Nitric Oxide Delivery from Wound Dressings

Nitric oxide has been shown to promote angiogenesis through stimulation of VEGF and increase fibroblast collagen synthesis. The NO-producing hydrogels provide both a moist wound dressing and localized production of NO to improve healing.

:: Rationale

NO has multiple physiological roles at the cellular and tissue level. In wounded skin, NO has been reported as increasing granulation tissue formation and collagen synthesis. Delivery of NO from hydrogel wound dressings can benefit wound healing by providing NO at therapeutic levels and by creating a moist environment for optimal healing.

:: Technology Description

Fast crosslinking PVA based prepolymers (or the formed hydrogel), modified with amine groups, are exposed to NO gas. The amine groups act as nucleophiles and a complex forms between the prepolymers or hydrogel and NO. On exposure to physiological conditions, the NO is released by hydrolysis and is able to act at the site of delivery. PVA-NO hydrogels can be sterilized by filtration and shelf-life can be extended by storage at low temperature or low pH. The NO loading can be varied by altering the % amine substitution and the exposure time to NO gas.

:: Results to Date

Production of collagen by human dermal fibroblasts (HDF) increased in vitro (Figure A) while a relatively constant overall level of extracellular matrix (ECM) was maintained (Figure B).

A. Total Collagen Production	B. Total ECM Production

Preliminary studies have been conducted to examine the effect of PVA-NO hydrogels on wound healing in a genetically diabetic mouse model. Wound healing in this model is impaired, usually by a two to threefold decrease in wound closure rate and wound strength. This is similar to the impaired wound healing experienced by humans with diabetes and is thought to be due in part to reduction of NO production. Wound closure rate was not significantly different between control and PVA-NO hydrogels in the diabetic mouse model; however granulation tissue thickness and scar tissue thickness were substantially higher in the PVA-NO groups (see Figures C and D below) suggesting improved healing and wound strength.

C: Granulation Tissue Formation	D. Scar Tissue Formation

:: Patent Position

Issued patents for the fast crosslinking PVA hydrogel system. Patents pending for use of the PVA hydrogel system for preformed and in situ formed wound dressings and for nitric oxide producing hydrogel materials.

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