Dissolvable antimicrobial microneedles loaded with bone marrow mesenchymal stem cell-derived migrasomes for diabetes wound treatment

In clinical settings, diabetic wounds present persistent challenges to spontaneous healing, primarily due to excessive inflammatory responses, impaired vascular perfusion, elevated levels of reactive oxygen species (ROS), and increased susceptibility to infection. In this context, transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has shown promising results in enhancing wound healing. Emerging evidence suggests that this therapeutic benefit is closely linked to the extracellular vesicles (EVs) secreted by BMSCs. Among the newly identified EV subtypes, migrasomes (Migs) have recently demonstrated significant roles in embryonic development, immune modulation, and tissue regeneration. Nevertheless, the specific biological functions and underlying molecular mechanisms of Migs under diabetic pathophysiological conditions remain largely unexplored. Previous studies have preliminarily revealed that BMSCs-Migs are capable of chemotactically recruiting ECs and BMSCs, as well as promoting anti-inflammatory macrophage polarization. However, achieving sustained release of these bioactive components at precise dermal depths to maximize their therapeutic effect remains a major obstacle. To address this issue, an innovative antimicrobial microneedle system (MNs@Mig) has been developed for transdermal, controlled delivery of BMSCs-Migs for diabetic wound therapy. This microneedle platform exhibits sufficient mechanical strength for effective skin penetration and enables prolonged release of therapeutic agents. The incorporation of Migs endows MNs@Mig with multifunctional properties tailored for the treatment of chronic diabetic wounds. By preventing bacterial colonization, recruiting various reparative cells, enhancing angiogenesis, reducing ROS accumulation, and modulating macrophage polarization, MNs@Mig facilitates accelerated, efficient, and high-quality wound repair. These findings underscore the potential of MNs@Mig as a multi-targeted and highly promising therapeutic strategy for diabetic wound management.