Abstract：
Wound healing is a dynamic process involving the timely transition of organized phases. However, infected wounds often experience prolonged inflammation due to microbial overload. Thus, addressing the viable treatment needs across different healing stages is a critical challenge in wound management. Herein, a novel core-shell microneedle (CSMN) patch is designed for the sequential delivery of tannic acid-magnesium (TA-Mg) complexes and extracellular vesicles from Lactobacillus druckerii (LDEVs). Upon application to infected sites, CSMN@TA-Mg/LDEV releases TA-Mg first to counteract pathogenic overload and reduce reactive oxygen species (ROS), aiding the transition to proliferative phase. Subsequently, the sustained release of LDEVs enhances the activities of keratinocytes and fibroblasts, promotes vascularization, and modulates the collagen deposition. Notably, dynamic track of microbial composition demonstrates that CSMN@TA-Mg/LDEV can both inhibit the aggressive pathogen and increase the microbial diversity at wound sites. Functional analysis further highlights the potential of CSMN@TA-Mg/LDEV in facilitating wound healing and skin barrier restoration. Moreover, it is confirmed that CSMN@TA-Mg/LDEV can accelerate wound closure and improve post-recovery skin quality in the murine infected wound. Conclusively, this innovative CSMN patch offers a rapid and high-quality alternative treatment for infected wounds and emphasizes the significance of microbial homeostasis.
摘要：
伤口愈合是一个动态过程，涉及组织阶段的及时过渡。然而,感染的伤口通常会由于微生物超负荷而经历长时间的炎症。因此，解决不同愈合阶段的可行治疗需求是伤口管理的关键挑战。在这里，设计了一种新型的核-壳微针（CSMN）贴片，用于从德氏乳杆菌（LDEV）连续递送单宁酸-镁（TA-Mg）复合物和细胞外囊泡。一旦申请到受感染的网站，CSMN@TA-Mg/LDEV首先释放TA-Mg以抵消致病性超负荷并减少活性氧（ROS），帮助过渡到增殖阶段。随后，LDEV的持续释放增强角质形成细胞和成纤维细胞的活性，促进血管化，并调节胶原沉积。值得注意的是,微生物组成的动态跟踪表明，CSMN@TA-Mg/LDEV既可以抑制侵袭性病原体，又可以增加伤口部位的微生物多样性。功能分析进一步强调了CSMN@TA-Mg/LDEV促进伤口愈合和皮肤屏障恢复的潜力。此外，证实CSMN@TA-Mg/LDEV可以加速伤口闭合并改善鼠类感染伤口的恢复后皮肤质量。最后，这种创新的CSMN贴片为感染伤口提供了一种快速和高质量的替代治疗方法，并强调了微生物稳态的重要性。
