Fibrotic diseases are responsible for ~45% of deaths in developed countries. Fibrosis is caused by aberrant scaring of tissue or organs. In healthy tissues, cells within tissues or organ will begin the wound healing response after some type of injury. This response includes depositing new tissue to heal the injured site. In fibrosis, this wound healing response is dysfunctional where cells continuously deposit new tissue causing gradual stiffening of the tissue or organ, i.e. scaring. The cells responsible for this scar formation are activated fibroblasts or myofibroblasts.
Fibrotic diseases are characterized by a persistent myofibroblast cell population. Myofibroblasts continuously produce new scar tissue further exacerbating disease. The molecular mechanisms that led to myofibroblast persistence are unknown. I use photodegradable PEG hydrogels where I can mimic healthy (soft hydrogels) or fibrotic (stiff hydrogels) diseased tissues. By culturing animal derived fibroblasts on these hydrogels, I can measure their response to healthy or diseased tissue stiffness. We see that diseased (stiff) environments cause fibroblasts to activate to myofibroblasts while healthy (soft) environments maintain the quiescent fibroblast phenotype, as measured by alpha smooth muscle actin (aSMA). Using this hydrogel system, I can probe how cells respond to extended exposure to diseased environments using techniques including next-generation sequencing, high-throughput imaging, and drug screening.