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

描述(申请人提供)：这项提案的目标是改善人工髋关节和膝盖感染以及其他植入装置的治疗。这项多学科的建议涉及来自国防部的传染病、矫形外科、化学工程、流体动力学和生物医学工程方面的资深和富有成效的专家。马萨诸塞州总医院(MGH)、哈佛医学院和哈佛大学工程与应用科学学院的骨科博士。在这项提案中，将评估一种可能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。这项应用的特殊目标是验证一种可灌注承载3D打印PEKK聚合物，用于在植入物周围高剂量受控和持续的局部给药。为了实现这一目标，含有液体输送通道的3D打印聚合物棒将被植入接种了金黄色葡萄球菌的兔子的股骨。将测定髓管、关节间隙和体循环中的万古霉素浓度，以及是否有感染。万古霉素的水平将通过基于酶联免疫吸附试验的检测来确定。骨形态、组织反应和感染状态的变化将通过放射学、组织学和微生物培养来确定。中心假设是，将局部抗生素输送到种植体周围空间可以在短时间内根除既定的感染。拟议的先导性研究的基本原理是，灌流能够更广泛地使用 与从PMMA洗脱的ABX相比，ABX和大大改善了对局部ABX浓度的控制。这些进展可能会将TJI的治疗时间从几个月减少到几周。目标1的结果将是一种负重的膝关节间隔物，能够在种植体周间隙(髓管和关节间隙)维持高水平的万古霉素。目标2的结果将是验证 可通过灌流万古霉素根治感染的股骨棒。目标3的结果将验证负重膝关节间隔物可以通过灌流万古霉素来根除感染。这项拟议的研究具有创新性，因为它将承载植入材料与可灌注药物输送系统的简单和灵活结合在一起。这项拟议的研究意义重大，因为感染是一个沉重的临床问题，会导致患者长期痛苦、死亡率增加，预计到2015年每年将花费120亿美元。这项研究的影响是有可能迅速推进骨和关节感染的治疗，降低医疗成本，减少患者的痛苦。

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.