Citation: Lv Geng, Xiaoya Yu, Xinyue Lei, Xiaoju Zhou. Transdermal delivery of engineered exosomes for diabetic wound healing: Driving M2 macrophage polarization[J]. Chinese Chemical Letters, ;2026, 37(12): 113079. doi: 10.1016/j.cclet.2026.113079 shu

Transdermal delivery of engineered exosomes for diabetic wound healing: Driving M2 macrophage polarization

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Science, Wuhan University, Wuhan 430071, China

xjzhou@whu.edu.cn

Received Date: 20 March 2026
Revised Date: 11 June 2026
Accepted Date: 12 June 2026
Available Online: 13 June 2026

Figures(5)

Impaired diabetic wound healing is a major complication of diabetes, primarily driven by persistent inflammation resulting from dysregulated macrophage polarization. Exosomes are cell-derived extracellular vesicles carrying diverse active cargoes. Exosomes from specific origins represent a promising cell-free option for diabetic wound healing, with their capacity to induce M2 macrophage polarization serving as a key therapeutic mechanism to resolve the chronic inflammation. However, the therapeutic efficacy of naïve exosomes is constrained by inherent limitations, including suboptimal levels of active cargo, poor stability in the wound microenvironment, and insufficient targeting specificity. To address these challenges, transdermal delivery of engineered exosomes had recently been developed. This review provides a comprehensive overview of recent advances in the application of these systems for promoting diabetic wound healing through precise regulation of macrophage polarization. Key strategies discussed include cargo loading techniques, surface modification for enhanced targeting, and integration with localized delivery platforms such as hydrogels, microneedles, porous sponges, three dimensions (3D)-printed scaffolds and metal-organic framework (MOF)-based scaffolds. By improving exosome stability, retention, targeting ability, and controlled release combined with the co-delivery of therapeutic cargo, these platforms collectively facilitate M2 macrophage polarization, optimize the wound microenvironment, and accelerate healing. Finally, we highlight current challenges and outline future directions, aiming to establish a theoretical foundation for next-generation immunomodulatory therapies leveraging engineered exosomes to induce M2 macrophage polarization for diabetic wound treatment.
- Diabetic wound,
- Exosomes,
- Macrophage polarization,
- Drug delivery system,
- Transdermal delivery
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沈阳化工大学材料科学与工程学院沈阳 110142