Honglei Wang, Zibei Wu, Chen Gao, Wenhao Wang, Minglong Chen, Lin Yuan, Jiating Wang, Cairong Xiao, Yang Zhou, Fan Tong, Hanmei Li, Huile Gao, Xiang Gao, Jintao Fu. Probiotic living microneedles designed by interbacterial competition for accelerated infected wound healingJ. Acta Pharmaceutica Sinica B, 2025, 15(12): 6571-6586. DOI: 10.1016/j.apsb.2025.10.029
Citation: Honglei Wang, Zibei Wu, Chen Gao, Wenhao Wang, Minglong Chen, Lin Yuan, Jiating Wang, Cairong Xiao, Yang Zhou, Fan Tong, Hanmei Li, Huile Gao, Xiang Gao, Jintao Fu. Probiotic living microneedles designed by interbacterial competition for accelerated infected wound healingJ. Acta Pharmaceutica Sinica B, 2025, 15(12): 6571-6586. DOI: 10.1016/j.apsb.2025.10.029

Probiotic living microneedles designed by interbacterial competition for accelerated infected wound healing

  • Probiotic therapy offers a promising strategy for chronic infected wound management through pathogen suppression and immune modulation. However, its efficacy remains restricted by weak competitiveness in pathogen-rich niches and poor penetration across biofilm barriers. Inspired by bacterial competitive interactions, we developed a multifunctional microneedle (MN) platform to overcome these limitations. Lactobacillus reuteri (Lr) was coated with poly-l-lysine-modified metal–phenolic networks (MPNs) encapsulating doxorubicin (DOX), yielding DOX@MPN–PLL@Lr (DMP@Lr). The engineered probiotics were incorporated into dissolving MNs enriched with nutrient broth to ensure excellent microneedle performance and probiotic function. This design leverages MPN multifunctionality to reduce early-stage pathogenic burden via photothermal-assisted bacterial killing and near-infrared (NIR)-promoted antibiotic release, thereby enhancing probiotic competitiveness. Meanwhile, MNs physically disrupt biofilms for precise delivery into deep infection sites. In vitro, DMP@Lr achieved >99.9% (5.5 log) bactericidal efficiency, and its MNs exhibited a 1.4-fold higher biofilm clearance compared with blank MNs. In vivo, a single DMP@Lr MN patch promoted 93.9% wound closure, demonstrating potent antibacterial activity and accelerated healing. This study presents an innovative, translatable probiotic-based MN therapy for the effective treatment of chronically infected wounds.
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