Modifying fragility fracture healing using a gradient-based mechanotransduction fixation approach

使用基于梯度的力传导固定方法改变脆性骨折愈合

• 批准号: 10301275
• 负责人: Michael William Hast
• 金额: $ 13.19万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10301275
• 关键词: 3D Print; Acute; Advisory Committees; American; Animal Model; Animals; Apoptosis; Bachelor' s Degree; Biocompatible Materials; Biological; Biological Assay; Biological Process; Biology; Biomechanics; Biomedical Engineering; Bone Diseases; Bone callus; Bone remodeling; Caring; Cells; Cellular Assay; Clinical; Complex; Custom; Data; Development; Devices; Disease; Doctor of Philosophy; Educational workshop; Engineering; Environment; Faculty; Failure; Femur; Foundations; Fracture; Fracture Healing; Funding; Future; Gene Expression; Glycolates; Goals; Grant; Healthcare; Histology; Home; Hybrids; Image; Immunohistochemistry; Implant; Injury; Interdisciplinary Study; Internal Fixators; Intervention; Journals; Knowledge; Laboratories; Laboratory Research; Learning; Longevity; Mechanics; Medical Imaging; Mentors; Metals; Mind; Mission; Modeling; Molecular; Molecular Profiling; Molecular and Cellular Biology; Musculoskeletal; Musculoskeletal Diseases; Operative Surgical Procedures; Orthopedics; Osteoclasts; Osteogenesis; Osteoporosis; Osteotomy; Ovariectomy; Patient-Focused Outcomes; Patients; Peer Review; Pennsylvania; Pharmacology; Positioning Attribute; Process; Radiation; Radiation induced damage; Rattus; Research; Research Assistant; Research Personnel; Role; Services; Site; Structure; Techniques; Testing; Thermodynamics; Time; TimeLine; Tissue Engineering; Training; Trauma; United States National Institutes of Health; Universities; Work; base; bone; bone healing; bone quality; career; career development; design; efficacy testing; follow-up; fragility fracture; healing; implant design; improved; insight; mechanical properties; mechanotransduction; meetings; metallicity; microCT; mortality; novel; osteoblast proliferation; osteoporosis with pathological fracture; osteoporotic bone; prevent; professor; repaired; sample fixation; symposium; tool

PROJECT SUMMARY Candidate: Dr. Hast received his bachelor's degree in mechanical engineering with a focus on thermodynamics and a Ph.D. in mechanical engineering with a focus on computational biomechanics. His long-term goal is to become an independent researcher focused on improving patient outcomes following fragility fractures. This proposal uses an interdisciplinary research framework using a small animal model to identify mechanisms that govern fracture healing in healthy and diseased bone. The objective of this proposal is to have Dr. Hast acquire the training necessary in small animal models, cellular assays, and molecular laboratory techniques to fully define the mechanisms that govern callus formation and bone remodeling in the milieu of osteoporosis. This will equip him with the tools necessary to become a thought leader in the field of fragility fracture repair. Mentoring Committee and Training Plan: Dr. Mauck will serve as primary mentor and provide structured mentoring in tissue engineering, laboratory techniques, and provide career development training. Drs. Boerckel and Qin will serve as co-mentors and provide hands-on training in small animal surgeries, histology, immunohistochemistry, and molecular profiling. Dr. Hast will also have advisory committees (technical: Drs. Liu, Ahn, Mehta, Manogharan; career: Drs. Soslowsky, Arbogast, Elliott) to guide his development. Dr. Hast will participate regularly in faculty meetings, seminars, workshops, and coursework to make him a complete and independent researcher. He will present his research at national conferences and in peer-reviewed journals. Environment: The University of Pennsylvania is home to the McKay Orthopaedic Research Laboratory and Penn Center for Musculoskeletal Disorders (PCMD), a 22,00 ft2 research space that is well-equipped for the proposed training and research plan. The PCMD and hosts several NIH supported core services focused on musculoskeletal research, which include histology, biomechanics, and imaging. Both the PCMD and Penn host weekly/monthly seminars in cellular and molecular biology, medical imaging, bioengineering, and professional development. Research: This proposed work will challenge the current clinical paradigms that use metal implants to heal fractures. The central hypothesis is that properly timed gradual (gradient-based) increases in loading will lead to improved repair of simulated fractures. To test this novel hypothesis, a rat model will be used in 2 aims. Aim 1 will establish the effects of gradual introduction of mechanotransduction on fracture repair in healthy bone. Aim 2 will determine what changes in mechanotransduction are required to improve fracture repair in compromised bone. Testing these aims will generate critical preliminary data for a follow-up R01 that includes a larger animal model, along with pharmacological interventions that may accelerate and improve repair. Institutional Commitment to Candidate: Dr. Hast is an Assistant Research Professor and has been provided start-up funds, laboratory space, and research personnel needed to perform the proposed work.

项目摘要 候选人：Hast博士获得了机械工程学士学位，重点是热力学 和博士学位在机械工程中，重点是计算生物力学。他的长期目标是 成为一名专注于改善脆弱性骨折后患者结局的独立研究人员。这 提案使用跨学科研究框架使用小动物模型来识别机制 控制健康和患病的骨骼骨折愈合。该提议的目的是让HAST博士获得 小动物模型，细胞测定和分子实验室技术中所必需的训练才能完全 定义在骨质疏松症环境中控制愈伤组织形成和骨骼重塑的机制。这会 为他配备成为脆弱裂缝维修领域的思想领导者所需的工具。 指导委员会和培训计划：Mauck博士将担任主要导师，并提供结构化的 指导组织工程，实验室技术，并提供职业发展培训。博士。 Boerckel QIN将担任联合官员，并提供小动物手术，组织学，组织学的动手培训 免疫组织化学和分子分析。 HAST博士还将成立咨询委员会（技术：Liu博士， Ahn，Mehta，Manogharan；职业：博士。 Soslowsky，Arbogast，Elliott）指导他的发展。 Hast Will博士 定期参加教师会议，研讨会，研讨会和课程，使他成为完整的 独立研究员。他将在国家会议和同行评审期刊上介绍他的研究。 环境：宾夕法尼亚大学是McKay骨科研究实验室和宾夕法尼亚大学的所在地 肌肉骨骼疾病中心（PCMD），这是一个22,00 FT2研究空间，适用于建议 培训和研究计划。 PCMD并托管了几项NIH支持的核心服务，重点关注 肌肉骨骼研究，包括组织学，生物力学和成像。 PCMD和Penn主机均 细胞和分子生物学，医学成像，生物工程和专业的每周/每月研讨会 发展。 研究：拟议的工作将挑战当前使用金属植入物治愈的临床范例 断裂。中心假设是，正确定时的渐进渐进（基于梯度）的负载增加将导致 改善了模拟裂缝的修复。为了检验这个新的假设，将在两个目标中使用大鼠模型。目标1 将建立机械转移对健康骨骼断裂修复的逐渐引入的影响。目的 2将确定需要哪些机械转移的变化以改善损坏的裂缝修复 骨。测试这些目标将为包括较大动物的后续R01生成关键的初步数据 模型，以及可以加速和改善维修的药理干预措施。 机构对候选人的承诺：HAST博士是助理研究教授，已被提供 启动资金，实验室空间和研究人员需要执行拟议的工作。