel Constructed via Surface-Modified Graphene Oxide Loading Exosomes for Synergistic Promotion of Schwann Cells

Abstract

Based on the excellent photothermal conversion performance of graphene oxide (GO) and the shrinkage of thermoresponsive copolymer chain segments, a GO–polymer hybrid hydrogel carrier system was designed to load stem cell exosomes that have repair and nutritional functions on nerve cells and play a synergistic role in the proliferation and migration of Schwann cells (SCs). The surface modification of hydroxypropyl chitosan on GO was carried out based on the EDC reaction, and GO–hydroxypropyl chitosan (GC) with well hydrophilicity and dispersion was obtained. The thermoresponsive copolymer poly(2-hydroxyethyl methacrylate- co -2-(2-methoxyethoxy) ethylmethacrylate- co -oligo(ethylene glycol) monomethyl ether methacrylate) (P(HEMA- co -OEGMA- co -MEO 2 MA), PHOM) was prepared by atom transfer radical polymerization. After aldehyde modification, PHOM–CHO was cross-linked with GC through a dynamic Schiff base bond to form a thermoresponsive hydrogel. Due to the near-infrared (NIR) photothermal conversion of GO and the thermoresponsive contraction of the hydrogel network, the hydrogel can achieve controlled release of the loaded exosomes. Cell experiments showed that the GO–thermoresponsive polymer hybrid hydrogel had good biocompatibility. Further tests on the promoting effect of the exosome-loaded hydrogel on Schwann cells (SCs) showed that the exosomes could be released in a controlled way through NIR irradiation, and the synergistic effect of exosomes and the GO hybrid hydrogel promoted the proliferation and migration of SCs.