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感染仍然是骨科手术的祸根。 尽管初次全关节置换术 (TJR) 后的感染发生率较低 (~1%)，但再次感染 比率非常高（15-40%），这导致了骨科范例认为金黄色葡萄球菌感染骨是 此外，众所周知，假体关节感染（PJI）是一种非随机事件，很大程度上是一种非随机事件。 为了解决这个问题，我们提出了最初的研究中心。 骨感染骨免疫学 (CoRTOBI) 的翻译检验以下假设：1) 是不受标准护理治疗影响的金黄色葡萄球菌储存库，2) 患者的免疫能力 针对金黄色葡萄球菌抗原的蛋白质组影响骨感染的发生率和结果。 已发表 33 篇出版物，6 项专利技术正在被行业转化为临床 合作伙伴以及一些仍然是本次更新的焦点的开创性发现，其中包括：1) 金黄色葡萄球菌。 活骨骨细胞腔隙小管网络 (OLCN) 的定植，2) 新型抗生素佐剂 专门针对这些可以 3D 打印到定制垫片中的机制，3) 定制多重 免疫测定法阐明金黄色葡萄球菌的免疫蛋白质组，4) 体内成像以量化“竞争” 实时识别植入物的“表面”，以及 5) 将抗 IsdB 反应识别为易受影响的免疫与抗 Gmd 反应作为小鼠和患者的保护性免疫，培养证实了金黄色葡萄球菌骨感染。 在本次更新中，管理核心将为 CoRTOBI 提供运营和财务管理。 还支持临床研究和生物统计需求，促进沟通，运行浓缩 计划，并维持试点和可行性项目计划（PFPP）。 行政核心是： 目标 1. 管理整个 CoRTOBI，其中包括人员管理、 通过定期评估对服务和研究进展进行财务监督和质量控制 目标 2. 促进 CoRTOBI 项目和核心研究人员、IAC 和 EAC、我们的会议之间的沟通。 NIH 资助的 CTSA、NIH/NIAMS 计划工作人员和更大的科学界 目标 3. 协调成本。 目标 4. 保持我们成功的试点和可行性项目计划。 (PFPP) 骨感染领域的目标 5. 获得新知识产权专利并与行业合作伙伴合作。 并且，目标 6. 为 CoRTOBI 研究人员、骨感染研究人员提供丰富的机会， 整形外科医生以及更大的科学界和非专业界人士。 CoRTOBI，我们将：1）阐明金黄色葡萄球菌在骨中定植的新机制，2）确定新的机制 抗生素佐剂，并展示它们在 3D 打印垫片中用于 1 阶段修复的用途，3) 定义了 易感免疫蛋白质组发生机制，并开发 mRNA 纳米颗粒疫苗来克服 4) 生成了一个综合算法来预测感染和临床结果。