Fluorinated methacrylamide chitosan hydrogels enhance collagen synthesis in wound healing through increased oxygen availability

Abstract

In this study, methacrylamide chitosan modified with perfluorocarbon chains (MACF) is used as the base material to construct hydrogel dressings for treating dermal wounds. MACF hydrogels saturated with oxygen (+O2) are examined for their ability to deliver and sustain oxygen, degrade in a biological environment, and promote wound healing in an animal model. The emerging technique of metabolomics is used to understand how MACF+O2 hydrogel dressings improve wound healing. Results indicate that MACF treatment facilitates oxygen transport rate that is two orders of magnitude greater than base MAC hydrogels. MACF hydrogel dressings are next tested in an in vivo splinted rat excisional wound healing model. Histological analysis reveals that MACF+O2 dressings improve re-epithelialization (p<0.0001) and synthesis of collagen over controls (p<0.01). Analysis of endogenous metabolites in the wounds using global metabolomics demonstrates that MACF+O2 dressings promotes a regenerative metabolic process directed toward hydroxyproline and collagen synthesis, with confirmation of metabolite levels within this pathway. The results of this study confirm that increased oxygen delivery through the application of MACF+O2 hydrogels enhances wound healing and metabolomics analyses provides a powerful tool to assess wound healing physiology.

Statement of significance: This work presents the first application of a novel class of oxygen delivering biomaterials (methacrylamide chitosan modified with perfluorocarbon chains (MACF)) as a hydrogel wound dressing. This manuscript also contains strong focus on the biochemical benefits of MACF dressings on underlying mechanisms vital to successful wound healing. In this vein, this manuscript presents the application of applied metabolomics (tandem mass spectroscopy) to uncover biomaterial interactions with wound healing mechanisms. We believe the approaches described in this manuscript will be of great interest to biomedical scientists and particularly to researchers studying wound healing, metabolomics, applied biomaterials and regenerative medicine.

Keywords: Chitosan; Metabolomics; Oxygen delivery; Perfluorocarbons; Wound healing.