Biomechanically‐Adapted Immunohydrogels Reconstructing Myelin Sheath for Peripheral Nerve Regeneration

Abstract Myelin sheath reconstruction plays an important role in peripheral nerve regeneration. But the hindered reconstruction of myelin sheath, due to the inadequate repair phenotypes of macrophages and Schwann cells after peripheral nerve injury, often causes poor functional nerve recovery. Here, biomechanically‐adapted immunohydrogels are prepared as the FK506‐loaded platforms and nerve tissue engineering scaffolds to reconstruct myelin sheath for peripheral nerve regeneration. By immunofluorescent staining, an increase in the proportion of F4/80 + markers reveals that the biomechanically‐adapted scaffolds facilitate recruitment of macrophages. Furthermore, the high Interleukin 10 (IL‐10) mRNA expression level suggests the anti‐inflammation learning effects of FK506 in vitro, which is further confirmed by a high CD206/TNF‐ α ratio in the FK506 Gel group in vivo. The immune learning effects are positively related to the increase in compactness and thickness of myelin sheath, indicating the synergy of structural reconstruction of myelin sheath and M2 phenotype polarization of macrophages. All these data indicate that the biomechanically‐adapted immunohydrogels enhance recruitment of macrophages, educate M2 polarization of macrophages and promote a neuroprotective environment, which in consequence reconstructs myelin sheath for peripheral nerve regeneration.