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

血管形成和细胞外基质(ECM)重塑是伤口愈合过程中的交叉过程。血管形成和细胞外基质重塑的协调程度决定了伤口是再生成功能组织还是形成疤痕。研究的目的是从基因和蛋白质表达的动态变化、血管形成的结构变化以及细胞外基质的力学性质等方面了解微重力对这些伤口愈合过程的影响。这将使用集成传感器的组织培养模型来实现，该模型模拟伤口愈合环境。该项目为陆基和天基研究提供了一个组织表征平台。这些实验工具还可能支持以ECM重塑和血管形成为目标的未来疗法的发展，以实现伤口愈合过程中的功能性组织再生。综合教育的目标是为高中和本科的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基于空间的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、交叉的过程。血管生成和ECM重建在空间和时间上协调的程度决定了伤口愈合是否会导致功能性组织再生或疤痕形成。本项目的研究目的是从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结构的变化以及ECM的力学特性等方面了解微重力对伤口愈合过程的影响。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、内皮网络形成和细胞外基质机械性能之间的多尺度相互关系。该项目还在一种新型的体外伤口愈合环境中生成了血管网络形成和早期伤口修复的动态概况，该环境结合了转化生长因子β刺激导致的成纤维细胞到肌成纤维细胞的表型转变。这项工作的一个重大进步将是实时测量由关键的肌成纤维细胞行为产生的细胞外基质硬化轮廓，包括胶原产生和收缩。此外，使用3D共培养系统，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。综上所述，该项目利用自主的组织属性感知，促进了有关微重力对伤口愈合过程中组织重塑过程的影响的知识。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.