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In this paper, a new synergistic treatment strategy based on ultrasound controlled release hydrogel is proposed to solve the problem of slow healing of diabetic wounds. By covalently conjugating calcitonin gene-related peptide (CGRP) with manganese porphyrin (MnP), a dual-action prodrug molecule MC with both neuroimmunomodulatory and reactive oxygen species (ROS) scavenging functions was constructed, which was further assembled into folic acid-targeted nanoparticle MCF and encapsulated in ultrasound-responsive sodium alginate hydrogel to form a MCF@CA intelligent delivery system. The system can achieve on-demand release of drugs under ultrasound triggering, and significantly improve the inflammatory microenvironment of diabetic wounds and accelerate collagen deposition and angiogenesis by targeting M1 macrophages, clearing excess ROS, promoting macrophage polarization to M2 phenotypes, and enhancing neuro-immune communication. The study, published in Advanced Science, provides a multi-mechanism synergistic precision intervention plan for the treatment of diabetic wounds.
