title: Fluorinated methacrylamide chitosan hydrogel systems as adaptable oxygen carriers for wound healing.
abstract: In this study a series of novel, biocompatible hydrogels able to repeatedly takeup and deliver oxygen at beneficial levels have been developed by conjugating various perfluorocarbon (PFC) chains to methacrylamide chitosan via Schiff base nucleophilic substitution, followed by photopolymerization to form hydrogels. The synthesized fluorinated methacrylamide chitosan (MACF) hydrogels were confirmed by high resolution (19)F NMR. Synthesized MACF hydrogels were tested for their ability to takeup and then release oxygen for future use in dermal wound healing. Depending on the PFC substitution type maximum O(2) uptake was observed within 2-6h, followed by complete release to the surrounding environment (5% CO(2)) within 12-120h at oxygen partial pressures of 1-25mm Hg h(-1), providing outstanding system tuning for wound healing and regenerative medicine. MACFs with the most fluorines per substitution showed the greatest uptake and release of oxygen. Interestingly, adding PFC chains with a fluorinated aromatic group considerably enhanced oxygen uptake and extended release compared with a linear PFC chain with the same number of fluorine molecules. MACF hydrogels proved to be readily reloaded with oxygen once release was complete, and regeneration could be performed as long as the hydrogel was intact. Fibroblasts were cultured on MACFs and assays confirmed that materials containing more fluorines per substitution supported the most cells with the greatest metabolic activity. This result was true, even without oxygenation, suggesting PFC-facilitated oxygen diffusion from the culture medium. Finally, MACF gradient hydrogels were created, demonstrating that these materials can control oxygen levels on a spatial scale of millimeters and greatly enhance cellular proliferative and metabolic responses.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Akron, 200 East Buchtel Common, Akron, OH 44325, USA.
authors.forename: Asanka
authors.initials: A
authors.lastname: Wijekoon
authors.forename: Natalie
authors.initials: N
authors.lastname: Fountas-Davis
authors.forename: Nic D
authors.initials: ND
authors.lastname: Leipzig
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D054879:Halogenation; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008855:Microscopy, Electron, Scanning; D041681:NIH 3T3 Cells; D010100:Oxygen / Q000737:chemistry*; D012212:Rheology / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000178:Acrylamides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan; C045985:methacrylamide; D010100:Oxygen