Administrative Core

行政核心

• 批准号: 10402964
• 负责人: Edward M. Schwarz
• 金额: $ 32.13万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10402964
• 关键词: 3D Print; Acceleration; Address; Adjuvant; Advisory Committees; Algorithms; Antibiotic Therapy; Antibiotics; Antigens; Award; Biochemistry; Biocompatible Materials; Biology; Biomechanics; Biometry; Clinic; Clinical; Clinical Research; Communicable Diseases; Communication; Communities; Community Outreach; Consensus; Custom; Diagnosis; Educational workshop; Evaluation; Event; Fostering; Funding; Genetic; Goals; Histology; Human Resources; Immune; Immunity; Immunoassay; Immunology; Immunosuppression; Implant; Incidence; Infection; Intellectual Property; International; Joint Prosthesis; Legal patent; Licensing; Medicine; Messenger RNA; Mus; Musculoskeletal; National Institute of Arthritis and Musculoskeletal and Skin Diseases; ORALIT; Orthopedic Surgery; Orthopedics; Osteocytes; Osteomyelitis; Outcome; Pathogenesis; Pathology; Patients; Persons; Pilot Projects; Prevention; Prognosis; Proteome; Publications; Quality Control; Race; Replacement Arthroplasty; Research; Research Personnel; Resources; Running; Schedule; Seminal; Services; Small Business Innovation Research Grant; Staphylococcus aureus; Staphylococcus aureus infection; Structure; Surface; Surgeon; Technology; Testing; Time; Tissue Engineering; Tissue imaging; Translating; Translational Research; United States National Institutes of Health; Universities; Vaccines; Work; base; bone; commercialization; cortical bone; cost effective; demographics; drug discovery; imprint; improved; in vivo imaging; industry partner; ineffective therapies; joint infection; materials science; meetings; microbial; molecular imaging; multimodality; nanoparticle; novel; osteoimmunology; prevent; programs; ranpirnase; response; standard of care; success; virtual

Bone infection, primarily caused by Staphylococcus aureus, remains the bane of orthopaedic surgery. Although the incidence of infection following primary total joint replacement (TJR) is low (~1%), reinfection rates are very high (15-40%), which has led to the orthopaedic paradigm that S. aureus infection of bone is incurable. Additionally, prosthetic joint infection (PJI) is known to be a non-random event that is largely determined by patient-specific factors. To address this, we proposed the original Center of Research Translation on the Osteoimmunology of Bone Infection (CoRTOBI) to test the hypotheses that: 1) there are reservoirs of S. aureus that are not affected by standard of care treatments, and 2) the patient’s immune proteome against S. aureus antigens impacts the incidence and outcome of bone infection. Our work on this has resulted in 33 publications, 6 patented technologies that are being translated to the clinic by industry partners, and several seminal discoveries that remain the focus of this renewal. These, include: 1) S. aureus colonization of the osteocyte lacuno-canalicular network (OLCN) of live bone, 2) novel antibiotic adjuvants that specifically target these mechanisms that can be 3D-printed into custom spacers, 3) custom multiplex immunoassays to elucidate the immune proteome of S. aureus, 4) in vivo imaging to quantify “the race for the surface” of implants in real time, and 5) identification of anti-IsdB responses as susceptible immunity vs. anti- Gmd responses as protective immunity in mice and patients with culture confirmed S. aureus bone infection. In this renewal, the Administrative Core will provide operational and fiscal management of the CoRTOBI. It will also support clinical research and biostatistical needs, facilitate communications, run the Enrichment Programs, and maintain the Pilot and Feasibility Project Program (PFPP). The Specific Aims of the Administrative Core are to: Aim 1. Govern the entire CoRTOBI, which includes administration of personnel, financial oversight, and quality controls on services and research progress through evaluations at scheduled meetings. Aim 2. Foster communications between CoRTOBI Project & Core investigators, the IAC & EAC, our NIH-funded CTSAs, NIH/NIAMS Program staff, and the greater scientific community. Aim 3. Coordinate cost- effective access to the Research Cores. Aim 4. Maintain our successful Pilot and Feasibility Project Program (PFPP) in Bone Infection. Aim 5. Patent new intellectual property and collaborate with industry partners. And, Aim 6. Provide enrichment opportunities for CoRTOBI investigators, bone infection researchers, orthopaedic surgeons, and the larger scientific and lay communities. At the conclusion of this renewed P50 CoRTOBI, we will have: 1) elucidated novel mechanisms of S. aureus colonization of bone, 2) identified novel antibiotic adjuvants, and demonstrate their use in 3D-printing spacers for 1-stage revision, 3) defined the mechanism of susceptible immune proteome genesis, and develop mRNA nanoparticle vaccines to overcome it, and 4) generated a comprehensive algorithm to predict infection and clinical outcomes.

主要由金黄色葡萄球菌引起的骨骼感染仍然是骨科手术的祸根。 尽管主要总关节置换（TJR）后感染事件较低（〜1％），但还原 率很高（15-40％），这导致了骨链球菌感染的骨科范式 无法治愈。另外，已知假体关节感染（PJI）是一个非随机事件，在很大程度上是 由患者特异性因素决定。为了解决这个问题，我们提出了原始研究中心 关于骨感染的骨气免疫学（Cortobi）的翻译，以检验：1） 是不受护理标准治疗影响的金黄色葡萄球菌的水库，2）患者的免疫力 针对金黄色葡萄球菌抗原的蛋白质组会影响骨骼感染的入射和结果。我们在这方面的工作 已产生了33个出版物，这6种专利技术被行业转化为诊所 合作伙伴和几个第二次发现仍然是这种续约的重点。这些，包括：1）金黄色葡萄球菌 活骨的骨细胞lacanalicular网络（OLCN）的定殖，2）新型抗生素调节器 特别针对可以将3D打印到自定义垫片中的这些机制，3）自定义多路复用 免疫测定阐明金黄色葡萄球菌的免疫蛋白酶，4）体内成像以量化“ 实时的即将的表面”，以及5）将抗ISDB反应鉴定为敏感免疫与反抗性 GMD反应是小鼠和培养患者的保护性免疫，证实了金黄色葡萄球菌的骨骼感染。 在此续约中，行政核心将提供Cortobi的运营和财政管理。会 还支持临床研究和生物统计需求，促进通信，运行丰富 程序，并维护飞行员和可行性项目计划（PFPP）。特定目标 行政核心是：AIM 1。管理整个Cortobi，其中包括人员管理， 财务监督以及通过计划的评估对服务和研究进度的质量控制 会议。 AIM 2。Cortobi Project与核心调查员，IAC＆EAC之间的寄养通讯 NIH资助的CTSA，NIH/NIAMS计划人员和更大的科学界。目标3。协调成本 - 有效访问研究核心。目标4。维护我们成功的飞行员和可行性项目计划 （PFPP）在骨骼感染中。目标5。专利新知识产权并与行业合作伙伴合作。 以及AIM 6。为Cortobi研究人员，骨骼感染研究人员提供丰富机会， 骨科医生以及更大的科学和外行社区。在此更新的P50结束时 Cortobi，我们将有：1）阐明了金黄色葡萄球菌定植的新型机制，2）鉴定出新型 抗生素调节器，并证明它们在3D打印垫片中用于1阶段修订版，3）定义 易感免疫蛋白质组发生的机制，并开发mRNA纳米颗粒疫苗以克服 IT和4）生成了一种综合算法来预测感染和临床结果。