A vehicle-free immunomodulatory PFASs@Ga composite promotes the healing of infected wounds

Bacterial infection and severe inflammatory responses are major barriers to successful wound healing. Drug delivery systems have shown promise in precision medicine by enhancing the targeting and protection of therapeutic agents. However, their use is limited by challenges such as biocompatibility issues, structurally complex, high manufacturing costs, suboptimal drug loading, unstable release, and premature immune clearance. Although targeted delivery aims to improve efficacy, it may increase the risk of toxicity. Consequently, conventional non-carrier drugs often remain more practical and effective. Emerging vehicle-free systems with multifunctional capabilities show promise for precise targeting, controlled release, reduced toxicity, and simplified manufacturing. Here, we rationally designed and established a vehicle-free perfluoroalkyl material (PFAS)-gallium composites (PFASs@Ga) through introducing gallium (Ga) in PFASs, taking advantage of the collective merits of Ga's antibacterial and pro-healing properties and PFAS's well-recognized oxygen absorption, carrying of oxygen, chemical inertness, and tunable physicochemical properties. Extensive characterization showed well-defined morphology, elemental configuration, and distinct profiles of gallium ion release. The PFUnA@Ga composite improves gallium integration, Ga release, and O₂ delivery. This allowed it to demonstrate potent broad-spectrum antibacterial activity against bacteria, including MRSA and E. coli, which are known to be resistant. In a MRSA-infected wound model, PFUnA@Ga enhances wound closure and reduces bacterial load, thereby promoting regeneration and angiogenesis. The downregulation of pro-inflammatory M1 macrophages and the upregulation of anti-inflammatory M2 macrophages and CD31⁺ endothelial cells, representing immunomodulatory effects that facilitate inflammation resolution and vascularization. Results confirmed the composites' antibacterial activity and accelerated wound-healing efficacy. This multifunctional composite offers a novel approach for advanced wound management. More specifically, the synergistic approach combines metal-ion mediated bacterial inactivation with sustained oxygenation to support infection control and tissue repair.