近年来，全球耐药感染形势严峻，其中生物膜相关感染占比超过六成，已成为临床抗感染领域的重要难题之一。生物膜由细菌及其分泌的胞外聚合物组成，形成致密物理屏障，阻碍抗生素渗透；其内部乏氧、酸性微环境可抑制免疫细胞功能，损害局部组织修复。传统抗生素和手术清创难以彻底清除生物膜，且无法逆转感染后组织愈合不良的状态。因此，亟需兼具高效杀菌与组织修复功能的新型治疗策略。
针对上述挑战，我院兼职教授复旦大学附属华山医院运动医学科陈俊教授团队联合我院黄高山教授、梅永丰教授联合报道了一款时序响应型磁性微机器人体系(Microrobots-ZIF-8 System, MZ-8)。该微机器人以天然花粉为结构原型，表面修饰磁性纳米颗粒并采用原子层沉积技术诱导包覆沸石咪唑酯骨架涂层。其集仿生形貌、磁控驱动与生物膜微环境响应型锌离子（Zn2+）释药功能于一体。在外磁场引导下可在受限空间内实现集群式运动，并能在生物膜感染环境中触发Zn2+的释放以促进感染微环境的自修复通路表达。相关成果以研究论文在《美国科学院院刊》（Proceedings of the National Academy of Sciences of the United States of America）上发表，题为“Magnetically Actuated Microrobotic System for Sequential Treatment of Biofilm”。
图1：时序响应型磁性微机器人体系的设计与治疗生物膜的机制
该体系的作用机制遵循“先清除、后修复”的时序逻辑。在第一阶段，MZ-8集群可在自动化磁控系统驱动下于动物关节内实现集群式异步驱动，其仿生刺状表面对植入物表面的生物膜进行物理刮除，实现高效清除；同时，MZ-8的运动轨迹可被近红外二区（NIR-II）光学成像设备实时动态监测。
图2：MZ-8的在体监测驱动及靶向清除生物膜
在第二阶段，在特异的生物膜感染的酸性微环境中MZ-8也可以在清除感染灶后时序释放Zn2+，以驱动微环境中免疫修复通路干预实现免疫调控介导的组织修复。体内实验证实，MZ-8组骨再生、骨重塑效果突出。机制层面，MZ-8 释放的Zn2+可诱导巨噬细胞向M2修复表型极化，相关功能基因与信号通路被激活，核心基因形成调控网络，最终通过免疫调控实现高效组织修复。
图3：MZ-8通过免疫调控实现生物膜清除后的组织修复
为了进一步拓展MZ-8的临床应用前景，MZ-8被注射进人体骨关节环境并初步实现了临床X射线成像和磁场驱动下的精准导航和精准驱动。整套机器人系统兼顾治疗效果、操控性与安全性，为生物膜感染提供了影像引导式精准治疗新策略，为磁控微型机器人的临床转化开拓了巨大的应用前景。
图4：MZ-8在人体组织中的精准驱动
综上所述，该研究将物理破膜、磁控驱动与生物膜微环境响应释药集成于同一微型机器人系统，为生物膜感染提供了影像引导式精准治疗新策略。梅永丰教授、陈俊教授、黄高山教授、冯思嘉主治医师/副研究员为该论文共同通讯作者，复旦大学附属华山医院博士研究生李舜尧、我院梅宇博士以及复旦大学附属华山医院博士研究生许锴为论文共同第一作者，我院硕士研究生汪奕、赵时芸、本科生陈隅安参与了该项研究工作。该研究得到了国家自然科学基金，上海市市科委项目的资助和支持。
文章信息：
Shunyao Li, Yu Mei, Kai Xu, Huaixuan Sheng, Yu-an Chen, Mingda Teng, Bohan Xu, Bingqian Jiang, Chengxuan Yu, Huizhu Li, Shiyun Zhao, Yi Wang, Xiao Zhang, Yiyang Zhao, Yueming Wang, Yan Wo, Zhaochen Li, Siwen Shen, Yunxia Li, Min Tang, Yongfeng Mei, Jun Chen, Gaoshan Huang, Sijia Feng, Magnetically actuated microrobotic system for sequential treatment of biofilm, Proceedings of the National Academy of Sciences of the United States of America, 2026, 123(0), e2535216123.
文章链接：
www.pnas.org/doi/10.1073/pnas.2535216123
Magnetically Actuated Microrobotic System for Sequential Treatment of Biofilm
Biofilm-associated infections present a critical therapeutic challenge due to antibiotic resistance and impaired tissue healing. Here, we present a self-sequential microrobotic system (MZ-8) that integrates real-time human-steered navigation with autonomous, microenvironment-responsive therapy to actively eradicate biofilms and promote tissue regeneration. This interactive platform features a spine-inspired structure for mechanical biofilm disruption, a pH-responsive ZIF-8 coating for immunomodulatory Zn²⁺ release, and closed-loop actuation under second near-infrared (NIR-II) fluorescence guidance. In a rat model of periprosthetic joint infection, MZ-8 achieved effective biofilm removal (87.6% eradication), induced a pro-regenerative immune response by polarizing macrophages toward the M2 phenotype, and significantly enhanced tissue regeneration. Transcriptomic analysis further revealed the activation of immunomodulatory pathways and upregulation of M2-associated genes, confirming the system's self-sequential shift from eradication to repair. Moreover, validation in a rabbit model and human knee joint confirmed its operational feasibility under clinical imaging guidance and excellent biosafety. This work establishes that integrating physical eradication, biochemical immunomodulation, and interactive control within a single platform is essential for advancing from infection clearance to functional tissue restoration. Thus, it provides a new therapeutic paradigm for biofilm-associated diseases and lays a foundation for future intelligent, clinically adaptive anti-infective systems.
审核：黄高山、陈相仲