Using light therapy to accelerate wound healing

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Wound management has been an area of abundant research and clinical interest in veterinary medicine for decades. Whether treating naturally occurring wounds that present on emergency or surgical incisions created with care and precision, accelerating the healing process offers immense benefits to veterinarians, clients, and patients. Numerous medical interventions to improve cutaneous wound healing have been investigated, and in order to critically evaluate these treatments it is important to understand the biologic process behind wound healing.

Wound healing

Wound healing is a normal physiological process that aims to restore the skin’s natural barrier function through rebuilding injured tissue. It can be broken down into 4 highly integrated and overlapping phases that must occur in the proper sequence and within a specific time frame: hemostasis, inflammation, proliferation, and maturation.

Phase 1, hemostasis, begins within seconds when there is damage to tissue and blood vessels that causes blood to leak out of the surgical incision.¹ The blood vessels respond with vasoconstriction to restrict blood flow, followed by recruitment of platelets that aggregate and adhere to the damaged subendothelium to seal the defect.¹ Coagulation factors such as thromboplastin, which converts prothrombin to thrombin, are released from activated platelets and endothelial cells.¹ Thrombin then allows fibrinogen to be converted to fibrin, which leads to the formation of a fibrin clot that stabilizes the wound and acts as a scaffold to allow for movement of inflammatory cells. The clot also acts as a reservoir for platelet-released chemoattractants and growth factors that will be important in the later stages of wound healing.²

Phase 2, inflammation, begins when neutrophils and monocytes are recruited to the wound site by various chemoattractants.² Neutrophils begin arriving within minutes of injury and are tasked with cleansing the wound of contaminating bacteria as well as beginning fibroblast and keratinocyte activation.² Macrophages bridge the gap between inflammation and proliferation and play a major role in wound healing by cleansing and debriding the wound through removal of pathogenic organisms and matrical debris.² These macrophages, much like the platelets and neutrophils before them, also release numerous growth factors and cytokines that will recruit and activate fibroblasts and aid in angiogenesis.

Phase 3, proliferation, begins 3 to 5 days after injury and is the rebuilding phase in which new tissue made up of collagen and extracellular matrix is generated.¹ Cytokines released in this phase stimulate fibroblasts to proliferate and migrate into the wound along the fibrin clot. This occurs just before new networks of capillaries are formed.¹ Mature fibrous tissue orients parallel to the incision via tension lines, and this fibrin is then replaced as type III (immature) collagen is deposited.¹ Surgical wounds begin rapidly reepithelializing during this phase due to the close apposition of the skin edges.¹ In nonsurgical wounds, or wounds in which skin apposition is not attainable, granulation tissue begins forming at the wound edges and acts as the source for myofibroblasts, which are critical for wound contraction and reepithelialization.¹

Phase 4, maturation or remodeling, occurs when a sufficient amount of type III collagen has been deposited and is then remodeled into type I (mature) collagen that undergoes cross-linking. This cross-linked collagen becomes thicker and provides strength to the wound and a smaller, smoother scar. This final phase may take months to complete.

Numerous factors may impede healing at surgical sites, including secondary infections, excessive inflammation, reduced blood supply, exposure to antiseptics, and an overly dry wound bed.¹ To prevent such complications, many strategies have been employed, such as use of wound dressings and topical therapeutics, each requiring skilled management as well as client and patient compliance. Dressings may fall off due to poor adhesion, animals must be kept in E-collars to prevent self-trauma and removal, and topical medications may be difficult to administer. As such, accelerating and improving tissue repair at surgical sites would provide numerous benefits in the postoperative period.

A new approach to wound healing

Biofunctional materials, which promote tissue regeneration by interacting with light, represent an exciting development in wound healing management that has been studied widely in human patients and shows immense promise. This method, also known as photobiomodulation (PBM), is a nonthermal process that uses light-emitting diodes (LED) to excite chromophores in the mitochondria of various cell types. These mitochondria then begin making energy in the form of adenosine triphosphate, which has the downstream effect of modifying biological processes, including increasing fibroblast activation and collagen production.^3-7 PBM has been shown to work exogenously by stimulating photosensitizers to react with ambient oxygen and produce reactive oxygen species, which are toxic to microorganisms and eliminate undesirable tissue.⁸

Fluorescence biomodulation (FB) is a type of PBM that uses broader wavelengths with lower energy to penetrate the skin and stimulate healing.3 Phovia (Vetoquinol) is a novel FB product that uses a blue LED lamp (delivering light at peak wavelengths from 440 to 460 nm) and a photoconverter hydrogel containing specific chromophores that release low-energy photons in the form of fluorescent light. Phovia has been shown to have therapeutic efficacy and excellent safety in deep pyoderma, perianal fistulas, and interdigital pyoderma in dogs.^9-12

