Promoting Surgical Wound Healing Through Small Molecule Nutrition Featuring Plant-Derived Biologics

In our continued series on skin care in the wound clinic, this article discusses the utilization of wound healing products containing small molecule nutrients, including those offering plant-derived biologics, to promote rapid healing and to decrease risk of infection following surgery. 

Each year, approximately 200 million surgical procedures are performed globally,¹ with 80 million surgeries carried out in the United States.² Serious complications can occur following surgical procedures, including surgical site infections (SSIs) that contribute substantially to the morbidity and mortality associated with surgery.^3,4 In fact, SSIs occur in up to 30% of all surgeries.¹ Impaired wound healing following surgery can increase the risk of SSIs. This article will discuss the utilization of wound healing products containing small molecule nutrients, including those offering plant-derived biologics, to promote more rapid wound healing and to decrease risk of serious infection following surgical procedures.

Acknowledging Risks Post-Surgery 

Wound healing involves four critical phases that overlap: the coagulation phase, the inflammatory phase, the migration-proliferation phase (development of granulation tissue), and the remodeling-regeneration phase that includes maturation, scar formation, and reepithelialization. The goal of surgical wound healing is to avoid edema, infection, separation of wound edges (dehiscence), and excessive scarring. Surgical wounds heal by primary intention, delayed primary intention, or secondary intention. However, the majority of surgical wounds heal by primary intention, in which the wound edges are brought together and kept in place by adhesive strips, staples, or sutures. Delayed primary intention or secondary intention healing occurs when wounds are left open temporarily or until the wound is completely healed, respectively.⁵ The magnitude of the inflammation phase affects the amount of scar tissue produced at the conclusion of the healing process.^6,7 Factors that can contribute to impaired wound healing include diabetes, cancer, vascular disease, aging, stress, obesity, smoking, alcohol use, certain medications, treatments such as chemotherapy, decreased circulation, and infections.^8,9 Providing nutrients to the skin to help improve wound healing is critical. In fact, plant-derived biologics, as well as other biologics, have proven to be very beneficial. Impaired skin nutrition decreases skin integrity and functioning,  as well as wound healing capability.^8,10 In addition, skin irritation and prolonged oxidative stress and inflammation can lead to impaired wound healing.¹¹ 

Impaired wound healing can increase the risk of SSIs, defined as infections that occur at or near a surgical incision within 30 days of the procedure.¹² SSIs occur in 2-14% of all surgical patients post-discharge due in part to shorter hospitalizations.^13,14 More than half of those patients who develop post-discharge SSIs are readmitted to the hospital.¹⁴ In fact, with an annual financial impact of more than $3 billion dollars nationally, SSIs are now the most costly healthcare-associated infections.¹⁵ Staphylococcus aureus is the most common cause of SSIs,¹⁶ many of which occur slowly post-discharge, possibly due to the development of biofilms,¹⁷ or aggregates of bacteria (or other microorganisms) enclosed in a protective matrix that strongly adhere to surfaces such as skin tissues.¹⁸ Bacterial biofilms that have developed over a period of seven days or more are resistant to 500-5,000 times the concentration of antibiotics required to kill the same free-growing bacteria.¹⁶ 

Improving Wound Outcomes Through Biological Skin Nutrition  

Topical small molecule technology (found in AtHome^™ Viniferamine^® skin and wound care products, McCord Research, Coralville, IA) that provides penetrating nutrition to skin has produced documented wound healing outcomes in the outpatient setting for those patients who will require continued skin and wound care at home. The AtHome Edema Skin Care kits also include products and educational materials to help patients decrease edema and edema-associated skin problems. Containing vital skin nutrients that help decrease the risk of surgical wound complications, these products also include various ingredients that counteract oxidative stress: the important small molecule polyphenols oleuropein, resveratrol, and epigallocatechin-3-gallate (EGCG) from olives, grapes, and green tea, respectively, and L-carnosine, melatonin, and L-glutathione.^19-24 Several of these ingredients also decrease inflammation, including oleuropein, resveratrol, EGCG, melatonin, carnosine, and L-glutathione.^{19,21,22,25-27} Moreover, asiaticoside in titrated extracts of Centella asiatica, dipotassium glycyrrhizate from licorice, avenanthramides in oats, aloe vera, panthenol, and shea butter possess anti-inflammatory activities.^28-33 Many ingredients improve wound healing. Particularly, oleuropein has been shown to improve wound healing in an aging model,³⁴ resveratrol has been shown to improve wound healing in individuals living with type 2 diabetes,³⁵ EGCG was found to accelerate keratinocyte differentiation and wound healing,³⁶ and melatonin was found to accelerate the process of wound repair in full-thickness incisional wounds.³⁷ In addition, L-carnosine was found to stimulate wound healing in an incision wound model³⁸ and L-glutathione was shown to be beneficial for ischemic wound healing.²⁴ Furthermore, C. asiatica³⁹ and one of its main components, asiaticoside,⁴⁰ have important wound healing activities while dipotassium glycyrrhizate is known to protect hyaluronic acid,⁴¹ which plays an important role in wound healing.⁴² 

