Department of Biomedical Engineering, University of Stony Brook, Stony Brook, NY 11794, USA.
Institute for Surface Science and Corrosion, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
Acta Biomater. 2024 Nov;189:589-604. doi: 10.1016/j.actbio.2024.09.039. Epub 2024 Sep 27.
Implant-associated bacterial infections are a primary cause of complications in orthopedic implants, and localized drug delivery represents an effective mitigation strategy. Drawing inspiration from the morphology of desiccated soil, our group has developed an advanced drug-delivery system augmented onto titanium (Ti) plates. This system integrates zinc oxide (ZnO) nanorod arrays with a vancomycin drug layer along with a protective Poly(lactic-co-glycolic acid) (PLGA) coating. The binding between the ZnO nanorods and the drug results in attached drug blocks, isolated by desiccation-like cracks, which are then encapsulated by PLGA to enable sustained drug release. Additionally, the release of zinc ions and the generation of reactive oxygen species (ROS) from the ZnO nanorods enhance the antibacterial efficacy. The antibacterial properties of ZnO nanorod-drug-PLGA system have been validated through both in vitro and in vivo studies. Comprehensive investigations were conducted on the impact of bacterial infections on bone defect regeneration and the role of this drug-delivery system in the healing process. Furthermore, the local immune response was analyzed and the immunomodulatory function of the system was demonstrated. Overall, the findings underscore the superior performance of the ZnO nanorod-drug-PLGA system as an efficient and safe approach to combat implant-associated bacterial infections. STATEMENT OF SIGNIFICANCE: Implant-associated bacterial infections pose a significant clinical challenge, particularly in orthopedic procedures. To address this, we developed an innovative ZnO nanorod-drug-PLGA system for local antibiotic delivery on conventional titanium implants. This system is biodegradable and features a unique desiccation-like structure that enables sustained drug release, along with the active substances released from the ZnO nanorods. In a rat calvarial defect model challenged with S. aureus, our system demonstrated remarkable antibacterial efficacy, significantly enhanced bone defect regeneration, and exhibited local immunomodulatory effects that support both infection control and osteogenesis. These breakthrough findings highlight the substantial clinical potential of this novel drug delivery system and introduce a transformative coating strategy to enhance the functionality of traditional metallic biomaterials.
植入物相关的细菌感染是骨科植入物并发症的主要原因,局部药物输送是一种有效的缓解策略。受干燥土壤形态的启发,我们小组开发了一种在钛(Ti)板上增强的先进药物输送系统。该系统将氧化锌(ZnO)纳米棒阵列与万古霉素药物层以及保护性聚(乳酸-共-羟基乙酸)(PLGA)涂层结合在一起。ZnO 纳米棒与药物之间的结合导致附着的药物块通过类似干燥的裂缝分离,然后用 PLGA 包裹以实现药物的持续释放。此外,ZnO 纳米棒释放锌离子和产生活性氧(ROS)增强了抗菌效果。通过体外和体内研究验证了 ZnO 纳米棒-药物-PLGA 系统的抗菌性能。对细菌感染对骨缺损再生的影响以及该药物输送系统在愈合过程中的作用进行了综合研究。此外,还分析了局部免疫反应并证明了该系统的免疫调节功能。总的来说,这些发现强调了 ZnO 纳米棒-药物-PLGA 系统作为一种有效和安全的方法来对抗植入物相关细菌感染的优越性能。
植入物相关的细菌感染对临床治疗提出了重大挑战,特别是在骨科手术中。为了解决这个问题,我们开发了一种用于在传统钛植入物上局部输送抗生素的创新 ZnO 纳米棒-药物-PLGA 系统。该系统是可生物降解的,具有独特的类似干燥的结构,可实现持续的药物释放,以及 ZnO 纳米棒释放的活性物质。在金黄色葡萄球菌感染的大鼠颅骨缺损模型中,我们的系统表现出了显著的抗菌效果,极大地促进了骨缺损的再生,并表现出了局部免疫调节作用,这既支持了感染控制,也支持了成骨作用。这些突破性的发现突显了这种新型药物输送系统的巨大临床潜力,并提出了一种变革性的涂层策略,以增强传统金属生物材料的功能。