Light-responsive hydrogel delivers extracellular vesicles for improved wound healing

Extracellular vesicles, or EVs, are tiny membrane-bound particles released by cells. They carry proteins, nucleic acids, and other biological molecules that can influence the behavior of nearby or distant cells. EVs produced by stem cells have attracted particular interest for regenerative medicine because they can deliver signals involved in tissue repair.

Researchers from Nankai University have investigated a new way to deliver stem cell-derived extracellular vesicles directly to wounds and control when they are released.

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This study reports a spatiotemporal delivery system that liberates stem cell-derived EVs from an in situ forming adhesive hydrogel for rapid tissue repair. This multifunctional hydrogel exhibits synergistic antibacterial (99.9% against MRSA) and hemostatic effects, accelerates >90% full-thickness acute wound closure in 14 days, and effectively reduces scar formation, offering a precise and versatile strategy for wound therapy.

The challenge of delivering EVs to wounds

Stem cell-derived EVs have shown potential for promoting wound healing, but simply applying them to an injury presents an important problem. EVs can be rapidly cleared from the wound, limiting how long their biological cargo can interact with damaged tissue.

Biomaterials such as hydrogels can help keep EVs at the treatment site. However, conventional systems generally release their contents passively. This provides limited control over when EVs become available as the wound progresses through different stages of healing.

The researchers developed a hydrogel designed to address both challenges, keeping extracellular vesicles at the wound while allowing their release to be controlled using light.

Creating a hydrogel directly on the wound

The hydrogel begins as a material that can be applied directly to an acute wound. Exposure to 405 nm light causes it to form a gel at the wound surface.

Because the hydrogel forms in place, it can conform to irregular wound shapes rather than requiring a preformed dressing with a fixed geometry. The resulting adhesive scaffold covers the wound while holding stem cell-derived extracellular vesicles within its polymer network.

The researchers designed the material to be biocompatible so that the incorporated EVs could remain biologically active after being placed inside the hydrogel.

Using light to control extracellular vesicle release

A key feature of the system is its ability to release EVs when stimulated with near-infrared, or NIR, light.

Instead of relying entirely on passive release, NIR stimulation allows extracellular vesicles to be released from the hydrogel when desired. Laboratory experiments confirmed that the system responded to NIR light and that the released EVs maintained their biological activity.

This provides researchers with both spatial and temporal control over EV delivery. The hydrogel determines where the vesicles are delivered, while light helps control when they become available to the surrounding tissue.

Improving wound repair

The researchers evaluated the system in two acute wound models, full-thickness excision wounds and deep second-degree burns.

Compared with treatment using extracellular vesicles alone or the hydrogel alone, the combined system substantially accelerated tissue regeneration. The researchers also observed increased angiogenesis, the formation of new blood vessels needed to supply healing tissue with oxygen and nutrients.

Importantly, wounds treated with the EV-containing hydrogel also showed reduced scar formation.

These results suggest that retaining extracellular vesicles at the injury site and controlling their release may allow their regenerative signals to be used more effectively than simply applying EVs directly to a wound.

Toward more controlled extracellular vesicle therapies

Extracellular vesicles are being investigated as potential therapeutic tools because they can deliver complex biological signals without requiring transplantation of the cells that produced them. However, effective delivery remains an important challenge for translating EV-based therapies into clinical applications.

The light-responsive hydrogel provides one potential solution by combining localized EV retention with controlled release. Its ability to form directly on wounds also allows the material to adapt to injuries with different shapes and sizes.

Further research will be needed to determine how the system performs in human wounds and how it could be incorporated into clinical treatment. Still, combining stem cell-derived extracellular vesicles with responsive biomaterials could provide a useful strategy for delivering regenerative signals precisely where and when they are needed.

Kang J, Yin Y, Wang X, Li J, Wang Z, Li W, Du R, Chen J, Xu J, Jiang Y, Yang M, He M, Cai H, Liu D. (2026) Spatiotemporal delivery of stem cell-derived extracellular vesicles for rapid wound healing. Angewandte Chemie [article]

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