Can Zinc Oxide Have An Impact On Wound Healing?
As the complexity and price of wound care materials seems to be reaching mind-numbing proportions, choosing the right product for your patients seems to be getting harder instead of easier. However, taking into account cost, effectiveness and availability, one would be hard pressed to find a product better than zinc oxide. Although it is most commonly associated with diaper rash ointments and Unna boot wraps, zinc oxide has remained relatively underused in podiatry offices and in wound care centers. Considering that more than 300 enzymes are dependent on zinc for activity such as matrix metalloproteinases (MMPs), zinc oxide (which averages between $2 and $3 a tube) should be a product that is used more in treating wounds. Despite a very long history, zinc oxide is a uniquely modern material. Having a wide array of properties, it continues to increase in value in many of the ever-widening fields of science and technology: physics, chemistry, biology, electronics, industry, agriculture and wound healing. The favorable effects of zinc oxide (ZnO) were discovered almost accidentally during animal studies in the 1950s. Since that time, researchers have vigorously studied zinc with regard to its biochemical impact on healing. Not only does zinc play a role in metalloenzyme activity, it is also involved in nucleic acid and protein metabolism. In fact, zinc protrusions were recently found within large quantities in transcription factors that interact with the promoter region of DNA before a segment is transcribed into RNA coding for growth factors.1 What The Literature Reveals The beneficial effects of zinc in wound healing have been reported to explain the retarded wound repair response seen in zinc-deficient patients along with the normalization of the wound healing mechanisms with zinc therapy.2 In animal studies, zinc deficiency decreased the tensile strength of surgical wounds. This could also be explained by the fact that 20 percent of the body’s zinc is stored in the skin and is concentrated in the epithelium.3 In contrast to oral zinc, topical zinc appears to be beneficial regardless of zinc status. The increased demand for zinc during the wound healing process is satisfied for prolonged periods by applying zinc oxide to the wound. When zinc oxide is delivered, zinc ions stay within the wound fluid for an extended period of time, which results in constant wound tissue zinc levels.4 The ultimate effect of zinc oxide seems to be in the acceleration of re-epithelialization within the wound, yet most of the mechanisms are unknown. What has been clearly demonstrated, however, is that zinc oxide does have a positive impact on the wound. In a 1991 study, researchers found that using zinc oxide increased the degradation of collagen in necrotic wounds.5 In another recent study, zinc oxide was found to promote epithelialization of full thickness skin wounds by the activation of zinc-dependent MMPs, which facilitate keratinocyte migration. The study also demonstrated that zinc oxide augmented endogenous expression of insulin-like growth factor (IGF-1), which is fundamental in the production of granulation tissue.1 In a randomized, double-blind study of the efficacy of locally applied zinc oxide on the healing of leg ulcers, 37 geriatric patients (19 with arterial and 18 with venous leg ulcers) were treated with either a gauze compress medicated with zinc oxide or an identical compress without zinc oxide. The treatment was assessed from ulcer size measurements and the presence or absence of granulation, and ulcer debridement over a period of eight weeks. The zinc-treated patients (83 percent success rate) responded significantly better than the placebo-treated patients. Researchers found that infections and the deterioration of ulcers were less common in zinc oxide treated patients.6 In another animal study, reepithelialization was enhanced when zinc oxide was applied topically on partial-thickness wound in pigs with normal zinc status. The inflammatory reaction was diminished in zinc-treated wounds except when researchers applied a high zinc sulfate concentration.7 Researchers also assessed bacterial growth in full-thickness wounds and demonstrated a reduced rate of growth with topical zinc oxide but not in hyperglycemic diabetic rats. The antibacterial mechanism of zinc oxide was described to be more indirect (mediated via local defense systems) rather than being directly toxic to the bacteria.8 When one applies zinc on wounds, it not only corrects a local zinc deficit but also acts pharmacologically. Getting Results With Zinc Oxide: A Few Case Studies A 47-year-old type 2 diabetic patient presented to the office with a chronic grade 1-A (University of Texas Wound Classification System) ulceration that had been present on and off for over two years. After