ISS: The Effects of Age on the Mechanochemical Feedback Loop for Extracellular Matrix Production by Fibroblasts in the Context of Wound Healing

这个项目的目标是了解衰老对愈合过程的影响。随着年龄的增长，人们对炎症和损伤的愈合效率降低。有证据表明，成纤维细胞（负责产生细胞外基质的细胞）内的变化在愈合反应的改变中起着重要作用。在这个项目中，来自塔夫茨大学的一个团队将评估细胞年龄和细胞外基质年龄对伤口愈合模型的影响。国际空间站（ISS）上的独特环境将被用来模拟与衰老相关的过程。该项目的成果将通过培养下一代科学家，鼓励初中和高中学生从事研究工作，并通过对伤口愈合随年龄增长的更基本理解来促进健康，从而为国家利益服务。该项目计划探索细胞外基质和成纤维细胞老化相关的变化及其相互作用，随着年龄增长和暴露在微重力下，影响组织功能障碍和愈合受损。虽然先前的工作已经评估了微重力对成纤维细胞和伤口愈合的影响，但尚未尝试在发育年龄的背景下评估这种影响，尽管愈合效果随年龄而显着变化。追求两个具体的研究目标。首先，研究人员将确定微重力对成纤维细胞表型的影响，作为组织类型和发育年龄的函数。 其次，将研究通过国际空间站上的微重力暴露模拟老化对组织基质的个体发育模拟物中伤口愈合反应的影响。一种新的丝细胞外基质水凝胶系统将部署解耦细胞和细胞外的贡献，这是第一次。这些研究将阐明与微重力相关的伤口愈合改变的机制，并为我们了解衰老如何影响地球上的这些相同现象提供信息。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。

The goal of this project is to understand the impact of ageing on the healing process. As people age, they heal less efficiently in response to inflammation and injury. There is evidence that changes within fibroblasts, the cells responsible for production of extracellular matrix, play a significant role in alterations to healing response. In this project, a team from Tufts University will assess the impact of cellular age and the age of the extracellular matrix on models of wound healing. The unique environment aboard the International Space Station (ISS) will be leveraged to simulate processes associated with ageing. The outcomes of this project will serve the national interest by training the next generation of scientists, encouraging students at the middle and high school levels to pursue careers in research, and by advancing health via a more fundamental understanding of wound healing with age.The project plans to explore how changes associated with ageing of the extracellular matrix and fibroblasts, and their interaction, influence tissue dysfunction and impaired healing with age and exposure to microgravity. While previous work has assessed the effects of microgravity on fibroblasts and wound healing, there has been no attempt to evaluate this impact in the context of developmental age, even though healing effectiveness varies significantly with age. Two specific research objectives are pursued. First, the investigators will determine the effects of microgravity on fibroblast phenotype as a function of tissue type and developmental age. Second, the impacts of simulated aging via microgravity exposure aboard the ISS on wound healing response in ontogenetic mimics of tissue stroma will be investigated. A novel silk-extracellular matrix hydrogel system will be deployed to decouple cellular and extracellular contributions to this process for the first time. These studies will elucidate the mechanisms of altered wound healing associated with microgravity and inform our understanding of how ageing impacts these same phenomena on Earth. This knowledge could lead to new treatments to promote better wound healing and restore tissue function throughout the body.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.