Collaborative Research: ISS: Real-time Sensing of Extracellular Matrix Remodeling during Fibroblast Phenotype Switching and Vascular Network Formation in Wound Healing

合作研究：ISS：实时感知成纤维细胞表型转换和伤口愈合中血管网络形成过程中的细胞外基质重塑

• 批准号: 2126170
• 负责人: Shayn Peirce-Cottler
• 金额: $ 17.5万
• 依托单位: University of Virginia Main Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2126170&HistoricalAwards=false
• 关键词: Collaborative; Research; ISS; Real; time

Blood vessel formation and extracellular matrix (ECM) remodeling are intersecting processes in wound healing. The extent to which blood vessel formation and ECM remodeling are coordinated determines if wounds regenerate to functional tissue or form scars. The research objective is to understand the effects of microgravity on these wound healing processes in terms of the dynamic changes in gene and protein expression, structural changes in blood vessel formation, and ECM mechanical properties. This will be accomplished using a sensor-integrated tissue culture model that mimics a wound healing environment. This project advances a tissue characterization platform for both terrestrial- and space-based research. These experimental tools may also support the development of future therapeutics that target ECM remodeling and blood vessel formation for functional tissue regeneration during wound healing. The integrated educational objective is to create an interactive virtual educational platform for high-school and undergraduate biology students to improve interest and competency in engineering concepts and space-based biology research.Angiogenesis and extracellular matrix (ECM) remodeling are critical, intersecting processes in wound healing. The extent to which angiogenesis and ECM remodeling are spatially and temporally coordinated determines if wound healing leads to functional tissue regeneration or scar formation. The research objective of this project is to understand the effects of microgravity on wound healing processes in terms of the dynamic changes in fibroblast and endothelial cell (EC) gene and protein expression, structural changes in capillary networks during angiogenesis, and ECM mechanical properties. This will be accomplished using a sensor-integrated 3D co-culture model that mimics a wound healing environment via exogenous transforming growth factor beta stimulation. Hence, this project will leverage a new experimental platform to explore multi-scale interrelationships among gene and protein expression, endothelial network formation, and ECM mechanical properties in real-time. This project also generates dynamic profiles of vascular network formation and early wound repair in a novel in vitro wound healing environment that incorporates fibroblast-to-myofibroblast phenotypic transitions resulting from transforming growth factor beta stimulation. A significant advance contributed by this work will be the measurement of real-time ECM stiffening profiles resulting from key myofibroblast behaviors, including collagen production and contraction. Furthermore, this work provides new data regarding the impact of microgravity on fibroblast phenotypic switching, ECM stiffening, and vascular network formation using a 3D co-culture system. In summary, this project advances knowledge regarding the effects of microgravity on tissue remodeling processes during wound healing using autonomous tissue property sensing.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.

血管形成和细胞外基质（ECM）重塑是伤口愈合中的交叉过程。血管形成和ECM重塑协调的程度决定了伤口是否再生为功能组织或形成疤痕。研究目的是了解微重力对这些伤口愈合过程的影响，包括基因和蛋白质表达的动态变化、血管形成的结构变化和ECM机械特性。这将使用模拟伤口愈合环境的传感器集成组织培养模型来实现。该项目为地面和空间研究提供了一个组织表征平台。 这些实验工具还可以支持未来治疗方法的发展，这些治疗方法靶向ECM重塑和血管形成，用于伤口愈合期间的功能性组织再生。综合教育目标是为高中和本科生物学学生创建一个互动的虚拟教育平台，以提高他们对工程概念和天基生物学研究的兴趣和能力。血管生成和细胞外基质（ECM）重塑是伤口愈合中关键的交叉过程。血管生成和ECM重塑在空间和时间上协调的程度决定了伤口愈合是否导致功能性组织再生或瘢痕形成。该项目的研究目标是了解微重力对伤口愈合过程中成纤维细胞和内皮细胞（EC）基因和蛋白表达的动态变化，血管生成过程中毛细血管网络的结构变化以及ECM机械性能的影响。 这将使用传感器集成的3D共培养模型来实现，该模型通过外源性转化生长因子β刺激来模拟伤口愈合环境。 因此，该项目将利用一个新的实验平台来实时探索基因和蛋白质表达，内皮网络形成和ECM机械特性之间的多尺度相互关系。该项目还在一种新的体外伤口愈合环境中生成血管网络形成和早期伤口修复的动态概况，该环境包含转化生长因子β刺激引起的成纤维细胞至肌成纤维细胞表型转变。这项工作的一个重大进展将是测量由关键肌成纤维细胞行为（包括胶原蛋白的产生和收缩）引起的实时ECM硬化曲线。此外，这项工作提供了关于微重力对成纤维细胞表型转换，ECM硬化和血管网络形成的影响的新数据，使用三维共培养系统。 总之，该项目利用自主组织特性传感技术，在伤口愈合过程中推进了关于微重力对组织重塑过程影响的知识。该奖项反映了NSF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。