Load bearing 3D printed implants for antibiotic, cell and growth factory delivery

描述（由申请人提供）：本提案的目标是改善人工髋关节和膝关节以及其他植入装置感染的治疗。这项多学科提案涉及来自麻省总医院（MGH）骨科、哈佛医学院和哈佛大学工程与应用科学学院的传染病、整形外科、化学工程、流体动力学和生物医学工程等领域的知名专家。在本提案中，将评估一种可以从根本上改变设备相关感染治疗的新方法。这项工作的长期目标是开发改进的方法，以减少根除假体周围感染所需的治疗时间。该应用的特定目标是验证一种可渗透承载的3D打印PEKK聚合物，用于在种植体周围高剂量下控制和持续地局部递送抗生素。为了实现这一目标，3D打印的含有液体输送通道的聚合物棒将被植入接种了金黄色葡萄球菌的兔子的股骨中。测定万古霉素在髓管、关节间隙和体循环中的浓度以及有无感染。万古霉素的水平将通过ELISA法测定。骨形态、组织反应和感染状态的变化将通过x线摄影、组织学和微生物培养来确定。中心假设是局部抗生素递送到种植体周围空间可以在短时间内根除已建立的感染。提出初步研究的基本原理是灌注可以更广泛地使用

DESCRIPTION (provided by applicant): The goal of this proposal is to improve the treatment for infections of artificial hips and knees and other implanted devices. This multidisciplinary proposal involves established and productive experts in infectious disease, orthopaedic surgery, chemical engineering, fluid dynamics and biomedical engineering from the Dept. of Orthopaedics at the Massachusetts General Hospital (MGH), Harvard Medical School and the School of Engineering and Applied Sciences at Harvard University. In this proposal, a new approach that could fundamentally change the treatment of device related infections will be evaluated. The long term goal of this work is to develop improved methods to reduce the treatment time required for eradicating peri-prosthetic infections. The particular objectives in ths application are to validate a perfusible load bearing 3D printed PEKK polymer for the controlled and sustained local delivery of antibiotics at high peri-implant doses. To achieve this objective, 3D printed polymer rods containing channels for the delivery of fluids will be implanted into the femora of rabbits that have been inoculated with Staph Aureus. The vancomycin concentration in the medullary canal, joint space and systemic circulation will be determined as well as the presence or absence of infection. Levels of vancomycin will be determined by ELISA based assays. Changes in bone morphology, tissue response and infection status will be determined by radiography, histology and microbiological culture. The central hypothesis is that local antibiotic delivery to the peri-implant space can eradicate an established infection in a short period of time. The rationale for the proposed pilot study is that perfusion enables a broader use of ABx and greatly improved control of local ABx concentrations than ABx elution from PMMA. These advances could reduce treatment time for TJI from months to weeks. The result of Aim 1 will be a load bearing knee spacer capable of maintaining high levels of vancomycin in the peri-implant space (medullary canal and joint space). The result of Aim 2 will be validation that a femoral rod that can eradicate infection by perfusion of vancomycin. The result of Aim 3 will be validation that a load bearing knee spacer that can eradicate infection by perfusion of vancomycin. The proposed research is innovative because it combines load-bearing implantable materials with the simplicity and flexibility of a perfusible drug delivery system. The proposed research is significant because infection is a burdensome clinical issue that results in prolonged patient suffering, increased mortality and is expected to cost $12 billion USD/yr by 2015. The impact of this study is the potential to rapidly advance treatment for bone and joint infections, reduce healthcare costs and reduce patient suffering.