Microneedle-mediated delivery of Coptis chinensis-derived nanovesicles orchestrating antibacterial and macrophage reprogramming for comprehensive wound healing

Conventional antibiotic treatments for infected wounds often inadequately regulate the complex inflammatory cascade and fail to sufficiently promote tissue regeneration, leading to delayed healing and potential secondary tissue damage. Consequently, designing multifunctional biomaterials capable that can simultaneously exert antibacterial, anti-inflammatory, and pro-regenerative actions remains a critical challenge in wound management. In this study, we developed a soluble microneedle (MN) array loaded with nanovesicles derived from Coptis chinensis (CDVs), which serves as an integrated tri-functional platform to synergistically accelerate healing of infected wounds. The CDVs were effectively encapsulated within sodium alginate-based microneedles, with calcium ions introduced to reinforce structural crosslinking. Upon penetration into the wound bed, the MNs facilitated deep tissue delivery and sustained release of CDVs, which triggered a ROS burst inside bacteria, resulting in membrane disruption and bacterial eradication. Both in vitro and in vivo evaluations confirmed that the released CDVs promoted macrophage polarization toward the M2 phenotype and enhanced glucose uptake via the AMPK/mTOR pathway, thereby remodeling the inflammatory microenvironment and stimulating angiogenesis and tissue regeneration. Notably, in vivo wound healing assays demonstrated that the MN-mediated delivery of CDVs significantly enhanced repair outcomes compared to free vesicle treatment. This study highlights the rational integration of multifunctional plant-derived nanovesicles with a microneedle platform as a promising and translatable strategy for developing safe and effective therapeutics for infected wound healing.