providing effective pressure relief and debridement, the patient was treated in the office and at home with zinc oxide. Within 14 days, the wound completely closed. A 58-year-old type 2 diabetic presented with a chronic interdigital ulceration that had been present for over a year. The ulceration was present secondary to a contracted digit and neuropathy. The patient’s wound healing was extremely poor from both non-compliance and poorly controlled blood sugar. Given the inflammatory and chronic nature of the wound, we started daily zinc oxide treatments along with regualr wound care. In less than 14 days, the patient had complete epithelialization of the wound (see photos on pages 22 and 25). A 63-year-old vascularly compromised diabetic type 2 patient presented to the office with a severe streptococcus infection throughout his entire left forefoot, resulting in significant skin loss dorsally and plantarly. A year earlier, the patient had a transmetatarsal amputation and a partial fifth ray amputation six months later on the left foot. After the patient had a brief hospital stay along with IV antibiotics, we began zinc oxide treatments immediately. We chose zinc because of its ease of use in the home and its excellent antiinflammatory and drying properties. Despite the patient’s poor vascular status and extremely poor home conditions, the patient used the zinc oxide faithfully and presented regularly for his in-office wound care, resulting in complete healing in a matter of three months. A 51-year-old diabetic patient developed a severe pin tract infection following a routine K-wire removal after a simple digital arthroplasty. The pin tract infection resulted in a cellulitic sausage digit deformity. While in the hospital for IV antibiotics, a minor incision and drainage was performed. After the procedure, daily zinc oxide treatments were started, resulting in complete resolution of the sausage digit deformity. Key Practical Considerations Practically, zinc oxide is an affordable option that even your most non-compliant patients can easily apply at home. By actively facilitating absorption of moisture and odors within the wound, indications for zinc oxide are broad, including: • post-inflammatory skin following surgery; • post-matrixectomy/nail surgery; • draining wounds; • venous/arterial ulcers (with compression); • interdigital wounds (does not cause maceration); • vesicular dermatitis (eczema/tinea pedis); • full thickness wounds; • partial thickness wounds; • heel fissures; and • puncture wounds. There are several commercially available products that have zinc oxide, including Dermagran wound cleanser/hydrogel/moisturizer, zinc paste bandages (Unna boot), Double Guard Skin Guard, Zinc Oxide adhering tape, Derma 50 and many diaper rash ointments. Keep in mind that zinc oxide must be used in conjunction with good overall wound care that includes but is not limited to debridement, compression (venous stasis ulcerations), appropriate offloading, antibiotics and surgical intervention. Final Notes Clinically, zinc oxide keeps wounds moist and clean while facilitating wound healing. After cleansing of the wound with saline (along with indicated debridement), one may apply zinc oxide onto the wound in a thick layer followed by a non-adherent dressing or gauze. Wounds are in constant evolution and though zinc oxide is an excellent and inexpensive tool for your armamentarium, keep in mind that wounds have different needs at different points in time. Dr. Moore is a former University of Texas Diabetic Foot Fellow who currently practices in Somerset, Ky. Dr. Steinberg (pictured) is an Assistant Professor in the Department of Orthopaedics/Podiatry Service at the University of Texas Health Science Center.
References 1. Agren, MS, Steenfos, HH. Zinc Oxide. EWWA Journal 2001, Vol. 1, No. 1. 2. Agren, MS. Studies on zinc in wound healing. Acta Derm Venerol Suppl (Stockh) 1990; 154:1-36. 3. Portes WJ, Henzel JH, Rob CG, et. al. Acceleration of wound healing in man with zinc sulfate given by mouth. Lancet 1967:21:121. 4. Agren, MS, Krusell M, Franzen L. Release and absorption of zinc from zinc oxide and zinc sulfate in open wounds. Acta Derm Venerol. 1991; 71(4):330-3. 5. Agren, MS. Zinc oxide increases degradation of collagen in necrotic wound tissue. Br J Dermatol. 1993 Aug;129(2):221. 6. Stromberg, HE, Agren MS. Topical zinc oxide treatment improves arterial and venous leg ulcers. Br J Dermatol 1984; 111:461-8. 7. Agren MS, Chvapil M, Franzen L. Enhancement of reepithelialization with topical zinc oxide in porcine partial-thickness wounds. J Surg Res. 1991 Feb;50(2):101-105. 8. Agren, MS, Soderberg TA, Reuterving CO, Hallmans G, Tengrup I. Effect of topical zinc oxide on bacterial growth and inflammation in full-thickness skin wounds in normal and diabetic rats. Eur J Surg. 1991 Feb;157(2):97-101.