Oxygen plays a significant role in wound healing and growing evidence shows that tissue oxygenation levels are an important rate limiting factor in the dermal healing response. Specifically, non-healing diabetic chronic wounds (defined as lasting >6 wks.) often show devastatingly low oxygen concentrations, as low as 5 mmHg oxygen partial pressure (PO2 ). Diabetes affects more than 25 million Americans and is forecasted to increase by 1-2 million cases each year for the next five years. It is estimated that up to 25% of all diabetics will develop a foot ulcer, and a fifth of these cases will result in a chronic non-healing wound that requires amputation. Oxygen treatment has been demonstrated to promote chronic wound healing by enhancing metabolism, ECM synthesis and neovascularization, while limiting antimicrobial activity. Despite the benefits of supplemental oxygen, current oxygen delivery therapies are intermittent, inconvenient for the patient, and require access to expensive and specialized equipment. There is significant need for a simple wound care dressing able to support regenerative levels of oxygen and to supplement or possibly supplant current therapies (hyperbaric oxygen, topical oxygen via tent/bag). This proposal provides a UV polymerized hydrogel-based methodology in the form of a dressing that has the potential to provide uniform and tunable oxygenation across the wound. We have recently invented a biocompatible photocrosslinkable chitosan with special chemical additions. Our approach is innovative because it allows the creation of injectable/moldable hydrogel wound dressings that can sustain healing levels of oxygen to a wound for greater than 12 h, and potentially up to 5 d. Our primary hypothesis is that our oxygen loaded hydrogel platform will provide both enhanced short-term and long-term skin healing responses significantly faster and more completely than unoxygenated scaffolds or a commercial dressing (Puracol Plus(r)). To test these hypotheses, this R15 AREA proposal has four specific aims: 1. To create chitosan based oxygen delivery hydrogels and characterize their properties;2. To refine the hydrogels in vitro;3. To conduct preclinical in vivo proof of concept studies to evaluate safety and efficacy o the hydrogels in wound healing;4. To engage graduate, undergraduate and high school students in various areas of biomedical research. The ability to supply oxygen from a convenient hydrogel dressing could transform chronic wound healing while providing new tools for studying the role of oxygen in correcting other tissue injuries, disease or disorders.
The primary goal of this R15 AREA proposal is to create a tailorable, easy to use, bandage-sized hydrogel treatment able to supply healing levels of oxygen directly to a wound. This work would significantly improve and accelerate wound healing, especially in chronic cases where oxygen levels are devastatingly low. Furthermore, this work is relevant to public health due to its potential to create new therapies for chronic wounds with broad reach.
|Lawrence, Patrick G; Patil, Pritam S; Leipzig, Nic D et al. (2016) Ionically Cross-Linked Polymer Networks for the Multiple-Month Release of Small Molecules. ACS Appl Mater Interfaces 8:4323-35|
|Patil, Pritam S; Fountas-Davis, Natalie; Huang, He et al. (2016) Fluorinated methacrylamide chitosan hydrogels enhance collagen synthesis in wound healing through increased oxygen availability. Acta Biomater 36:164-74|