CAREER: Purposeful Tissue-Engineered Skeletal Muscle: Advancing Research and Education

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。患有2型糖尿病等疾病的患者的骨骼肌的特征是脂肪细胞（即脂肪细胞）的丰度增加。白色、棕色和米色脂肪细胞可以存在于组织中，每种类型的脂肪细胞以不同的方式影响组织功能。该研究与教师早期职业发展计划（Career）项目一起完成，将促进对糖尿病骨骼肌中不同类型脂肪细胞以及肌肉修复和再生过程的理解。骨骼肌组织工程模型将用于探索脂肪细胞在骨骼肌中的作用，使用模拟糖尿病和肌肉损伤的条件。研究目标将与教育和推广相结合，以广泛影响STEM学生，并制定更有针对性的指令，以影响退伍军人和代表性不足的少数民族。本CAREER项目的总体目标是全面了解2型糖尿病进展过程中骨骼肌中脂肪细胞依赖的作用以及损伤后的修复和再生过程。第一个目的是确定2型糖尿病、脂肪细胞类型和脂肪细胞分化能力对骨骼肌特性的影响。组织工程骨骼肌模型将用于检查脂肪细胞类型和糖尿病如何影响代谢；改变肌肉内脂肪细胞表型（诱导白色到棕色或米色转变）的能力，以及sirtuin-1 （SIRT1）在介导这些变化中的作用。第二个目的是阐明骨骼肌脂肪细胞在骨骼肌再生中的作用。脂肪细胞类型在骨骼肌功能结果恢复中的作用将被质疑。使用损伤将确定脂肪细胞依赖效应可能被改变的条件。使用一个工程模型，其中实现了损伤和2型糖尿病，为更好地理解这些方面提供了机会，因为它们与糖尿病骨骼肌中的脂肪细胞有关。这些知识将导致新的研究途径，支持平台的发展，以开发针对骨骼肌并发症的个性化方法。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). The skeletal muscles of patients with diseases like Type 2 diabetes are characterized by an increase in the abundance of fat cells, known as adipocytes. White, brown, and beige adipocytes can exist within tissues, with each type influencing tissue function in distinct ways. The research completed with this Faculty Early Career Development Program (CAREER) project will advance the understanding of the different types of adipocytes in diabetic skeletal muscle, and during muscle repair and regeneration. A tissue-engineered model of skeletal muscle will be used to explore the role of adipocytes in skeletal muscle using conditions that mimic diabetes and muscle injury. Research objectives will be integrated with education and outreach to broadly impact STEM students, with more targeted directives to influence Veterans and underrepresented minorities.The overall goal of this CAREER project is to develop a comprehensive understanding of adipocyte-dependent effects in skeletal muscle during the progression of Type 2 diabetes and during repair and regeneration after injury. The goal of the first objective is to determine the effects of Type 2 diabetes, adipocyte type, and adipocyte differentiation capacity on skeletal muscle properties. The tissue-engineered skeletal muscle model will be used to examine how adipocyte type and diabetes influence metabolism; the ability to change adipocyte phenotype (inducing a white to brown or beige transition) within muscle, and the role of sirtuin-1 (SIRT1) in mediating these changes. The goal of the second objective is to elucidate the role of skeletal muscle adipocytes in skeletal muscle regeneration. The role of adipocyte type in recovery of functional outcomes in skeletal muscle will be interrogated. The use of injury will identify conditions in which adipocyte-dependent effects may be altered. The use of an engineered model where both injury and Type 2 diabetes are implemented provides an opportunity to better understand these facets as they relate to adipocytes in diabetic skeletal muscle. This knowledge will lead to new avenues for investigation, supporting the development of platforms to develop personalized approaches for targeting skeletal muscle complications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.