Effects of nitric oxide releasing poly(vinyl alcohol) hydrogel dressings on dermal wound healing in diabetic mice

Abstract

Healing of chronic wounds such as diabetic foot ulcers is a significant clinical problem. Methods of accelerating healing in these difficult lower extremity sites include use of growth factor-loaded gels, hyperbaric oxygen, grafts, and artificial skin replacements. Nitric oxide (NO) has been proposed as a possible active agent for enhancing wound healing. This study examines the in vitro and in vivo responses to a novel hydrogel that produces therapeutic levels of NO. A hydrogel wound dressing was fabricated using ultraviolet light-initiated polymerization from poly(vinyl alcohol) with a NO donor covalently coupled to the polymer backbone. NO release from the NO-modified hydrogel was shown to occur over a time period of up to 48 hours, and there was no associated decrease in fibroblast growth or viability in vitro associated with NO hydrogels. Fibroblasts in culture with NO hydrogels had an increased production of extracellular matrix compared with cells cultured without the NO hydrogels. Preliminary animal studies in a diabetic mouse, impaired wound healing model were conducted comparing low (0.5 mM) and high (5 mM) doses of NO. Time to complete closure was similar in control wounds and NO-treated wounds; however, at 8 days control wounds were significantly smaller than NO-treated wounds. By days 10 to 13 this delay was no longer apparent. Granulation tissue thickness within the wounds at days 8 and 15 and scar tissue thickness after wound closure were increased in animals exposed to higher dose NO hydrogels. The results of this study suggest that exogenous NO released from a hydrogel wound dressing has potential to modulate wound healing.

Effect of Zwitterionic Polymers on Wound Healing

“…Wound dressings that release NO [38][39][40] on the wound surface, wound dressings containing bFGF 41,42) and a glycosaminoglycan hydrogel film 43) have recently been developed for healing skin lesions. All of these dressings have been shown to enhance healing of a full-thickness excisional wound, but they have not yet been made available as commercial products.…”

Role of Nitric Oxide in Extracellular Matrix Metabolism and Inflammation in Diabetic Wound Healing

“…Prior studies have shown that introduction of a NO donor can improve wound healing (Shabani et al, 1996;Bohl-Masters et al, 2002). The mechanism(s) responsible for NOinduced healing remains unclear.…”

“…The wound healing rates in the diabetic treatment groups approximated the normal mice. In a study by Bohl-Masters et al, 2002, a polyvinyl alcohol hydrogel impregnated with NO donor was used to increase the local NO concentration in a wound healing model in diabetic and normal mice. They found that wound healing in the NO donor-treated diabetic mice was either the same or slightly less than in the control group.…”

Advances in bioprinted cell-laden hydrogels for skin tissue engineering

“…Hydrogels have been widely used to assist the regenerative and reparative processes of many tissues [41,198,199] and several studies were performed assessing their potential as wound healing adjuvant, mainly due to their porosity, permeability, viscoelastic properties and low immunogenicity (depending on the source) [21,39,64,114]. Hydrogels are defined as crosslinked 3D network structures obtained from a range of synthetic or natural polymers that can absorb and retain large amounts of water [7,168].…”