Zinc-coated Foam With Negative Pressure Wound Therapy in the Treatment of Challenging Wounds: A New Alternative Interface Material

Objective. The aim of the study was to present the authors’ clinical observations on zinc-coated foam with negative pressure wound therapy (NPWT). Materials and Methods. Ninety-four consecutive patients treated with zinc-coated foam with VAC therapy were retrospectively reviewed. Nonhealing wounds of at least 6 months duration with high to moderate exudate that required open wound management to secondary intervention were included in this study. The evaluation criteria consisted of the measurement of wound surface area, length of overall treatment time, and a clinical observation of granulation tissue formation in the wound bed. Results. In all wounds, there was a significant decrease of the wound surface area, and wound exudate was obtained at the end of the treatment. There was a statistically significant difference between pretreatment and posttreatment measurements (P < 0.05). In all wounds, granulation tissue formation was clinically observed by day 6. Of the 94 wounds, 72 were surgically closed and 22 healed secondarily. The follow-up period averaged 12 months, and it was uneventful with no sign of complications from the use of the material. Conclusion. The results of the retrospective study demonstrate zinc-coated foam with NPWT can be safely used as an effective and alternative interface material in the treatment of challenging wounds. 

Zinc plays an essential role in immune function, antioxidant defense mechanism, and wound healing.^1,2 It has been shown that reepithelialization might be delayed by zinc deficiency,³ which can increase the time for wound closure and decrease wound strength.^4,5 This effect can be reversed by the use of a zinc-based adhesive dressing.¹ In addition, zinc has been used as a topical agent to treat diaper rash and as a nutritional supplement in patients with bedsores, ulcers, and incisional wounds.^6-9 In the form of a semi-adhesive tape, zinc was also found to be extremely useful in the treatment of partial-thickness burns.¹ Although the role of zinc in wound healing has been investigated since the 1950s, the mechanisms by which zinc affects healing processes are not clear.⁵

Negative pressure wound therapy (NPWT) is commonly used in prospective or retrospective clinical and experimental studies, and it is well known that it promotes wound healing in acute and chronic challenging wounds.^10,11 This therapy provides a moist wound-healing environment, increases granulation tissue formation, removes edema, and stimulates angiogenesis and blood flow to the wound margins.^12,13 The prime mechanism of NPWT essentially depends on its microdeformation effect on the wound bed that directly stimulates dermal cell proliferation and promotes healthy granulation tissue formation and vascular remodeling in living skin.^14,15 

Polyurethane foam and antimicrobial gauze are commonly used interface materials with NPWT since its first years of use in general practice. In addition, various numbers of clinical and experimental studies with different alternative interface materials such as a loofah sponge or silver-impregnated foam have also been documented in the literature.^15,16 In the literature, Günal et al¹⁶ have suggested additional materials coating the foam, such as silver, can contribute to faster bacterial clearance and healing times in the management of challenging, difficult-to-heal wounds.  

Zinc-coated foam as an interface material with NPWT was first introduced to the authors’ institution in 2012, and they observed significantly improved outcomes by using this material in the treatment of chronic, nonhealing, or acute wounds. In order to present these observations, the authors conducted a preliminary, noncomparative study to share the results of using this material in the management of wounds from different etiologies. Consequently, the objective of this study was to verify the efficacy of zinc-coated foam as an interface material with NPWT in various challenging wounds. 

The study retrospectively reviewed 94 patients treated with zinc-coated foam in conjunction with NPWT between 2013 and 2015. The study includes data collected from patient files of nonhealing wounds that lasted for at least 6 months with high to moderate exudate and required open wound management to secondary intervention. All patients signed the written informed consent form. The wound etiologies included pressure ulcer, diabetic foot ulcer (DFU), venous leg ulcer (VLU), and traumatic wound (Table 1). The evaluation criteria included measurements of wound surface area, duration of treatment, and length of time of granulation tissue formation in the wound bed. Before initiation of NPWT, debridement of necrotic and/or infected tissue was performed in the operating room when indicated (Figures 1, 2). In some cases, serial debridement was necessary. Negative pressure wound therapy was generally delayed for a few days until achieving postoperative homeostasis. The patients were administered antibiotics and analgesics when required. The negative pressure pump was set to continuously provide 125 mm Hg of negative pressure for the first 48 hours (Figure 3). After this period, dressing changes were consecutively performed at 48-hour intervals with intermittent 80 mm Hg to 100 mm Hg of negative pressure. Treatment was stopped when there was a sufficient and healthy granulation tissue formation, the wound had considerately decreased in size, and exudate had decreased (Figures 4, 5, 6, 7). Once NPWT was completed, the wounds were either covered by using different plastic surgical methods or left to heal secondarily (Figures 8, 9). Patients who could not be operated on due to risks of general anesthesia or with wounds less than 5 cm² at the end of the treatment were followed by secondary healing. Data were collected on patient demographics, wound type, duration of NPWT, and measurement of wound dimensions. 

