@article{Martin2026, 
author = {Vidmi Taolam Martin and Yanpeng Lin and Hangtian Wu and Bo Yu and Daogang Guan and Jun Wang and Bin Yu},
title = {An injectable AsCu-nanocomposite hydrogel breaks the pathological triad of acute osteomyelitis via synergistic bactericidal and macrophage-reprogramming therapy},
year = {2026},
journal = {Nano Research},
keywords = {bone regeneration, immunomodulation, macrophage polarization, osteomyelitis, nanocomposite hydrogel},
url = {https://www.sciopen.com/article/10.26599/NR.2026.94908539},
doi = {10.26599/NR.2026.94908539},
abstract = {The clinical failure of conventional osteomyelitis treatments often arises from their inability to concurrently eradicate biofilms, resolve chronic inflammation, and promote bone repair. Therefore, there is an urgent need for a therapeutic approach that simultaneously addresses infection, immune dysregulation, and tissue loss. This study aims to develop a multifunctional nanocomposite hydrogel (AsCu@Gel) that integrates antibacterial, immunomodulatory, and osteoinductive properties for the comprehensive treatment of acute Staphylococcal osteomyelitis (AOM). We engineered a thermosensitive hydrogel encapsulating Astaxanthin-Copper nanoparticles (AsCu@NPs). The material was characterized for its structure, multi-stimuli responsive release (pH, enzyme, temperature), and biocompatibility. Its efficacy was evaluated through in vitro antibacterial and anti-biofilm assays, analysis of macrophage polarization, and osteogenic differentiation studies. A mouse model of implant-associated AOM was used to validate the in vivo therapeutic effects, immune modulation, and bone preservation. The AsCu@Gel system demonstrated potent, pH-enhanced antibacterial and anti-biofilm activity. Crucially, it synergistically polarized macrophages from a pro-inflammatory M1 to a pro-healing M2 phenotype, significantly elevating IL-10, ARG1, and CD206 while suppressing TNF-α, IL-6, and iNOS. Network pharmacology and experimental validation revealed that this dual action downregulated key inflammatory pathways (e.g., TLR9, MAPK8) and upregulated osteogenic signals (e.g., AKT1). In vivo, AsCu@Gel effectively eradicated infection, resolved systemic and local inflammation, and preserved bone architecture, outperforming monotherapy controls. The AsCu@Gel platform represents a shift from simple antibacterial treatment to a comprehensive strategy of anti-infection, anti-inflammatory, and pro-regeneration. Simultaneously disrupting biofilms and reprogramming the immune microenvironment toward regeneration offers a promising and innovative solution for treating complex bone infections.}
}