CAREER: Dynamic Microgels that Mimic Platelet Behavior to Promote Healing

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Nontechnical AbstractPlatelets are blood cells that play an important role in stopping bleeding after injury. After bleeding stops, platelets also help the injured tissue heal. Before injury, platelets circulate in the blood stream and have a compact and round shape. This shape ensures that platelets are able to effectively interact with the blood vessel wall if injury occurs. Once injury occurs, signals at the injury site cause the platelet to change shape, going from small and round to spread and star-shaped. This shape change in response to injury is critical for platelets to both stop bleeding and then help to repair the damage tissue after a clot forms. The research component of this project focuses on the development of a new material that mimics the ability of platelets to change shape in response to injury. The developed materials will be tested for their ability to change shape in response to injury signals and for their ability to stop bleeding and improve healing. This proposal will also focus on community outreach in the state of North Carolina. The goals of the outreach component of this project are to increase awareness and support for biomimetic materials engineering. Biomimetic materials are materials that mimic certain aspects of natural systems, such as the materials described in this proposal that mimic platelet function. The outreach goals will be achieved by designing new materials for K-12 summer camps and day camps and by giving talks at local museum events. Technical AbstractNatural platelets are pivotal to hemostasis and tissue repair, and platelet shape change in response to thrombin at the wound site is critical for these functions. Prior to injury, platelets display a small, round morphology that enhances margination to the vessel wall; effective margination is essential for rapid clot formation. At the injury site, thrombin activates platelets and induces a significant platelet shape change. This shape change is required for platelet-mediated clot retraction, which contributes to long-term healing. However, the relationship between wound-triggered shape change of platelet-mimetic materials and hemostatic and wound healing outcomes has not been defined. To that end, the over-arching goal of this research project is to develop a wound-triggered, platelet-mimetic microgel that, like native platelets, activates and changes shape in response to thrombin. The research objectives are: 1) Design platelet-mimetic particles that activate and change shape in response to thrombin at the wound site and define the relationship between thrombin concentrations and shape change dynamics; 2) Determine the effect of shape change on particle margination and clotting kinetics; 3) Determine the effect of shape change on clot retraction and wound healing dynamics. The outreach component of this proposal will utilize a two-pronged approach to increase awareness and support for biomimetic materials engineering in the state of NC through 1) the development of educational experiences for K-12 students and 2) participation in museum-based community outreach events. The educational component will integrate with the research component by providing students with hands-on experience with biomimetic materials engineering.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.