Photothermal Controlled‐Release Immunomodulatory Nanoplatform for Restoring Nerve Structure and Mechanical Nociception in Infectious Diabetic Ulcers

Infectious diabetic ulcers (IDU) require anti-infection, angiogenesis, and nerve regeneration therapy; however, the latter has received comparatively less research attention than the former two. In particular, there have been few reports on the recovery of mechanical nociception. In this study, a photothermal controlled-release immunomodulatory hydrogel nanoplatform is tailored for the treatment of IDU. Due to a thermal-sensitive interaction between polydopamine-reduced graphene oxide (pGO) and the antibiotic mupirocin, excellent antibacterial efficacy is achieved through customized release kinetics. In addition, Trem2+ macrophages recruited by pGO regulate collagen remodeling and restore skin adnexal structures to alter the fate of scar formation, promote angiogenesis, accompanied by the regeneration of neural networks, which ensures the recovery of mechanical nociception and may prevent the recurrence of IDU at the source. In all, a full-stage strategy from antibacterial, immune regulation, angiogenesis, and neurogenesis to the recovery of mechanical nociception, an indispensable neural function of skin, is introduced to IDU treatment, which opens up an effective and comprehensive therapy for refractory IDU.