Biohybrid Nanorobots Carrying Glycoengineered Extracellular Vesicles Promote Diabetic Wound Repair through Dual‐Enhanced Cell and Tissue Penetration

Considerable progress has been made in the development of drug delivery systems for diabetic wounds. However, underlying drawbacks, such as low delivery efficiency and poor tissue permeability, have rarely been addressed. In this study, a multifunctional biohybrid nanorobot platform comprising an artificial unit and several biological components is constructed. The artificial unit is a magnetically driven nanorobot surface modified with antibacterial 2‐hydroxypropyltrimethyl ammonium chloride chitosan, which enables the entire platform to move and has excellent tissue penetration capacity. The biological components are two‐step engineered extracellular vesicles that are first loaded with mangiferin, a natural polyphenolic compound with antioxidant properties, and then glycoengineered on the surface to enhance cellular uptake efficiency. As expected, the platform is more easily absorbed by endothelial cells and fibroblasts and exhibits outstanding dermal penetration performance and antioxidant properties. Encouraging results are also observed in infected diabetic wound models, showing improved wound re‐epithelialization, collagen deposition, angiogenesis, and accelerated wound healing. Collectively, a biohybrid nanorobot platform that possesses the functionalities of both artificial units and biological components serves as an efficient delivery system to promote diabetic wound repair through dual‐enhanced cell and tissue penetration and multistep interventions. A biohybrid nanorobot platform combining a magnetically driven nanorobot surface modified with 2‐hydroxypropyltrimethyl ammonium chloride chitosan and glycoengineered extracellular vesicles loaded with mangiferin is developed. It alleviates oxidative stress, improves endothelial cell and fibroblast functions, and promotes wound re‐epithelialization, collagen deposition, and angiogenesis through dual‐enhanced cell and tissue penetration, thus showing great promise for diabetic wound repair.