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，我可以从中为作为独立研究者的职业建立基础。该提案的目的是开发一个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构建体的植入以及所得的组织再生和肢体功能。假设在周围肌肉受伤的情况下，骨再生将受到损害，并且使用新型的组织工程肌肉结构来克服这种障碍，以促进肌肉和骨骼再生。解决这一假设的具体目的是：在大鼠中开发复合损伤模型，并定量研究肌肉损伤对骨骼再生和肢体功能恢复的影响。特定的目标II-用于定量分析复合损伤模型中新型肌肉疗法和构建体对骨再生的功能贡献。我们将全面和定量地将功能不足作为步态和肌肉强度以及血运重建和众多骨再生指标的量度。该复合损伤模型将作为一种新模型，用于测试新型组织工程结构和肌肉和骨骼的治疗剂，以研究在肌肉损伤存在下骨骼再生的新模型。在再生过程中，进一步了解肌肉与骨骼之间的相互作用将有助于改善治疗方法。我在通过协作项目开发新型动物模型方面有着成功的记录，因此具有在该项目中取得成功的独特资格。除研究组成部分外，该奖学金还将为我提供成功的独立调查员的必要技能。我将接受针对新动物模型，赠款和手稿写作，教学和指导的手术技术培训。古尔德伯格实验室在国际上被认为是在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轨道研究者。对我来说，这将是一次极好的培训经验，这将为我的职业生涯做好准备。 公共卫生相关性：由创伤，退化性疾病或肿瘤切除引起的大骨缺损的管理仍然是骨科医生面临的最具挑战性的问题之一。至关重要的是，我们要开发可实用且有效地修复大型多组织缺陷的技术。当前的疗法只有在存在足够的组织时才有效，即使到那时，也可能导致疤痕形成和功能恢复有限。因此，拟议的研究将通过确定通过广泛的创伤性发生率遭受的复合组织损伤的有效治疗策略来使公众受益。