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

## TL;DR

A new vehicle-free composite material combining gallium and perfluoroalkyl substances promotes healing of infected wounds by reducing bacteria and inflammation.

## Contribution

A novel vehicle-free PFASs@Ga composite is developed for immunomodulatory wound healing with antibacterial and pro-healing properties.

## Key findings

- PFUnA@Ga shows potent antibacterial activity against MRSA and E. coli with enhanced wound closure.
- The composite modulates inflammation by reducing M1 macrophages and promoting M2 macrophages and angiogenesis.
- PFUnA@Ga demonstrates biocompatibility, biosafety, and superior performance compared to other PFASs@Ga composites.

## Abstract

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.

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•The vehicle-free PFASs@Ga composite integrates gallium-driven antibacterial activity to treat infected wounds without external delivery platforms.•PFUnA@Ga exhibits higher antibacterial activity, biofilm inhibition, and promotion of wound healing than other PFASs@Ga composites.•PFUnA@Ga shows outstanding biocompatibility and biosafety. Immunomodulatory effects include reduced inflammation and improved angiogenesis, supporting enhanced tissue regeneration and repair.

The vehicle-free PFASs@Ga composite integrates gallium-driven antibacterial activity to treat infected wounds without external delivery platforms.

PFUnA@Ga exhibits higher antibacterial activity, biofilm inhibition, and promotion of wound healing than other PFASs@Ga composites.

PFUnA@Ga shows outstanding biocompatibility and biosafety. Immunomodulatory effects include reduced inflammation and improved angiogenesis, supporting enhanced tissue regeneration and repair.