Several of the ingredients found in these products also have antimicrobial effects, including action against biofilms. Resveratrol has been reported to inhibit methicillin-resistant S. aureus (MRSA) biofilms.⁴³ EGCG was shown to have antimicrobial effects against Pseudomonas aeruginosa ⁴⁴ and S. aureus that included activities against biofilm formation.⁴⁵ EGCG has been shown to disrupt the communication signaling required for Escherichia coli to form biofilms.⁴⁶ Oleuropein has been shown to inhibit the growth of several bacterial strains including S. aureus.⁴⁷ Melatonin has antimicrobial effects against MRSA and antibiotic-resistant P. aeruginosa⁴⁸ as well. Chlorhexidine digluconate, a component of the Viniferamine Silicone Barrier product that’s included in the AtHome Edema Skin Care kit, has been shown to prevent wound contamination,⁴⁹ to be effective against vancomycin-resistant Enterococcus faecium, and to be utilized to cleanse patients in the intensive care unit.⁵⁰ Moreover, chlorhexidine digluconate has been found effective against Streptococcus epidermidis, including in biofilms.⁵¹ In the case of delayed, open primary or secondary surgical wounds, hydrogels have been used to promote healing.⁵² Viniferamine Wound Hydrogel Ag contains a medical-grade silver, an effective antimicrobial against gram-positive MRSA, in addition to various gram-negative bacteria including P. aeruginosa and E. coli.^53,54

Effects On Excessive Scarring 

Besides infection, excessive scarring is another potentially serious complication of surgical wound healing.⁵⁵ Scars are areas of dermal fibrosis that replace normal tissue after injury and during wound healing.⁵⁶ There are two types of excessive dermal scars: hypertrophic scars that are characterized by raised areas of skin and keloid scars characterized by growth outside the original wound area. The transformation of a coagulated wound into granulation tissue requires a critical balance between extracellular matrix protein deposition and degradation. If this process is disrupted, abnormalities in scarring may occur, resulting in excessive scarring.^57,58 Scars can be disfiguring and may cause severe itching, tenderness, pain, sleep disturbance, and anxiety, particularly in the case of keloid scars or hypertrophic scars^59,60 that are likely caused by the dysregulation of collagen synthesis.⁵⁶ Scar tissue is composed mostly of myofibroblasts — disorganized collagen-rich extracellular matrix produced by skin cells that are stimulated by the signaling molecule (cytokine) transforming growth factor beta 1 (TGF-β1). Typically, myofibroblasts are programmed to die in a process called apoptosis, which leaves a normal scar; however, in some pathological conditions, these cells fail to undergo cell death and persist, as in the case of excessive scarring.⁶¹ Various ingredients in the products have activities against excessive scarring. Resveratrol has been shown to inhibit growth and induce apoptosis in keloid fibroblasts. In addition, resveratrol decreases human keloid fibroblast production of TGF-β1, suggesting that resveratrol may help in the treatment of keloids.⁶² Furthermore, resveratrol has been shown to reduce collagen production in human hypertrophic scar fibroblasts by inhibiting proliferation and inducing apoptosis.⁶³ EGCG has been shown to decrease collagen expression in human keloid fibroblasts and attenuate the TGF-β1-induced differentiation of myofibroblasts,^64,65 suggesting that EGCG may also have a role in improving wound healing and scarring. In addition, asiaticoside has been shown to reduce scarring and decrease TGF-β1expression in a model of hypertrophic scarring. Asiaticoside was shown to suppress collagen expression and TGF-β1 signaling in human keloid fibroblasts and in a model of hypertrophic scarring.^66,67 Hydration is important for reducing scarring because it restores homeostasis to the scar, reducing collagen deposition and excessive scar formation.⁶⁸ Aloe vera promotes skin hydration by increasing levels of hyaluronic acid, which has a high capacity for retaining water.^69,70 Hyaluronic acid has also been shown to reduce dermal scarring. In addition, one of the most consistently successful hydrating agents used in scar management has been silicone in dimethicone topical applications.⁶⁸ Silicone Barrier contains dipotassium glycyrrhizate, aloe vera, and dimethicone to improve and maintain skin hydration and to help decrease scarring.

Conclusion

Surgical procedures can result in complications including SSIs, edema, and excessive scarring. Understanding how specialized ingredients that include small molecule nutrients can promote healing and help decrease complications can aid wound care clinicians in adapting care plans. AtHome Viniferamine Edema Skin Care can be a determining factor in avoiding skin problems associated with edema. In addition, the many beneficial ingredients with antimicrobial activity contained in Silicone Barrier, including chlorhexidine digluconate, can help decrease risk of SSIs. Various ingredients can also help decrease excessive scarring. Viniferamine Wound Hydrogel Ag can be beneficial for healing open surgical wounds. Overall, Viniferamine skin and wound care can be an effective method to continue care plans across different settings. 

D. Elizabeth McCord, senior researcher at McCord Research, Coralville, IA, is a renowned biochemist in the field of skin and wound care. She has been awarded six patents and two medical devices, and has more than 60 health products marketed globally. She previously commercialized wound and skin care products under the Remedy^® Olivamine^® brand. Kyle D. Hilsabeck is vice president of pharmaceutical affairs at McCord Holdings and licensed by the Iowa Board of Pharmacy. He completed bachelor’s degrees in biology and biochemistry at Wartburg College, and his doctorate at the University of Iowa College of Pharmacy. He completed a community pharmacy residency through the University of Iowa and taught for the University of Iowa College of Pharmacy. Nancy B. Ray is science officer at McCord Research. She currently writes and presents on diabetes, skin care, and other topics to advance skin care and wound healing awareness. She received her PhD in biochemistry and biophysics at Oregon State University and was a postdoctoral fellow at the National Institutes of Health, Harvard University, Dana-Farber Cancer Institute, and the University of Iowa. She also earned bachelor’s degrees in chemistry and microbiology from the University of Montana.

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