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

用于抗生素、细胞和生长工厂交付的承载 3D 打印植入物

• 批准号: 8704532
• 负责人: Leigh Ayres
• 金额: $ 8.33万
• 依托单位: OXFORD PERFORMANCE MATERIALS, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-12 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8704532
• 关键词: 3D Print; Animal Model; Antibiotics; Applied Research; Area; Arthroplasty; Biocompatible Materials; Biological Assay; Biomedical Engineering; Blood Circulation; Chemical Engineering; Chronic; Clinical; Communicable Diseases; Data; Development; Devices; Diagnostic radiologic examination; Distal; Dose; Drug Delivery Systems; Engineering; Enzyme-Linked Immunosorbent Assay; Experimental Implants; FDA approved; Femur; Fracture; Future; General Hospitals; Geometry; Goals; Growth Factor; Health; Health Care Costs; Hip region structure; Histology; Hour; Implant; Infection; Joints; Knee; Knowledge; Letters; Liquid substance; Location; Maintenance; Massachusetts; Methods; Mission; Morphology; Orthopedic Surgery procedures; Orthopedics; Oryctolagus cuniculus; Osteomyelitis; Outcome; Patients; Performance; Perfusion; Pilot Projects; Polymers; Polymethyl Methacrylate; Process; Prosthesis; Public Health; Recovery; Replacement Arthroplasty; Research; Retrieval; Saline; Sampling; Schools; Science; Scientist; Staging; Surgeon; System; Technology; Time; Tissues; Titania; Titanium; Translating; Trauma; Universities; Validation; Vancomycin; Vertebral column; Weight-Bearing state; Work; bacterial resistance; base; bone; cell growth; cost; density; design; engineering design; flexibility; implantable device; improved; innovation; medical schools; meetings; mortality; multidisciplinary; new technology; novel strategies; response; retinal rods; simulation; spine bone structure; standard of care; success

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.

描述（由申请人提供）：该提案的目的是改善人造臀部和膝盖和其他植入设备的感染的治疗方法。这项多学科的建议涉及从马萨诸塞州骨科部（MGH），哈佛医学院以及哈佛大学的工程学院和应用科学学院的骨科部门的骨科手术，化学工程，流体动力学和生物医学工程领域建立的生产专家。在此提案中，将评估一种可以从根本上改变与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，以减少根除围场感染所需的治疗时间。应用程序中的特定目标是验证一种灌注载荷3D打印的PEKK聚合物，用于以高植入剂剂量以高植入剂剂量的局部递送。为了实现这一目标，将包含用于输送流体的通道的3D打印聚合物杆植入已接种金黄色葡萄球菌的兔子的股骨。将确定髓管，关节空间和全身循环中的万古霉素浓度以及感染的存在或不存在。万古霉素的水平将由基于ELISA的测定法确定。骨形态，组织反应和感染状态的变化将取决于射线照相，组织学和微生物培养。中心假设是，局部抗生素向植入物周围空间递送可以在短时间内消除已建立的感染。拟议的试点研究的理由是，灌注可以更广泛地使用 与PMMA的ABX洗脱相比，ABX和对局部ABX浓度的控制大大改善了。这些进步可以将TJI的治疗时间从数月减少到几周。 AIM 1的结果将是一个载荷膝关节垫片，能够在植入物周围空间（髓管和关节空间）中维持高水平的万古霉素。 AIM 2的结果将证明 可以通过灌注万古霉素来消除感染的股棒。 AIM 3的结果将证明可以通过灌注万古霉素来消除感染的载荷膝盖垫片。拟议的研究具有创新性，因为它结合了含负载的植入物材料与灌注药物输送系统的简单性和灵活性相结合。拟议的研究很重要，因为感染是一个负担重大的临床问题，导致患者长期遭受痛苦，死亡率增加，预计到2015年，损失了120亿美元/年。这项研究的影响是有可能快速提高骨骼和关节感染的治疗，减少医疗保健成本并减少患者的痛苦。