Healing rays

The integrity of healthy skin has a crucial role in maintaining physiological homeostasis of the human body. The largest organ system of the body, it plays pivotal roles in the protection against mechanical forces and infections, fluid imbalance, synthesis of vitamin D and thermal regulation. As a protective shield from the external environment, the skin is constantly exposed to potential injury and thus wound healing is a vital process for the survival of all higher organisms.1 The skin as an intricate structure is composed of the epidermis and dermis, including the dermal adipocyte layer.

Skin wound healing is a dynamic and highly regulated process of cellular, humoral and molecular mechanisms that begins directly after wounding and may last for years. Every tissue disruption of normal anatomic structure with consecutive loss of function can be described as a wound. They can be defined as open or outer wounds, whereas closed or inner wounds describe injury or ruptures of inner organs and tissue with intact skin.2 Physiological regulation of skin wound healing is a complex process dependent on many cell types and mediators interacting in a highly sophisticated sequence. These are four highly integrated and overlapping phases; hemostasis, inflammation, proliferation and tissue remodelling or resolution. They occur in a proper sequence at a specific time and continue for a specific duration. Any imbalance in these processes can cause impaired tissue repair and scarring.

HEMOSTASIS

The first phase of hemostasis occurs immediately with vascular constriction and fibrin clot formation. Pro-inflammatory cytokines and growth factors are released, and once bleeding is controlled the inflammatory markers migrate into the wound, creating an inflammatory or “lag” phase. Neutrophils, macrophages and lymphocytes infiltrate the area, each with specific roles in the inflammatory phase. Neutrophils are crucial in the phagocytosis and clearance of bacteria and degradation of necrotic tissue.

Macrophages play multiple roles in wound healing initially in releasing cytokines that promote the inflammatory response (usually after three days). Together with the neutrophils they clear apoptotic cells from the area of tissue damage. They then undergo phenotype transition that stimulates keratinocytes, fibroblasts and angiogenesis to promote tissue repair or proliferatio2-5

PROLIFERATION

The proliferation phase is the healing process (usually commencing within three to 10 days, dependant on the degree and depth of tissue damage), where the wound surface is covered, and formation of granulation and restoration of the vascular network occurs. Fibroblasts migrate along the fibrin network and the beginning of re-epithelialisation from the wound edges occurs due to capillary sprouting and subsequent angiogenesis. This process is supported by the adjacent keratinocytes and epithelial stem cells for the adjacent hair follicles or sweat glands, releasing a myriad of different cytokines and growth factors.

These processes support collagen formation, capillary growth and granulation tissue at the site of injury. The fibroblasts produce collagen as well as glycosaminoglycans and proteoglycans which are the major components of the extra cellular matrix (ECM). The wound healing enters its final stage of remodelling which can last for years.1, 4-6

WOUND MANAGEMENT

In everyday clinical practice wound care occupies a significant place. Chronic wounds pose a serious public health problem, severely affecting the quality of life and influencing decreased mobility and loss of productivity, creating a burden of expenditure in healthcare. These challenges require innovative, costeffective approaches to accelerate healing and reduce the incidence of bacterial infection, sequentially reducing the impact on healthcare.7

Light therapy is recognised as one of the oldest therapeutic modalities used to treat various health conditions. The ancient Egyptians harnessed the benefits of sunlight and latterly the observations of physicians in the 19th and 20th century identified the clinical benefits of using phototherapy and laser for healing without the risk of skin cancers associated with sun exposure. However, the seminal work by NASA using low light emitting diodes (LLED) with specific wavelengths accelerated the natural wound healing process, reducing the concerns with lasers such as expense, safety concerns and trained personnel to operate them. Their results demonstrated that red and near infrared (NIR) delivered at the correct parameters gave therapeutic benefit. This “photobiostimulation” heralded the efficacy of light on wound healing.8

“Light therapy is recognised as one of the oldest therapeutic modalities used to treat various health conditions”

LEDs utilise high-efficiency semiconductors to produce non-coherent, non-collimated light in the visible and invisible ranges of the electro-magnetic spectrum with simultaneous emission of photon energy. This energy must be absorbed by cytochrome C oxidase chromophores within the mitochondria, endogenous protophyrins and melanin causing a downstream alteration that manifest in changes in cellular proliferation, differentiation, migration, inflammation or collagen production.7,9

