人工关节感染(PJI)是一种破坏性的并发症,需要手术干预和长期的抗菌治疗。PJI的患病率正在上升,在美国,每年平均发病率为60,000例,预计每年的费用为18.5亿美元。PJI的潜在发病机制涉及细菌生物膜的形成,保护病原体免受宿主免疫反应和抗生素的影响,很难根除这种感染。植入物上的生物膜还对机械刷洗/擦洗去除方法具有抗性。由于生物膜的去除目前只能通过替换假体来实现,旨在根除生物膜同时保留植入物的疗法将彻底改变PJIs的管理。为了解决植入物上与生物膜相关感染相关的严重并发症,我们开发了一种基于水凝胶纳米复合材料系统的组合疗法,含有d-氨基酸(d-AA)和金纳米棒,其可以在生理温度下被递送并从溶液转变为凝胶状态,用于d-AA的持续释放和感染部位的光活化热处理。使用这种两步方法利用近红外光激活的水凝胶纳米复合材料系统进行热处理,在使用d-AA最初中断后,我们能够在体外成功证明在三维打印的Ti-6Al-4V合金植入物上生长的成熟金黄色葡萄球菌生物膜的完全根除。使用细胞测定的组合,计算机辅助扫描电子显微镜分析,和生物膜基质的共聚焦显微镜成像,使用我们的联合治疗,我们可以显示100%的生物膜根除。相比之下,我们只能看到使用清创术根除了25%的生物膜,抗生素,和植入物保留方法。此外,我们的基于水凝胶纳米复合材料的治疗方法在临床环境中具有适应性,并且能够抵抗医疗植入物上生物膜带来的慢性感染。
Prosthetic joint infection (PJI) is a devastating complication requiring surgical intervention and prolonged antimicrobial treatment. The prevalence of PJI is on the rise, with an average incidence of 60,000 cases per year and a projected annual cost of $1.85 billion in the US. The underlying pathogenesis of PJI involves the formation of bacterial biofilms that protect the pathogen from the host immune response and antibiotics, making it difficult to eradicate such infections. Biofilms on implants are also resistant to mechanical brushing/scrubbing methods of removal. Since the removal of biofilms is currently only achievable by the replacement of the prosthesis, therapies aimed at eradicating biofilms while enabling retention of implants will revolutionize the management of PJIs. To address severe complications associated with biofilm-related infections on implants, we have developed a combination treatment that is based on a hydrogel nanocomposite system, containing d-amino acids (d-AAs) and gold nanorods, which can be delivered and transforms from a solution to a gel state at physiological temperature for sustained release of d-AAs and light-activated thermal treatment of infected sites. Using this two-step approach to utilize a near-infrared light-activated hydrogel nanocomposite system for thermal treatment, following initial disruption with d-AAs, we were able to successfully demonstrate in vitro the total eradication of mature Staphylococcus aureus biofilms grown on three-dimensional printed Ti-6Al-4V alloy implants. Using a combination of cell assays, computer-aided scanning electron microscopy analyses, and confocal microscopy imaging of the biofilm matrix, we could show 100% eradication of the biofilms using our combination treatment. In contrast, we were only able to see 25% eradication of the biofilms using the debridement, antibiotics, and implant retention method. Moreover, our hydrogel nanocomposite-based treatment approach is adaptable in the clinical setting and capable of combating chronic infections brought about by biofilms on medical implants.