Worldwide, approximately 30.3 million people (9.4% population) in US had diabetes in 2015. Every year, 1.3 million new diabetes cases are identified. 3-4 million of diabetic patients develop wounds, and 1 in 5 patients in severe cases of diabetic wounds require amputation. Chronic wounds, including diabetic wounds, show oxygen tensions as low as 5 mm Hg partial pressure of oxygen, (Po2), compared to healthy tissue which is maintained at 40 mm Hg. Further complicating this, reactive oxygen species (ROS) are elevated during inflammation leading to oxidative stress. Oxygen therapy has shown benefits in healing chronic wounds while managing inflammation. Current oxygenating treatments are expensive and difficult to use. The primary objective of my project was to evaluate fluorinated methacrylamide chitosan (MACF) hydrogels to deliver beneficial levels of oxygen to acute and diabetic wounds to enhance wound healing responses. All the studies in this thesis focus on testing MACF hydrogel dressings in vitro and in vivo to establish safety and efficacy of the treatment in acute and diabetic wound models. Finally, microspheres were formulated and studied from PFC modified chitosan for oxygenation in 3D cultured spheroids and organoids, presenting a future potential extension of the MACF technology. The overall hypothesis of these studies was that MACF hydrogel dressings can provide biological levels of oxygen in wound healing thereby improving wound healing responses in both acute and chronic wound models.

I also hypothesized that fluorinated chitosan based microparticles could help reduce tissue hypoxia in tissue spheroids limiting the size of the necrotic core. From these studies, first in Aim 1, I validated the antioxidant capacity of MACF while simultaneously delivering oxygen. Next, in Aim 2, I evaluated MACF hydrogel dressing in the acute rat, establishing metabolomics workflow to study treatment response, and in porcine full thickness model expanding this work to the transgenic diabetic mouse model. Finally, I developed chitosan-PFC microspheres for modulating local oxygen microenvironments in spheroids and organoids and demonstrated a reduction in hypoxia upon increasing % loading of microspheres in spheroids.