Pop Rocks-Inspired Bubble Driven Exosome Propulsion via Microneedles for Synergistic Wound Healing

Abstract

Chronic nonhealing wounds remain a critical clinical challenge due to persistent bacterial infection, tissue hypoxia, and impaired cellular regeneration. Herein, inspired by the “popping” mechanism of Pop Rocks candy, we developed a multifunctional microneedle (MN) patch (Exo/ONB-MN) that integrates antibacterial hyperbranched polymer (HBPLT), mesenchymal stem cell-derived exosomes (MSC-Exos), and oxygen nanobubbles (ONBs) into a single dissolvable platform. The HBPLT component provides potent broad-spectrum antibacterial activity through physical membrane disruption. Upon application, ONBs embedded in the needle bases explosively release oxygen, generating a directional pressure wave that actively propels exosomes from the needle tips deep into the wound bed—a mechanism termed bubble-driven exosome propulsion. Concurrently, oxygen release alleviates local hypoxia, enhancing exosome uptake and amplifying their proregenerative effects. In vitro studies demonstrated that the Exo/ONB-MN patch significantly promoted fibroblast proliferation and migration while achieving near-complete eradication of Staphylococcus aureus and Escherichia coli. In an S. aureus-infected full-thickness wound mouse model, the patch accelerated wound closure to nearly 100% within 14 days, promoted organized collagen deposition, reduced pro-inflammatory cytokine expression, and induced a phenotypic switch from M1 to M2 macrophages. This Pop Rocks-inspired platform addresses the key pathological barriers of chronic wounds—infection, hypoxia, and impaired healing—through a synergistic, all-in-one strategy, offering a promising and translatable approach for advanced wound management.