Sprayable bioadhesive microcarriers loaded with Tβ4-Engineered ADSC exosomes for diabetic wound healing

Stem cell-derived therapeutics show strong potential to recalibrate diabetic wound immunity, yet their stability, retention, and practical usability remain major barriers to effective application. Here, we report a novel microcarrier platform loaded with thymosin β4 (Tβ4)-overexpressing stem cell-derived exosomes for a sprayable diabetic wound dressing. Adipose-derived stem cells (ADSCs) were genetically engineered to overexpress Tβ4, generating potent immunoregulatory exosomes that were efficiently encapsulated into uniform, micron-scale hydrogel microcarriers via microfluidic fabrication and further functionalized with a mesoporous polydopamine (mPDA) coating to enhance wet adhesion and tissue retention. The resulting EXOs^Tβ4/mPDA@MS system stabilizes the exosome payload and enables convenient spray-based wound administration. These microcarriers provide sustained, localized exosome release, significantly enhance macrophage efferocytosis, suppress inflammatory signaling, and accelerate wound repair in diabetic models. Thus, our engineered, sprayable, and adhesive microcarrier platform offers a stable, minimally invasive, and clinically adaptable strategy for advancing stem cell-derived exosome therapies in chronic diabetic wound repair.