EFFICACY OF LED

Various studies have demonstrated acceleration in wound healing with a dramatic reduction in inflammation. The use of red and NIR LLED wavelengths dramatically increased mitochondrial activity and subsequently increased ATP; an increase in fibroblast activity with resultant increase in collagen, enhanced epithelialisation and angiogenesis.9,10 Whelan et al (2001) reported an increase in fibroblast cell growth of 150-200% in treated areas vs untreated areas.5 A study conducted by Spitler and Berns (2014) using red (652nm) and NIR (806nm) showed significant enhanced activity in all cell types 24 hours post-exposure as well as improved cell migration.11

In chronic wounds with tissue ischaemia, Taradaj et al (2018) in their study on pressure ulcers identified a significant improvement in wound healing at 658nm.12 They also identified a significant reduction in concentration of interleukins, demonstrating a strong anti-inflammatory effect. Wound biopsies identified the elimination of the inflammatory reaction after two weeks’ exposure, significant increase in growth factors and angiogenesis in the same time frame. These results were supported in a study by Zhang et al (2018) in the management of radioactive dermatitis in cancer patients.13

The need for care of a population with wounds is a growing challenge that requires innovative strategies. The use and application of LED therapy at defined wavelengths in wound management has been proven to be a simple, cost-effective tool to help accelerate wound healing and significantly shorten healing time. This not only reduces wound pain, but ensures a smooth progress of healing, thereby improving quality of life and reducing the fiscal impact on the healthcare system. Today’s advances in wrap-able, shapetaking LED devices permit ease of use and application of light therapy anywhere on the body.  

REFERENCES

1. Takeo M, Lee W and Ito M. 2015. Wound Healing and Skin Regeneration. Cold Spring Harb Perpect Med. 5;5: 1-12.

2. Reinke J,M and Sorg H. 2012. Wound Repair and Regeneration. Eur Surg Res49: 35-43.

3. Sorg H, Tilkhorn D, J, Hagar S, Hauser J and Mirastschijski U. 2017. Eur Surg Res. 58: 81-94.

4. Guo S and DiPietro L,A. 2010. Factors Affecting Wound Healing. J Dent Re. 89 (3) 219-229.

5. Whelan H,T, Smits R,L, Buchman E, V, Whelan N,T, Turner S, G, Margolis D,A, Cevenini V, Stinson H, Ignatius R, Martin T, CWIKLINSKI J, Philippi A,F, Graf W,R, Hodgson B, Gould,L, Kane M, Chen G and Caviness J. 2001. Effect if NASA Light-Emitting Diode Irradiation on Wound Healing. Journal of Clinical Laser Medicine and Surgery. 19 (6) 305-314.

6. Velnar T and Gradisnik L. 2018. Tissue Augmentation in Wound Healing: The Role of Endothelial and Epithelial Cells. Med Arch 72 (6): 444-448.

7. Chavas M,E, de Aragujo A, Piancastelli A,C,C and Pinotti M. 2014. Effects of lowpower light therapy on wound healing: LASER x LED. An Bras Dermatol 89 (4) 616-623.

8. Avci P, Gupta A, Sedasivum M, Vecchio D, Pam Z, Pam N and Hamblin M.R. 2013. Low-Level Laser (light) Therapy (LLLT) in Skin: Stimulating, Healing, Restoring.

Semin Cutan Med Surg 32: 41-52.

9. Jagdeo J, Austin E, Mamalis A, Wong C, Ho D and Siegal D,M. 2018. Light -Emitting Diodes in Dermatology: A Systemic Review of Randomised Controlled Trials. Lasers in Surgery and Medicine. 50: 613-628

10. Rohringer S, Hointhoner W, Chudary, Siezak P, Priglinger E, Strassi M, Pill K, Muhleder S, Redi H and Dungei P. 2016. The impact of wavelengths of LED lighttherapy on endothelial cells. Scientific reports 7:10700

11. Spitier R and Berns M,W. 2014. Comaprison of laser and diode sources for acceleration of in vitro wound healing by low-level light therapy. Journal of Biomedical Optics. 19 (3): 1-9.

12. Taradaj J, Shay B, Drymarek R, Sopel M, Walewicz, Beeckman D, Schoonhoven L, Gefen A and Rosinczuk J. 2018. Effect of laser therapy on expression of angio and fibrogenic factors, and cytokine concentrations during the healing process of human pressure ulcers. International Journal of Medical Sciences. 15 (11) 1105-1112.

13. Zhang X, Li H, Li Q, Li C, Zhu M, Zhao B and Li G. 2018. Application of red-light phototherapy in the treatment of radioactive dermatitis in patients with head and neck cancer. World Journal of Surgical Oncology. 16: 222 1-8.

14. Barolet D 2008. Light-Emitting Diodes (LEDs) in Dermatology. Semin Cutan Med Surg. 27: 227-238.