Chiral hydrogels facilitate rapid diabetic wound healing by promoting macrophage M2 polarization and cellular proliferation

Macrophage M2 polarization is one of the most important processes for promoting diabetic wound healing, but how chirality regulates this process is still unknown. Thus, chiral hydrogels based on amino acid derivatives (L-Fmoc-NV and D-Fmoc-NV) were applied to investigate the influence of chirality on macrophage M2 polarization. Compared to the right-handed nanofibers of D-Fmoc-NV, the left-handed helical nanofibers of L-Fmoc-NV can significantly affect the polarization of macrophages towards the M2 phenotype. Furthermore, the left-handed helical nanofibers of L-Fmoc-NV can more significantly promote cell adhesion, proliferation, and antibacterial responses than the nanofibers of D-Fmoc-NV. Based on these advantages of the left-handed helical nanofibers of L-Fmoc-NV, a more expedited healing trajectory (∼14 days) was observed in the L-Fmoc-NV systems. This work offers a new approach for chronic diabetic wound healing via the chirality-induced polarization of macrophages towards the M2 phenotype.