Peripheral nerve adhesion occurs following injury and surgery. Functional impairment leading by peripheral nerve adhesion remains challenging for surgeons. Local tissue overexpression of heat shock protein (HSP) 72 can reduce the occurrence of adhesion. This study aims to develop a photothermal material polydopamine nanoparticles@Hyaluronic acid methacryloyl hydrogel (PDA NPs@HAMA) and evaluate their efficacy for preventing peripheral nerve adhesion in a rat sciatic nerve adhesion model. PDA NPs@HAMA was prepared and characterized. The safety of PDA NPs@HAMA was evaluated. Seventy-two rats were randomly assigned to one of the following four groups: the control group; the hyaluronic acid (HA) group; the polydopamine nanoparticles (PDA) group and the PDA NPs@HAMA group (n = 18 per group). Six weeks after surgery, the scar formation was evaluated by adhesion scores and biomechanical and histological examinations. Nerve function was assessed with electrophysiological examination, sensorimotor analysis and gastrocnemius muscle weight measurements. There were significant differences in the score on nerve adhesion between the groups (p < 0.001). Multiple comparisons indicated that the score was significantly lower in the PDA NPs@HAMA group (95% CI: 0.83, 1.42) compared with the control group (95% CI: 1.86, 2.64; p = 0.001). Motor nerve conduction velocity and muscle compound potential of the PDA NPs@HAMA group were higher than the control group's. According to immunohistochemical analysis, the PDA NPs@HAMA group expressed more HSP72, less α-smooth muscle actin (α-SMA), and had fewer inflammatory reactions than the control group. In this study, a new type of photo-cured material with a photothermic effect was designed and synthesized-PDA NPs@HAMA. The photothermic effect of PDA NPs@HAMA protected the nerve from adhesion to preserve the nerve function in the rat sciatic nerve adhesion model. This effectively prevented adhesion-related damage.
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