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

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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.