Small Scale Robotics for Automated Dental Biofilm Theranostics

用于自动化牙科生物膜治疗的小型机器人

• 批准号: 10658028
• 负责人: Hyun Koo
• 金额: $ 63.21万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-22 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658028
• 关键词: 3-Dimensional; 3D Print; Anatomy; Apical; Area; Biological; Cell Survival; Clinical; Collection; Complex; Coupled; Data; Dental; Detection; Development; Devices; Diagnosis; Diagnostic; Disinfection; Drug Delivery Systems; Electromagnetics; Endodontics; Ensure; Excision; Family suidae; Foundations; Future; Geometry; Human; In Situ; Infection; Irrigation; Jaw; Licensing; Location; Magnetism; Mammalian Cell; Manuals; Mechanics; Medicine; Methods; Microbial Biofilms; Modality; Modeling; Molds; Morphology; Motion; Movement; Nanotechnology; Needles; Oral; Oral cavity; Outcome; Performance; Peroxidases; Pharmaceutical Preparations; Polymers; Pre-Clinical Model; Procedures; Property; Pulp Canals; Retrieval; Robot; Robotics; Sampling; Shapes; Site; Small Business Innovation Research Grant; Structure; System; Technology; Testing; Therapeutic; Tooth structure; Ultrasonics; Visualization; antimicrobial; bactericide; clinical application; commercialization; conventional therapy; cost; cytotoxicity; dental biofilm; design; efficacy study; efficacy testing; follow-up; improved; in vivo; iron oxide nanoparticle; magnetic field; microrobot; nanoparticle; new technology; novel strategies; oral biofilm; particle; periapical; polymicrobial biofilm; prototype; response; robotic device; robotic system; soft tissue; stem cells; theranostics; tongue papilla; treatment optimization

PROJECT ABSTRACT Oral biofilm-related infections remain a persistent and costly clinical problem. Existing treatments are unable to simultaneously kill and physically disrupt biofilms and require manual biofilm removal procedures that are cumbersome with reduced efficacy in difficult to reach areas such as endodontic canal systems. Furthermore, options for sample retrieval for diagnostics during clinical procedures are limited. Efficacious, automated technologies capable of precisely targeting complex anatomical areas are needed to retrieve samples, kill and remove biofilms, and deliver drugs on site. We propose a novel approach combining nanotechnology and robotics to develop the first automated system for targeted disinfection, removal, and sampling of endodontic biofilms. We have designed small-scale robots using catalytic nanoparticles as building blocks that display tether-free controlled motion with multifunctionality. Our approach utilizes iron oxide nanoparticles (IONPs) with dual catalytic-magnetic properties that (i) generate bactericidal and biofilm degrading reactive molecules in situ, and (ii) remove the disrupted biofilm via magnetic-field driven robotic assemblies termed Catalytic Antibiofilm Robots (CARs). Preliminary data demonstrate that CARs locally remove and collect biofilms with high precision and efficacy in comparison to conventional treatment, including confined endodontic spaces. By tuning the magneto-catalytic properties and control of the CARs systems, we will develop robotic device prototypes that fit the oral cavity for simultaneous endodontic biofilm treatment, removal and sample retrieval. We propose to further improve IONP-made robots coupled with a clinical electromagnetic controller to develop two CARs-based oral biodevice platforms. (Aim 1) CAR1s, formed from aggregated IONP, will be used for catalytic bacterial killing, biofilm treatment, and sample retrieval from root canals for diagnostic analysis. We will identify key parameters for CAR1s improvement, assessing magnetic control, bioactivity and visualization/tracking. CAR1s will be evaluated for targeting difficult-to-reach areas, such as C-shaped/curved canals and isthmus, as well as treating and retrieving biofilms. We will characterize and improve CAR1 control first using 3D-printed tooth replicas with diverse canal morphologies to improve movement and controllability, followed by testing our system using ex vivo extracted tooth/typodont and pig jaw models. (Aim 2) CAR2s will be fabricated by 3D micromolding functional polymers with embedded IONPs for biofilm disruption, retrieval, and drug delivery at the apical region. We will optimize magnetic control and tracking, antibiofilm activity and triggered cargo delivery, testing efficacy to remove and retrieve biofilms. We will assess bioactivity using mixed- species biofilms and maneuverability to the apical region of the root canal recapitulated in 3D-printed teeth and ex vivo models, while rigorously evaluating the robotic device in geometries suited to the oral cavity with comparisons against conventional treatment. We expect the outcomes of the proposed studies will lead to the first robotic biodevice system developed for automated biofilm theranostics for applications in dental medicine.

项目摘要 口腔生物膜相关的感染仍然是一个持续的和昂贵的临床问题。现有的治疗方法无法 同时杀死和物理破坏生物膜，并需要手动生物膜去除程序， 在诸如牙髓管系统的难以到达的区域中麻烦且功效降低。此外，委员会认为， 在临床程序期间用于诊断的样本取回的选择是有限的。高效、自动化 需要能够精确靶向复杂解剖区域的技术来取回样本、杀死 去除生物膜，并在现场给药我们提出了一种结合纳米技术和 机器人技术开发第一个自动化系统，用于有针对性的消毒，去除和根管采样 生物膜我们已经设计了小型机器人，使用催化纳米颗粒作为构建模块， 具有多功能的无系绳控制运动。我们的方法利用氧化铁纳米颗粒（IONP）， 双重催化-磁性性质，（i）原位产生杀菌和生物膜降解反应分子， 和（ii）通过被称为催化抗生物膜的磁场驱动的机器人组件去除被破坏的生物膜 机器人（汽车）。初步数据表明，汽车以高精度局部去除和收集生物膜 和有效性，包括封闭的牙髓间隙。通过调谐 磁催化性能和控制的汽车系统，我们将开发机器人设备 适合口腔同时进行牙髓生物膜处理、去除和取样的原型 检索我们建议进一步改进IONP制造的机器人与临床电磁控制器相结合 开发两个基于CAR的口腔生物设备平台。(Aim 1）由聚集的IONP形成的CAR 1将被 用于催化细菌杀灭、生物膜处理和从根管中取出样本进行诊断分析。 我们将确定CAR 1 s改进的关键参数，评估磁控制，生物活性和 可视化/跟踪。将评价CAR 1靶向难以到达的区域，如C形/弯曲 运河和峡部，以及处理和回收生物膜。我们将表征和改善CAR 1控制 首先使用具有不同根管形态的3D打印牙齿复制品来改善运动和可控性， 然后使用离体提取的牙齿/印齿和猪颌模型测试我们的系统。(Aim（2）CAR 2将 通过3D微成型功能聚合物与嵌入的IONP制造，用于生物膜破坏，恢复， 以及在顶端区域的药物递送。我们将优化磁控制和跟踪，磁膜活动， 触发货物运送，测试去除和回收生物膜的功效。我们将使用混合- 3D打印牙齿中重现的根管根尖区的物种生物膜和可操作性， 离体模型，同时严格评估适合口腔的几何形状的机器人装置， 与常规治疗的比较。我们预计拟议研究的结果将导致 第一个机器人生物设备系统，用于牙科医学中的自动生物膜治疗诊断。