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: 10627912
• 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/10627912
• 关键词: 3D Print; Acceleration; 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; Cellular biology; Clinical; Complex; Custom; Data; Development; Devices; Disease; Doctor of Philosophy; Educational workshop; Engineering; Environment; Faculty; Failure; Femur; Fracture; Funding; Future; Gene Expression; Glycolates; Goals; Grant; Healthcare; Histology; Home; Hybrids; Image; Immunohistochemistry; Implant; Injury; Institution; Interdisciplinary Study; Internal Fixators; Intervention; Journals; Knowledge; Laboratories; Laboratory Research; Learning; Longevity; Mechanics; Medical Imaging; Mentors; Metals; Mind; Mission; Modeling; Molecular; Molecular Biology; Molecular Profiling; Motion; Musculoskeletal; Musculoskeletal Diseases; Operative Surgical Procedures; Orthopedics; Osteoclasts; Osteogenesis; Osteoporosis; Osteotomy; Ovariectomy; Patient-Focused Outcomes; Patients; Peer Review; Pennsylvania; Positioning Attribute; Process; Radiation; Radiation induced damage; Rattus; Research; Research Assistant; Research Personnel; Role; Services; Site; Structure; Techniques; Testing; Thermodynamics; Time; Tissue Engineering; Training; Trauma; United States National Institutes of Health; Universities; Work; bone; bone fracture repair; 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; pharmacologic; prevent; professor; repaired; sample fixation; skills; symposium; timeline; 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.

项目总结 候选人：哈斯特博士获得了机械工程学士学位，主修热力学 以及机械工程博士学位，专注于计算生物力学。他的长期目标是 成为一名独立研究人员，专注于改善脆性骨折后的患者预后。这 Proposal使用跨学科研究框架，使用小动物模型来确定 管理健康和患病骨骼的骨折愈合。这项提议目的是让哈斯特博士获得 小动物模型、细胞分析和分子实验室技术方面的必要培训，以充分 明确骨质疏松环境下骨痂形成和骨重建的机制。这将是 让他具备必要的工具，成为脆性骨折修复领域的思想领袖。 指导委员会和培训计划：Mauck博士将担任主要导师，并提供有组织的 指导组织工程、实验室技术，并提供职业发展培训。Boerckel博士 秦将担任共同导师，提供小动物手术、组织学、 免疫组织化学和分子图谱。Hast博士还将有咨询委员会(技术：刘博士， Ahn、Mehta、Manogharan；职业：Soslowsky博士、Arbogast博士、Elliott博士)指导他的发展。哈斯特博士会 定期参加教员会议、研讨会、研讨会和课程作业，使他成为一个完整和 独立研究人员。他将在国家会议和同行评议的期刊上发表他的研究成果。 环境：宾夕法尼亚大学是麦凯整形外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)，一个22，00平方英尺的研究空间，为建议的 培训和研究计划。PCMD和托管了NIH支持的几项核心服务，重点是 肌肉骨骼研究，包括组织学、生物力学和成像。PCMD和宾夕法尼亚大学的主机 每周/每月的细胞和分子生物学、医学成像、生物工程和专业研讨会 发展。 研究：这项拟议的工作将挑战目前使用金属植入物愈合的临床范例 骨折。中心假设是，适当的时机逐步(基于梯度)的负荷增加将导致 改进了模拟骨折的修复。为了验证这一新的假设，将在两个目标中使用一只老鼠模型。目标1 将建立逐步引入机械转导对健康骨骼骨折修复的影响。目标 2将确定需要在机械转导方面的哪些变化来改善受损的骨折修复 骨头。测试这些目标将为后续的R01产生关键的初步数据，其中包括一只更大的动物 模型，以及可能加速和改善修复的药物干预。 对候选人的机构承诺：Hast博士是一名助理研究教授，并已获得 执行拟议工作所需的启动资金、实验室空间和研究人员。