Biofilm Research Labs, Levy Center for Oral Health, Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, USA.
Solid-Biological Interface Group (SolBIN), Department of Physics, Universidade Federal do Ceará, Fortaleza-CE, Brazil.
Sci Robot. 2019 Apr 24;4(29). doi: 10.1126/scirobotics.aaw2388.
Magnetically driven robots can perform complex functions in biological settings with minimal destruction. However, robots designed to damage deleterious biostructures could also have important impact. In particular, there is an urgent need for new strategies to eradicate bacterial biofilms as we approach a post-antibiotic era. Biofilms are intractable and firmly attached structures ubiquitously associated with drug-resistant infections and destruction of surfaces. Existing treatments are inadequate to both kill and remove bacteria leading to reinfection. Here we design catalytic antimicrobial robots (CARs) that precisely and controllably kill, degrade and remove biofilms with remarkable efficiency. CARs exploit iron oxide nanoparticles (NPs) with dual catalytic-magnetic functionality that (i) generate bactericidal free radicals, (ii) breakdown the biofilm exopolysaccharide (EPS) matrix, and (iii) remove the fragmented biofilm debris via magnetic field driven robotic assemblies. We develop two distinct CAR platforms. The first platform, the biohybrid CAR, is formed from NPs and biofilm degradation products. After catalytic bacterial killing and EPS disruption, magnetic field gradients assemble NPs and the biodegraded products into a plow-like superstructure. When driven with an external magnetic field, the biohybrid CAR completely removes biomass in a controlled manner, preventing biofilm regrowth. Biohybrid CARs can be swept over broad swathes of surface or can be moved over well-defined paths for localized removal with microscale precision. The second platform, the 3D molded CAR, is a polymeric soft robot with embedded catalytic-magnetic NPs, formed in a customized 3D printed mold to perform specific tasks in enclosed domains. Vane-shaped CARs remove biofilms from curved walls of cylindrical tubes, and helicoid-shaped CARs drill through biofilm clogs, while simultaneously killing bacteria. In addition, we demonstrate applications of CARs to target highly confined anatomical surfaces in the interior of human teeth. These 'kill-degrade-and-remove' CARs systems could have significant impact in fighting persistent biofilm-infections and in mitigating biofouling of medical devices and diverse surfaces.
磁性驱动的机器人可以在最小破坏的情况下在生物环境中执行复杂的功能。然而,设计用于破坏有害生物结构的机器人也可能产生重要影响。特别是,在抗生素时代即将到来之际,我们迫切需要新的策略来根除细菌生物膜。生物膜是普遍存在的难以处理的牢固附着结构,与耐药性感染和表面破坏有关。现有的治疗方法不足以杀死和去除细菌,导致再次感染。在这里,我们设计了精确和可控的催化抗菌机器人 (CARs),以极高的效率杀死、降解和去除生物膜。CARs 利用具有双重催化-磁性功能的氧化铁纳米颗粒 (NPs),(i) 产生杀菌自由基,(ii) 破坏生物膜胞外多糖 (EPS) 基质,(iii) 通过磁场驱动的机器人组件去除碎片化的生物膜碎片。我们开发了两种不同的 CAR 平台。第一个平台,生物杂交 CAR,由 NPs 和生物膜降解产物组成。在催化细菌杀伤和 EPS 破坏后,磁场梯度将 NPs 和生物降解产物组装成犁状超结构。当用外部磁场驱动时,生物杂交 CAR 可以以受控的方式完全去除生物量,防止生物膜再生。生物杂交 CAR 可以在较宽的表面上扫荡,也可以在微尺度精度上沿明确定义的路径移动,用于局部去除。第二个平台,3D 成型 CAR,是一种具有嵌入式催化-磁性 NPs 的聚合物软机器人,由定制的 3D 打印模具形成,用于在封闭区域执行特定任务。叶片状 CAR 从圆柱形管的弯曲壁上去除生物膜,螺旋状 CAR 钻透生物膜堵塞物,同时杀死细菌。此外,我们还展示了 CAR 在靶向人类牙齿内部高度受限的解剖表面的应用。这些“杀灭-降解-去除”的 CAR 系统在对抗持久性生物膜感染和减轻医疗器械和各种表面的生物污垢方面可能具有重要影响。