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.

项目概要 候选人：Hast 博士获得了机械工程学士学位，主修热力学 和博士学位。机械工程专业，重点是计算生物力学。他的长期目标是 成为一名独立研究人员，专注于改善脆性骨折后患者的治疗结果。这 该提案采用跨学科研究框架，利用小动物模型来确定以下机制： 控制健康和患病骨骼的骨折愈合。该提案的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必要的培训，以充分 定义骨质疏松症环境中控制愈伤组织形成和骨重塑的机制。这将 为他提供成为脆性骨折修复领域思想领袖所需的工具。 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、实验室技术方面的指导，并提供职业发展培训。博士。博尔克尔 和秦将作为联合导师，提供小动物手术、组织学、 免疫组织化学和分子分析。哈斯特博士还将设有咨询委员会（技术：刘博士， 安，梅塔，马诺加兰；职业：博士。索斯洛夫斯基、阿博加斯特、埃利奥特）指导他的发展。哈斯特博士将 定期参加教师会议、研讨会、讲习班和课程作业，使他成为一个完整和 独立研究员。他将在全国会议和同行评审期刊上展示他的研究成果。 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，设备齐全，可用于拟议的研究 培训和研究计划。 PCMD 并主持多项 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 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当前使用金属植入物进行愈合的临床范例 骨折。中心假设是，在适当的时机逐渐（基于梯度）增加负载将导致 改进模拟骨折的修复。为了检验这一新假设，将使用大鼠模型来实现两个目标。目标1 将确定逐步引入力传导对健康骨骼骨折修复的影响。目的 2 将确定需要对机械转导进行哪些改变来改善受损的骨折修复 骨。测试这些目标将为后续 R01（包括更大的动物）生成重要的初步数据 模型，以及可以加速和改善修复的药物干预措施。 对候选人的机构承诺：哈斯特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。