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首页> 外文期刊>European Cells & Materials >3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection
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3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection

机译：3D打印生物陶瓷用于双重抗生素输送，以治疗植入物相关的骨感染

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Surgical implant-associated bone infections (osteomyelitis) have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and locally to the affected site in poly (methyl methacrylate) (PMMA) bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally-deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerisation. To examine the efficacy of localised, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS) by three-dimensional (3D) printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50 % of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100 % of the bones treated with vancomycin monotherapy using PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics.
机译：与外科植入物相关的骨感染（骨髓炎）具有严重的临床和社会经济后果。慢性骨感染的治疗通常涉及在聚甲基丙烯酸甲酯（PMMA）骨水泥中全身和局部给予患处抗生素。考虑到影响生物膜中细菌所需的高抗生素浓度，局部递送对于在感染部位达到高剂量很重要。由于会干扰PMMA聚合，PMMA不适合局部递送某些生物膜特异性抗生素，包括利福平。为了检查与PMMA标准品相比局部联合抗生素给药的功效，我们通过三维（3D）打印制造了载有利福平和万古霉素的磷酸钙支架（CPS），以治疗与植入物相关的金黄色葡萄球菌骨感染小鼠模型。与载有万古霉素的PMMA相比，所有载有万古霉素和利福平的CPS治疗均可显着降低细菌负担。在接受持续释放万古霉素和利福平的CPS的小鼠中，有50％的小鼠的骨骼细菌培养阴性。相比之下，使用PMMA或CPS进行万古霉素单药治疗的骨骼中100％为培养阳性。然而，与PMMA相比，单一疗法CPS显着降低了修订后的细菌代谢负荷。生物膜仍保留在固定硬件上，但局部利福平递送明显减少了感染引起的骨破坏。这些数据表明，尽管具有挑战性的保留植入物的感染模型，但利福平和万古霉素从3D打印CPS共同递送（这是PMMA不可能实现的），显着改善了植入物相关性骨髓炎的疗效。但是，生物膜对固定硬件的持久性重申了植入物交换或其他生物膜根除策略以补充局部抗生素的重要性。

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