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

描述（由申请人提供）：本提案中提出的研究旨在为我作为独立研究者的职业生涯奠定基础。本提案的目的是开发一种复合骨和肌肉损伤模型，然后我们将使用该模型来测试新结构的植入以及由此产生的组织再生和肢体功能。假设骨再生将在周围肌肉损伤的情况下受损，这种损伤将通过使用新型组织工程肌肉结构来促进肌肉和骨再生来克服。具体目的：1 .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。具体目的II -定量分析新型肌肉疗法和结构对复合损伤模型骨再生的功能贡献。我们将全面和定量地描述功能缺陷，作为步态和肌肉力量的测量，以及血运重建和许多骨再生指标。这种复合损伤模型将作为一种新的模型，用于测试肌肉和骨骼的新型组织工程结构和治疗方法，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善治疗方法。我有通过合作项目开发新型动物模型的成功记录，因此我有独特的资格在这个项目中取得成功。除了研究的部分，这个奖学金将给我必要的技能，成为一个成功的独立调查员。我将接受新动物模型的外科技术培训，拨款和手稿写作，教学和指导。古尔伯格实验室是国际公认的再生医学领域使用高分辨率成像技术的领导者，并培养了许多成功的终身教职研究员。这对我来说将是一次很好的训练经历，为我以后的职业生涯做准备。

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.