Nitric Oxide for Wound Care

February 28, 2023

Sponsored article provided by Noxsano.

In veterinary medicine wounds are common! They range from the simple scrape to the “serious life- and limb-threatening.” Whatever the severity of the wound, careful management by the veterinarian and their staff is needed for healing and infection control. This can take significant resources at a veterinary practice and compliance from the pet parent. Wound care products today mostly protect the wound site while letting nature take its course. Nature often does not cooperate and wounds are then slow to heal, stall, or worse. Broad spectrum antibiotic use is common to control infection. Multiple daily dressing changes strain already busy practices. A new approach that mitigates these issues is sorely needed for veterinary wound care.

Nitric Oxide: Part of the Body’s Innate Response to Healing

Successful wound healing depends on a complex interplay of many physiological processes, all working correctly together to repair damaged tissue and restore the functional barrier properties of the skin. Within veterinary medicine, positive outcomes are challenged by a host of factors, such as wound location, wound type, and infection. Fortunately, advancements in medicine continue to shed light on the complex physiological processes that drive wound healing, enabling novel therapies to improve healing with even the most challenging of wounds. Therapeutic nitric oxide is one such advancement. A small, diatomic gas, nitric oxide is produced in vivo by the enzyme nitric oxide synthase which converts L-arginine to L-citrulline releasing nitric oxide. Wound healing is primarily controlled by endothelial nitric oxide synthase. Endothelial nitric oxide synthase is activated when a wound occurs and then orchestrates the cascade of processes necessary for wound closure.

A Key Regulator of the Wound Healing Response

Nitric oxide coordinates proliferation, differentiation, and apoptosis in wound healing. Nitric oxide has been shown to upregulate expression of endogenous collagenase, stimulate the proliferation of endothelial cells, protect endothelial cells from apoptosis, and mediate vascular endothelial growth factor (VEGF) production. These effects of nitric oxide on endothelial cells stimulate autolytic debridement, proliferation and angiogenesis, the formation of new capillaries. Together these processes remove damaged tissue and provide new, well perfused tissue to replace it. Nitric oxide also coordinates increased collagen synthesis and deposition in the final phases of wound healing ensuring strong new tissue in the healed wound.

A Natural Antimicrobial

Nitric oxide has two distinct antimicrobial functions. It is generated during the initial oxidative burst and in combination with other species provides a potent chemical antimicrobial. These induce broad spectrum damage to pathogens caused by nitrosative and oxidative reactions. The damage sustained by the pathogens subject to these chemical processes is extensive. Few planktonic bacteria are able to escape the antimicrobial effect of nitric oxide and associated reactive species. Nitric oxide further controls immune cell signaling and the biochemical reactions which are used to defend against bacteria, fungi, viruses, and parasites. Finally, nitric oxide is also a biological signal that controls the dispersal of biofilms to the more susceptible planktonic bacteria. Biofilms are notoriously persistent and generally very resistant to antimicrobials and antibiotics. Planktonic bacteria are much more sensitive to antimicrobials and antibiotics.

Restore by Noxsano: A New Tool in Wound Healing

The presence and amount of nitric oxide are critical to wound healing. The challenge for the therapeutic application of nitric oxide has been delivering the correct amount of nitric oxide safely, efficiently, and effectively. Much effort has been expended on methods to deliver nitric oxide and the recent introduction of Restore by Noxsano is the first veterinary wound product to incorporate a simple effective nitric oxide delivery system. Restore veterinary wound pads and wound gels enable controlled topical delivery of nitric oxide, directly to the wound bed, preventing infection and actively stimulating the physiological processes needed to drive wound closure. This novel treatment provides reliable wound healing and infection control across the whole spectrum of wound healing:

  • Nitric oxide treatment was found to dramatically speed the healing of dangerous wounds healing by second intention such as degloving and the removal of large tumors. It’s ability to drive the growth of new tissue allows the wound to progress rapidly while controlling infection reducing the need for antibiotics.
  • Nitric oxide has worked well for the treatment of burn wounds. Burns cauterize the tissue which results in severely decreased vascular supply to the wound bed as well as an increased inflammatory response. Nitric oxide’s ability to drive angiogenesis, enables the re-vascularization of the wound bed speeding healing and allowing for a full recovery.
  • Sutured surgical incisions present an infection and dehiscence risk. Nitric oxide treatment provides infection control, even in a deep incisions, and faster formation of the new tissue needed to connect the two sides of the closed incision.
  • Minor wounds can also benefit from the application of nitric oxide. Improved blood flow and rapid epithelialization resulting from the nitric oxide speeds recovery and can eliminate the need for antibiotics to control potential infection.

Speeding or restarting wound healing after injury, surgery, or disease, and returning the animal to full health as quickly as possible is a primary goal in veterinary care. Rapid healing means lower stress on the animal, reduced risk of infection, and lower stress and cost to the animal’s owner. Topical delivery of nitric oxide represents a novel addition to the veterinary medicine toolbox, enabling treatment of a wide range of wounds and increasing chances of positive patient outcomes.

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