Phovia for surgical wound healing

A 2018 study assessed the use of Phovia in accelerating surgical site wound healing over a 13-day treatment course. Ten healthy, client-owned dogs undergoing routine orthopedic surgery were included in the study. Each dog served as its own control: 50% of the incision was treated with sterile saline cleansing followed by phototherapy with the Phovia system and 50% was treated solely with sterile saline cleansing. The control side was covered during treatment to prevent exposure to the LED lamp illumination. On the Phovia-treated side, photoconverter gel was applied in a layer 2 mm thick, the LED lamp was held approximately 5 cm above the skin, and the fluorescent light energy (FLE) was applied for 2 minutes beginning day 1 after surgery and repeated every 3 days until day 13. Outcomes were determined clinically using the ASEPSIS scale and were also assessed with histopathology and immunohistopathologic analysis on the last day of treatment.³

No adverse reactions to the treatments were reported, and clinical wound healing was satisfactory in both treated and untreated portions of the incision. It was in the histopathologic and immunohistochemical analyses where significant therapeutic potential was demonstrated. Areas treated with Phovia achieved a significantly lower histopathology score associated with complete re-epithelialization, decreased inflammation in the dermis, high neoangiogenesis, and more regular collagen deposition. In the treated samples, several key differences were noted. Increased expression of collagen type III and endogenous decorin provided evidence of improved dermal repair during the maturation/ remodeling phase. The expression of growth factors was notably different between the treatment and control samples, with an increase in epidermal growth factor (EGF) found in treated tissues only. EGF has been shown to reduce inflammation, accelerate re-epithelialization, and increase tensile strength in wound repair.^13-15 Expression of the proinflammatory cytokine TNF-a was lower in Phovia-treated samples, which also supported the histopathologic findings.16 Additionally, increased expression of Ki-67 in treated samples supported enhanced epithelial and mesenchymal cell proliferation, which is critical in improving wound healing. Based on these results, FLE showed immense promise for improving wound healing by stimulating the release of cytokines and promoting a more complete repair of the damaged tissue.³

Phovia for nonsurgical wound healing

Phovia also has been shown to potentially accelerate time to clinical resolution of deep pyoderma in dogs with twice-weekly application of the system.¹⁰ Although research has not yet been published regarding the use of Phovia to treat naturally occurring or contaminated wounds, the results of the surgical wound study combined with the results of this pyoderma study may suggest that nonsurgical or contaminated wounds also would benefit from FLE therapy.

Using Phovia in practice

The Phovia system is easy to use and can be tailored to meet the needs of clinics and their clients. Treatment time is minimal with a recommended illumination time of 2 minutes per site. Animals are reported to tolerate the treatment very well with no need for sedation or local analgesia in most pets. Veterinary technicians may be trained to perform the treatments, which offers an opportunity for increased technician satisfaction as well as allowing doctors to attend to other patients.

In the surgical wound study, Phovia was used every 3 days for a total of 5 treatments,³ whereas in the deep pyoderma, and interdigital pyoderma studies it was used twice weekly.^9,10,12 The repeated visits required for these treatments may seem somewhat daunting, however, they offer the added bonus of increased opportunities to assess wound healing and allow for early intervention and therapeutic changes if needed. At this time, initial investment for the Phovia system is $800 for the starter kit with 10 jars of gel and $150 for 5 jars of single-use photoconverter gel. Including the price of Phovia treatments in surgical estimates offers both financial and owner compliance assurances.

Conclusion

Phovia offers a unique opportunity to integrate a safe, effective, innovative, and proactive treatment into a practice’s surgical and emergency wound management. Potential benefits of this system include accelerated wound healing time at surgical sites and decreased usage of oral antimicrobials in contaminated wounds, all while using a system that is user friendly and well tolerated by pets.

References

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11. Marchegiani A, Tambella AM, Fruganti A, Spaterna A, Cerquetella M, Paterson S. Management of canine perianal fistula with fluorescence light energy: preliminary findings. Vet Dermatol. 2020;31(6):460-e122. doi:10.1111/vde.12890
12. Marchegiani A, Spaterna A, Cerquetella M, Tambella AM, Fruganti A, Paterson S. Fluorescence biomodulation in the management of canine interdigital pyoderma cases: a prospective, single-blinded, randomized and controlled clinical study. Vet Dermatol. 2019;30(5):371-e109. doi:10.1111/vde.12785
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