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 和博士机械工程专业，重点是计算生物力学。他的长期目标是 成为一名独立的研究人员，专注于改善脆性骨折后的患者结局。这 建议使用跨学科的研究框架，使用小动物模型来确定 控制健康和患病骨的骨折愈合。这个提议的目的是让哈斯特博士 在小动物模型、细胞分析和分子实验室技术方面进行必要的培训， 明确骨质疏松症中骨痂形成和骨重建的机制。这将 为他提供必要的工具，使他成为脆性骨折修复领域的思想领袖。 导师委员会和培训计划：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。Boerckel博士 和秦将担任共同导师，并提供小动物手术，组织学， 免疫组织化学和分子分析。Hast博士还将设有咨询委员会（技术：Liu博士， 安，梅塔，Manogharan;职业生涯：博士索斯洛夫斯基，阿博加斯特，埃利奥特），以指导他的发展。哈斯特博士会 定期参加教师会议，研讨会，研讨会和课程，使他成为一个完整的， 独立研究员。他将在全国性会议和同行评审期刊上发表他的研究。 环境：宾夕法尼亚大学是麦凯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），一个22，00平方英尺的研究空间，为拟议的 培训和研究计划。PCMD和托管几个NIH支持的核心服务，重点是 肌肉骨骼研究，包括组织学、生物力学和成像。PCMD和Penn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：这项拟议中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，适当定时的逐渐（基于梯度）增加负荷将导致 改善模拟骨折的修复。为了检验这一新假设，将在2个目标中使用大鼠模型。要求1 将建立逐步引入机械传导对健康骨中骨折修复的影响。目的 2将确定机械传导的哪些变化需要改善受损的骨折修复。 骨头测试这些目标将为后续R 01（包括较大动物）生成关键的初步数据 模型，沿着药物干预，可能加速和改善修复。 对候选人的机构承诺：Hast博士是助理研究教授，并已提供 开展拟议工作所需的启动资金、实验室空间和研究人员。