ArticleJournal of nanobiotechnology2026
All-in-one: a CGRP-encapsulated Rh-GelMA supramolecular dual-network hydrogel orchestrating immune-vascular coupling for diabetic wound healing.
Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Diabetic wounds present a complex pathological microenvironment that severely impairs healing. To address this challenge, we developed a supramolecular double-network hydrogel (CGRP@Rh-GelMA) consisting of a self-assembled rhein network and an in situ UV-crosslinked gelatin methacryloyl (GelMA) framework. This design endowed the hydrogel with strong mechanical robustness, wet-tissue adhesion, and sustained dual-drug release of rhein and calcitonin gene-related peptide (CGRP). In vitro, CGRP@Rh-GelMA exhibited broad-spectrum antibacterial activity and potent reactive oxygen species (ROS)-scavenging capacity. The hydrogel was also associated with reduced neutrophil extracellular trap (NETosis)-related markers, including myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit), as well as a shift in macrophage phenotype toward a reparative M2-like state, thereby contributing to a pro-healing immune microenvironment. In addition, CGRP@Rh-GelMA enhanced endothelial cell migration and vascular network formation in vitro, indicating pro-angiogenic potential. In a diabetic rat wound model, CGRP@Rh-GelMA accelerated wound repair, accompanied by improved immune microenvironment remodeling and neovascularization, resulting in enhanced granulation tissue formation, more organized collagen deposition, and re-epithelialization. Proteomic profiling further revealed inflammation-related pathway changes consistent with suppression of NF-κB signaling and NETosis. Collectively, these findings suggest that CGRP@Rh-GelMA is a mechanically robust and multifunctional biomaterial platform for diabetic wound healing by coordinately promoting immune and vascular repair responses.
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