Data from: A resorbable antibiotic-eluting polymer composite bone void filler for perioperative infection prevention in a rabbit radial defect model

Nearly 1.3 million total joint replacement procedures are performed in the United States annually, with numbers projected to rise exponentially in the coming decades. Although finite infection rates for these procedures remain consistently low, device-related infections represent a significant cause of implant failure, requiring secondary or revision procedures. Revision procedures manifest several-fold higher infection recurrence rates. Importantly, many revision surgeries, infected or not, require bone void fillers to support the host bone and provide a sufficient tissue bed for new hardware placement. Antibiotic-eluting bone void fillers (ABVF), providing both osteoconductive and antimicrobial properties, represent one approach for reducing rates of orthopedic device-related infections. Using a solvent-free, molten-cast process, a polymer-controlled antibiotic-eluting calcium carbonate hydroxyapatite (HAP) ceramic composite BVF (ABVF) was fabricated, characterized, and evaluated in vivo using a bacterial challenge in a rabbit radial defect window model. ABVF loaded with tobramycin eliminated the infectious burden in rabbits challenged with a clinically relevant strain of Staphylococcus aureus (inoculum as high as 107 CFU). Histological, microbiological, and radiographic methods were used to detail the effects of ABVF on microbial challenge to host bone after 8 weeks in vivo. In contrast to the HAP/BVF controls, which provided no antibiotic protection and required euthanasia 3 weeks post-operatively, tobramycin-releasing ABVF animals showed no signs of infection (clinical, microbiological, or radiographic) when euthanized at the 8-week study endpoint. ABVF sites did exhibit fibrous encapsulation around the implant at 8 weeks. Local antibiotic release from ABVF to orthopedic sites requiring bone void fillers eliminated the periprosthetic bacterial challenge in this 8-week in vivo study, confirming previous in vitro results.

美国每年开展的全关节置换手术量近130万例，且预计未来数十年该数字将呈指数级增长。尽管此类手术的感染率始终处于较低区间，但与植入物相关的感染仍是导致植入失败的重要诱因，往往需要实施二次手术或翻修手术。翻修手术的感染复发率则高出数倍。尤为重要的是，无论是否存在感染，多数翻修手术都需要使用骨缺损填充材料来支撑宿主骨，并为新植入器械的置入提供足够的组织床。
抗生素洗脱型骨缺损填充材料（Antibiotic-eluting bone void fillers, ABVF）兼具骨传导性与抗菌性能，是降低骨科植入物相关感染发生率的有效途径之一。本研究采用无溶剂熔融浇铸工艺，制备了一种聚合物调控的抗生素洗脱型碳酸钙羟基磷灰石（Hydroxyapatite, HAP）陶瓷复合骨缺损填充材料（ABVF），并通过兔桡骨缺损窗细菌攻毒模型对其进行体内表征与评价。
负载妥布霉素的ABVF可清除接种临床致病株金黄色葡萄球菌（Staphylococcus aureus，接种量最高可达10^7菌落形成单位）的家兔体内的感染负荷。研究人员通过组织学、微生物学与影像学方法，详细分析了ABVF在体内植入8周后对宿主骨抵御微生物攻毒的影响。与未提供抗生素防护、需在术后3周实施安乐死的HAP/BVF对照组不同，释放妥布霉素的ABVF实验组家兔在8周研究终点处安乐死时，未表现出任何感染迹象（临床、微生物学及影像学层面均无感染表现）。在植入8周后，ABVF植入部位确实出现了植入物周围的纤维包膜形成现象。本项为期8周的体内研究表明，ABVF在骨科骨缺损填充部位的局部抗生素释放可消除假体周围的细菌感染负荷，验证了此前的体外实验结果。