ABSTRACT
Research has shown that nitric oxide (NO) enhances wound healing. The incorporation of NO into polymers for medical materials and surgical devices has potential benefits for many wound healing applications. In this work, acrylonitrile (AN)-based terpolymers were electrospun to form non-woven sheets of bandage or wound dressing type materials. NO is bound to the polymer backbone via the formation of a diazeniumdiolate group. In a 14 day NO release study, the dressings released 79 µmol NO g(-1) polymer. The NO-loaded dressings were tested for NO release in vivo, which demonstrate upregulation of NO-inducible genes with dressing application compared to empty dressings. Studies were also conducted to evaluate healing progression in wounds with dressing application performed weekly and daily. In two separate studies, excisional wounds were created on the dorsa of 10 mice. Dressings with NO loaded on the fibers or empty controls were applied to the wounds and measurements of the wound area were taken at each dressing change. The data show significantly enhanced healing progression in the wounds with weekly NO application, which is more dramatic with daily application. Further, the application of daily NO bandages results in improved wound vascularity. These data demonstrate the potential for this novel NO-releasing dressing as a valid wound healing therapy.
Subject(s)
Bandages , Lactic Acid , Neurotransmitter Agents , Nitric Oxide , Polymers , Wound Healing/drug effects , Animals , Cell Proliferation/drug effects , Collagen/biosynthesis , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Lactic Acid/chemistry , Lactic Acid/pharmacology , Male , Mice , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Neurotransmitter Agents/chemistry , Neurotransmitter Agents/pharmacology , Nitric Oxide/chemistry , Nitric Oxide/pharmacology , Polyesters , Polymers/chemistry , Polymers/pharmacology , Rats , Rats, Sprague-Dawley , Tissue EngineeringABSTRACT
The purpose of this study was to evaluate efficacy and safety of a gadolinium (Gd) zeolite suspension as an oral MRI contrast agent. Serial dilutions of GADO-LITE Oral Suspension 1,2-300 micrograms of Gd(III)/mL) were prepared. MRI (T1 and T2 weighted) of standards and dogs (precontrast and postcontrast) were performed. Toxicity and Gd absorption were also assessed. Subsequently, 30 normal male adult volunteers were divided into six groups of five subjects each. Gd zeolite po suspension was administered before and after MRI in volumes and concentrations ranging from 250 to 1500 mL; 6 to 60 micrograms of Gd+3/mL. The images were rated (efficacy score) by a blinded reader. Vital signs, blood chemistries and urinalysis were recorded. Gadolite Oral Suspension produced excellent enhancement of the dog gastrointestinal (GI) tract. No toxicity or absorption of Gd was observed in dogs receiving doses up to 4 times the anticipated human dose daily for 14 consecutive days. In clinical trials, Gd zeolite significantly improved the efficacy scores for all groups and all pulsing sequences (all P values < .05). Efficacy scores and signal intensities generally increased with concentration and volume. No Gd was detected in blood or urine specimens. No significant adverse events were reported. Gd zeolite is a promising contrast medium for enhancement of the GI tract in MRI.
