Department of Orthopedics & Physical Rehabilitation , University of Massachusetts Medical School , Worcester , Massachusetts 01655 , United States.
ACS Appl Mater Interfaces. 2019 Aug 14;11(32):28641-28647. doi: 10.1021/acsami.9b07648. Epub 2019 Jul 30.
Orthopedic implant-associated bacterial infection presents a major health threat due to tendency for periprosthetic bacterial colonization/biofilm formation that protects bacteria from host immune response and conventional antibiotic treatment. Using surface-initiated atom transfer radical polymerization and copper-catalyzed azide-alkyne cycloaddition (CuAAC), alkynylated vancomycin is conjugated to azido-functionalized side chains of polymethacrylates grafted from Ti6Al4V. High-efficiency CuAAC across the substrate is confirmed by complete surface conversion of azides by X-ray photoelectron spectroscopy (XPS) and elemental mapping of changing characteristic elements. The vancomycin-modified surface (Ti-pVAN) significantly reduces in vitro adhesion and colonization of () a main bacterial pathogen responsible for periprosthetic infection and osteomyelitis, compared to untreated Ti6Al4V, supporting retained antibacterial properties of the covalently conjugated antibiotics. When the surface-modified intramedullary Ti-pVAN pins are inserted into mouse femoral canals infected by bioluminescent Xen29 , significantly reduced local bioluminescence along with mitigated blood markers for infection are detected compared to untreated Ti6Al4V pins over 21 days. Ti-pVAN pins retrieved after 21 days are confirmed with ∼20-fold reduction in adherent bacteria counts compared to untreated control, supporting the ability of surface-conjugated vancomycin in inhibiting periprosthetic adhesion and colonization.
骨科植入物相关细菌感染是一个主要的健康威胁,因为其存在于假体周围的细菌定植/生物膜形成倾向,使细菌能够免受宿主免疫反应和常规抗生素治疗的影响。通过表面引发原子转移自由基聚合和铜催化的叠氮化物-炔烃环加成(CuAAC),将炔基化万古霉素与接枝在 Ti6Al4V 上的聚甲基丙烯酸酯的叠氮功能侧链偶联。通过 X 射线光电子能谱(XPS)和特征元素变化的元素映射,完全转化叠氮化物,证实了高效的 CuAAC 可以跨基底进行。与未处理的 Ti6Al4V 相比,万古霉素修饰的表面(Ti-pVAN)显著降低了一种主要的细菌病原体( )在体外的黏附和定殖,该病原体是导致假体周围感染和骨髓炎的原因,这表明共价偶联抗生素保留了其抗菌性能。当将表面修饰的髓内 Ti-pVAN 销插入由生物发光 Xen29 感染的小鼠股骨管中时,与未处理的 Ti6Al4V 销相比,在 21 天内检测到局部生物发光明显减少,且感染的血液标志物也得到了缓解。在 21 天后回收的 Ti-pVAN 销与未处理的对照相比,附着细菌数量减少了约 20 倍,这支持了表面偶联万古霉素抑制假体周围细菌黏附和定植的能力。