School of Biomedical Engineering, The University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 5B9, Canada.
Bone and Joint Institute, The University of Western Ontario, The Sandy Kirkley Centre for Musculoskeletal Research, University Hospital B6-200, London, Ontario, N6G 2V4, Canada.
Adv Healthc Mater. 2023 Sep;12(22):e2202807. doi: 10.1002/adhm.202202807. Epub 2023 May 1.
Infection is a major complication associated with orthopedic implants. It often involves the development of biofilms on metal substrates, which act as barriers to the host's immune system and systemic antibiotic treatment. The current standard of treatment is revision surgery, often involving the delivery of antibiotics through incorporation into bone cements. However, these materials exhibit sub-optimal antibiotic release kinetics and revision surgeries have drawbacks of high cost and recovery time. Herein, a new approach is presented using induction heating of a metal substrate, combined with an antibiotic-loaded poly(ester amide) coating undergoing a glass transition just above physiological temperature to enable thermally triggered antibiotic release. At normal physiological temperature, the coating provides a rifampicin depot for >100 days, while heating of the coating accelerates drug release, with >20% release over a 1-h induction heating cycle. Induction heating or antibiotic-loaded coating alone each reduce Staphylococcus aureus (S. aureus) viability and biofilm formation on Ti, but the combination causes synergistic killing of S. aureus as measured by crystal violet staining, determination of bacterial viability (>99.9% reduction), and fluorescence microscopy of bacteria on surfaces. Overall, these materials provide a promising platform enabling externally triggered antibiotic release to prevent and/or treat bacterial colonization of implants.
感染是与骨科植入物相关的主要并发症。它通常涉及金属基质上生物膜的形成，生物膜作为宿主免疫系统和全身抗生素治疗的屏障。目前的标准治疗方法是翻修手术，通常涉及通过将抗生素掺入骨水泥中来递送抗生素。然而，这些材料表现出不理想的抗生素释放动力学，并且翻修手术具有成本高和恢复时间长的缺点。在此，提出了一种新方法，即使用金属基质的感应加热，结合负载抗生素的聚（酯酰胺）涂层，使其在略高于生理温度的玻璃化转变温度以上进行热触发抗生素释放。在正常生理温度下，该涂层提供了超过 100 天的利福平库，而涂层的加热加速了药物释放，在 1 小时感应加热循环中释放超过 20%。感应加热或负载抗生素的涂层本身都可以降低金黄色葡萄球菌（S. aureus）在 Ti 上的活力和生物膜形成，但组合使用会通过结晶紫染色、细菌活力测定（>99.9%减少）和细菌荧光显微镜观察表面来协同杀死 S. aureus。总体而言，这些材料提供了一个有前途的平台，能够实现外部触发的抗生素释放，以预防和/或治疗植入物的细菌定植。
