Limb Restoration Using a Novel Rat Model of Composite Bone and Muscle Injury

使用复合骨和肌肉损伤的新型大鼠模型进行肢体恢复

• 批准号: 8490490
• 负责人: Nick J Willett
• 金额: $ 5.22万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-27 至 2013-06-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8490490
• 关键词: Address; Animal Model; Autologous Transplantation; Biomechanics; Bone Regeneration; Cicatrix; Defect; Degenerative Disorder; Development; Educational process of instructing; Engineering; Engraftment; Excision; Fellowship; Foundations; Freezing; Gait; General Population; Grant; Growth Factor; Healed; Imaging Techniques; Impairment; Incidence; Infection; Injury; Ischemia; Laboratories; Lead; Limb structure; Manuscripts; Measures; Mentors; Metric; Modeling; Muscle; Musculoskeletal; Musculoskeletal Diseases; Nature; Operative Surgical Procedures; Orthopedics; Pain; Process; Qualifying; Rattus; Regenerative Medicine; Research; Research Personnel; Resolution; Rest; Societies; Source; Stimulus; Surgeon; Techniques; Technology; Testing; Therapeutic; Tissue Engineering; Tissues; Training; Trauma; Vascularization; Writing; bone; career; design; effective therapy; efficacy testing; experience; functional restoration; healing; improved; insight; muscle regeneration; muscle strength; musculoskeletal injury; novel; novel strategies; osteogenic; osteoprogenitor cell; regenerative; repaired; restoration; skills; soft tissue; tissue regeneration; treatment strategy; tumor

DESCRIPTION (provided by applicant): The research presented in this proposal has been designed to develop a platform from which I can build a foundation for a career as an independent investigator. The objective of this proposal is to develop a composite bone and muscle injury model which we will then use to test engraftment of novel constructs and the resultant tissue regeneration and limb function. It is hypothesized that bone regeneration will be impaired in the presence of injury to the surrounding muscle and that this impairment will be overcome using novel tissue engineered muscle constructs to promote both muscle and bone regeneration. The specific aims to address this hypothesis are: Specific Aim I - To develop a composite injury model in the rat and quantitatively investigate the effect of muscle injury on bone regeneration and restoration of limb function. Specific Aim II - To quantitatively analyze the functional contribution of novel muscle therapeutics and constructs to bone regeneration in a composite injury model. We will comprehensively and quantitatively characterize the functional deficit as a measure of gait and muscle strength along with revascularization and numerous bone regeneration metrics. This composite injury model will serve as a new model to test novel tissue engineered constructs and therapeutics for both muscle and bone to investigate bone regeneration in the presence of a muscle injury. Further understanding of the interaction between muscle and bone during the regenerative process will help lead to improved treatments. I have a successful record in developing novel animal models through collaborative projects and am therefore uniquely qualified to succeed in this project. In addition to the research component, this fellowship will give me the necessary skills to be a successful independent investigator. I will receive training in surgical techniques for new animal models, grant and manuscript writing, teaching and mentoring. The Guldberg laboratory is recognized internationally as a leader in the use of high resolution imaging techniques in the field of regenerative medicine and has produced numerous successful tenure track investigators. This will be an excellent training experience for me that will prepare me for the rest of my career.

描述（由申请人提供）：本提案中提出的研究旨在开发一个平台，我可以通过该平台为独立调查员的职业生涯奠定基础。该提案的目的是开发一种复合骨和肌肉损伤模型，然后我们将用它来测试新型结构的植入以及由此产生的组织再生和肢体功能。据推测，在周围肌肉受伤的情况下，骨再生将受到损害，并且可以使用新型组织工程肌肉结构来克服这种损害，以促进肌肉和骨再生。解决这一假设的具体目标是： 具体目标一——建立大鼠复合损伤模型，定量研究肌肉损伤对骨再生和肢体功能恢复的影响。具体目标 II - 定量分析新型肌肉疗法和结构对复合损伤模型中骨再生的功能贡献。我们将全面、定量地描述功能缺陷，作为步态和肌肉力量以及血运重建和众多骨再生指标的衡量标准。这种复合损伤模型将作为测试新型组织工程结构和肌肉和骨骼疗法的新模型，以研究肌肉损伤情况下的骨再生。进一步了解再生过程中肌肉和骨骼之间的相互作用将有助于改进治疗方法。我在通过合作项目开发新型动物模型方面拥有成功的记录，因此我具有在该项目中取得成功的独特资格。除了研究部分之外，该奖学金还将赋予我成为一名成功的独立调查员所需的技能。我将接受新动物模型手术技术、资助和手稿写作、教学和指导方面的培训。古德伯格实验室被国际公认为再生医学领域高分辨率成像技术应用的领导者，并培养了众多成功的终身教授研究员。这对我来说将是一次极好的培训经历，为我余下的职业生涯做好准备。

项目成果

Attenuated human bone morphogenetic protein-2-mediated bone regeneration in a rat model of composite bone and muscle injury.

在复合骨和肌肉损伤的大鼠模型中，人骨形态发生蛋白 2 介导的骨再生减弱。

• 发表时间: 2013-04
• 作者: Willett, Nick J;Li, Mon;Uhrig, Brent A;Boerckel, Joel David;Huebsch, Nathaniel;Lundgren, Taran L;Warren, Gordon L;Guldberg, Robert E
• 通讯作者: Guldberg, Robert E