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: 8127178
• 负责人: Nick J Willett
• 金额: $ 4.94万
• 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/8127178
• 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. PUBLIC HEALTH RELEVANCE: The management of large bone defects caused by trauma, degenerative disease, or tumor resection remains one of the most challenging problems faced by orthopaedic surgeons. It is critical that we develop technologies that are practical and effective for repair of large multi-tissue defects. Current therapies are only effective when sufficient tissue is present and, even then, may lead to scar formation and limited restoration of function. The proposed research will thus benefit the general public by identifying effective treatment strategies for composite tissue injuries sustained via a broad range of traumatic incidences.

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，从中我可以为独立调查员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型结构的植入以及由此产生的组织再生和肢体功能。假设在周围肌肉损伤的情况下，骨再生将受损，并且使用新型组织工程化肌肉构建体来促进肌肉和骨再生将克服这种损伤。解决这一假设的具体目标是：具体目标I-在大鼠中建立复合损伤模型，并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-定量分析新型肌肉治疗剂和结构对复合损伤模型中骨再生的功能贡献。我们将全面和定量地描述功能缺陷，作为步态和肌肉力量沿着血管重建和许多骨再生指标的测量。这种复合损伤模型将作为一种新的模型，以测试新的组织工程结构和治疗的肌肉和骨骼研究骨再生的肌肉损伤的存在。进一步了解肌肉和骨骼在再生过程中的相互作用将有助于改善治疗方法。我在通过合作项目开发新型动物模型方面有着成功的记录，因此我有独特的资格在这个项目中取得成功。除了研究部分，这个奖学金将给我必要的技能，是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，赠款和手稿写作，教学和指导。Guldberg实验室被国际公认为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制研究人员。这将是一个很好的培训经验，我将为我的职业生涯做好准备。 公共卫生相关性：由创伤、退行性疾病或肿瘤切除引起的大面积骨缺损的处理仍然是骨科医生面临的最具挑战性的问题之一。关键是我们要开发实用有效的技术来修复大的多组织缺损。目前的治疗方法只有在存在足够的组织时才有效，即使如此，也可能导致疤痕形成和功能恢复有限。因此，拟议的研究将有利于公众通过确定有效的治疗策略，复合组织损伤持续通过广泛的创伤事件。