Department of Orthopedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, Guangdong Provincial Engineering Research Center for Biomedical Engineering, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China.
Department of Orthopedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, Guangdong Provincial Engineering Research Center for Biomedical Engineering, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China.
Biomaterials. 2025 Feb;313:122762. doi: 10.1016/j.biomaterials.2024.122762. Epub 2024 Aug 17.
Osteomyelitis is an osseous infectious disease that primarily affects children and the elderly with high morbidity and recurrence. The conventional treatments of osteomyelitis contain long-term and high-dose systemic antibiotics with debridements, which are not effective and lead to antibiotic resistance with serious side/adverse effects in many cases. Hence, developing novel antibiotic-free interventions against osteomyelitis (especially antibiotic-resistant bacterial infection) is urgent and anticipated. Here, a bone mesenchymal stem cell membrane-constructed nanocell (CFE@CM) was fabricated against osteomyelitis with the characteristics of acid-responsiveness, hydrogen peroxide self-supplying, enhanced chemodynamic therapeutic efficacy, bone marrow targeting and cuproptosis induction. Notably, mRNA sequencing was applied to unveil the underlying biological mechanisms and found that the biological processes related to copper ion binding, oxidative phosphorylation, peptide biosynthesis and metabolism, etc., were disturbed by CFE@CM in bacteria. This work provided an innovative antibiotic-free strategy against osteomyelitis through copper-enhanced Fenton reaction and distinct cuproptosis, promising to complement the current insufficient therapeutic regimen in clinic.
骨髓炎是一种骨感染性疾病，主要影响儿童和老年人，发病率和复发率高。骨髓炎的传统治疗方法包括长期和大剂量的全身抗生素联合清创术，但这些方法效果不佳，且在许多情况下会导致抗生素耐药性和严重的副作用/不良反应。因此，迫切需要开发针对骨髓炎（尤其是对抗生素耐药菌感染）的新型无抗生素干预措施。在这里，我们构建了一种具有酸响应性、过氧化氢自供给、增强化学动力学治疗效果、骨髓靶向和铜死亡诱导作用的骨间充质干细胞膜构建纳米细胞（CFE@CM）来对抗骨髓炎。值得注意的是，我们应用 mRNA 测序揭示了其潜在的生物学机制，并发现 CFE@CM 可扰乱细菌中与铜离子结合、氧化磷酸化、肽生物合成和代谢等相关的生物学过程。这项工作通过铜增强的芬顿反应和独特的铜死亡提供了一种针对骨髓炎的创新无抗生素策略，有望补充临床治疗方案的不足。
