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 口腔生物膜相关感染仍然是一个持续存在且代价高昂的临床问题。现有的治疗方法无法 同时杀死和物理破坏生物膜，需要手动去除生物膜程序 在难以到达的区域（例如牙髓管系统）中，操作繁琐且功效降低。此外， 在临床操作过程中用于诊断的样本检索选项是有限的。高效、自动化 需要能够精确瞄准复杂解剖区域的技术来检索样本、杀死和 去除生物膜，并在现场输送药物。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，用于牙髓的有针对性的消毒、去除和取样 生物膜。我们设计了使用催化纳米颗粒作为构建块的小型机器人，可以显示 具有多功能性的无系绳控制运动。我们的方法利用氧化铁纳米粒子（IONP） 双重催化磁性特性，（i）原位产生杀菌和生物膜降解反应分子， (ii) 通过磁场驱动的机器人组件（称为催化抗菌膜）去除破坏的生物膜 机器人（汽车）。初步数据表明，CAR 能够高精度地局部去除和收集生物膜 以及与传统治疗（包括有限的牙髓空间）相比的疗效。通过调整 CAR系统的磁催化特性和控制，我们将开发机器人设备 适合口腔的原型，可同时进行牙髓生物膜治疗、去除和取样 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的结合 开发两个基于 CAR 的口腔生物设备平台。 （目标 1）由聚集的 IONP 形成的 CAR1 将 用于催化细菌杀灭、生物膜处理以及从根管中取出样本进行诊断分析。 我们将确定 CAR1 改进的关键参数，评估磁控制、生物活性和 可视化/跟踪。 CAR1 将针对难以到达的区域（例如 C 形/弯曲区域）进行评估 运河和峡部，以及治疗和恢复生物膜。我们将表征并改进 CAR1 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/typodont 和猪颌模型测试我们的系统。 （目标 2）CAR2 将 由嵌入 IONP 的 3D 微成型功能聚合物制成，用于生物膜破坏、恢复、 和心尖区域的药物输送。我们将优化磁控制和跟踪、抗菌膜活性和 触发货物输送，测试去除和回收生物膜的功效。我们将使用混合评估生物活性 3D 打印牙齿中重现的物种生物膜和根管顶端区域的可操作性 离体模型，同时严格评估机器人设备的适合口腔的几何形状 与传统治疗的比较。我们预计拟议研究的结果将导致 第一个为牙科医学应用的自动生物膜治疗诊断而开发的机器人生物设备系统。