Endothelial Response in 2D and 3D to Doses of Photosensitive Carbon Monoxide Releasing Molecules with Improved Activation
Huynh, Nicholas Duc
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Cardiovascular disease (CVD) is the leading cause of death worldwide in large part due to atherosclerotic obstruction of blood vessels. Limitations with current treatment approaches include restenosis in stenting and viable donor-tissue for bypass grafts, and this has motivated research combining the fields of drug delivery and tissue engineering for alternative approaches. The use of carbon monoxide as a potential therapeutic agent in the treatment of CVD has shown potential impacts on vasodilation and anti-inflammation. The goal of this study was to develop a system to elucidate the response of endothelial cells post-exposure to different concentrations of carbon monoxide releasing molecules (CORMs) in 2D and 3D culture. This was achieved by conducting two main studies utilizing DK3 and DK4 photoCORMs. The initial study investigated release kinetics of DK3 and DK4 after 470 nm light activation, demonstrating CO release in cell culture. Further, in vivo biocompatibility was validated via vascular graft implantation of PCL/DK3 into a rat model. Surface modification studies utilized bioactive proteins for improving cell adhesion. Impacts of DK4 concentration on endothelial cell response was tested using spincoated films and electrospun meshes of 90% PCL and 10% collagen. Experiments also investigated effects with and without exposure to a 470 nm blue-light. Results indicated that incorporation and activation of DK4 maintains cellular function over time as seen in ve-cadherin fluorescence imaging, whereas control conditions without DK4 observed decreased cell functionality potentially from blue-light effects. These studies will further help to improve understanding the impact of CO on cellular response in 2D and 3D environments.