Statistical Analysis
The Kolmogorov-Smirnov test was used to evaluate whether the distribution of variables was normal. Accordingly, the study found all variables displayed a normal distribution. Because many groups had small sample sizes, nonparametric methods were used for statistical comparisons. The Kruskal-Wallis test was used to compare the wound areas among groups and the Bonferroni-corrected Mann-Whitney test was used for post hoc analysis of the pairwise groups. The Wilcoxon rank sum test was used to compare the 2 periods for each group and Spearman rank correlation was performed to determine the relationship between length of treatment and shrinkage of wound area. Wound areas and other numerical data are presented as mean ± standard deviation. Pearson’s chi-square test was used to compare the categorical data among groups. Categorical variables were presented as count and percentages. A P value < 0.05 was considered statistically significant. Analyses were performed using commercial software (SPSS Version 23; IBM, Armonk, NY).

Table 1 presents demographic features of the patients according to wound etiology and pretreatment and posttreatment alterations. The wounds studied were pressure ulcers (PUs) (33 cases), DFUs (35 cases), VLUs (15 cases), and traumatic wounds (11 cases). In the majority of the wounds, a significant decrease of the wound areas and exudate were achieved by the end of treatment. Regarding the decrease in wound surface area, there was a statistically significant difference in all wound types between pretreatment and posttreatment measurements (P < 0.001, Table 2). In the pretreatment period, average wound size was 65.29 ± 49.42 cm² in DFUs, 50.6 ± 52.08 cm² in VLUs, 59.45 ± 28.95 cm² in traumatic wounds, 124.07 ± 96.52 cm² in ischial PUs, 94.29 ± 41.68 cm² in sacral PUs, and 65.91 ± 25.86 cm² in trochanteric PUs. In the posttreatment period, the measurements were 26.23 ± 26.09 cm² in DFUs, 16.53 ± 16.68 cm² in VLUs, 31.14 ± 22.51 cm² in traumatic wounds, 65.93 ± 64.36 cm² in ischial PUs, 44.57 ± 29.69 cm² in sacral PUs, and 28.73 ± 17.13 cm² in trochanteric PUs. The average total application time was 13.97 ± 3.97 days in DFUs, 12.93 ± 2.43 days in VLUs, 14 ± 2.45 days in traumatic wounds, 15.47 ± 3.58 days in ischial PUs, 13.57 ± 3.05 days in sacral PUs, and 19 ± 9.8 days in trochanteric PUs. A healthy granulation tissue formation was clinically observed by day 6 in the wounds. Seventy-two wounds were surgically closed using different plastic surgical methods and there was no considerable skin graft loss or flap failure in the follow-up period. The remaining 22 wounds were left to secondary healing. Eighteen  of the remaining wounds, which were already less than 5 cm² at the end of treatment, completely healed secondarily in the follow-up period. The other 4 cases, which were 5 cm² to 10 cm² in wound surface area in the same period, could not be given general anesthesia due to contraindications. These wounds were also uneventful in the follow-up period. 

Negative pressure wound therapy is known to have beneficial effects in PUs, VLUs, skin grafts, sternal and abdominal wounds, traumatic injuries, and lymphorrhea.^14-20 However, alternative interface materials such as foam, gauze, silver-coated foam, and negative pump devices have been investigated in the literature.^14-16 In NPWT, the pressure delivered to the wound bed by a suction tube and wound filler, gauze, or foam, creates the mechanical stress on the surface of the wound. Negative pressure wound therapy has been shown to significantly increase the expression of intercellular adhesion molecule 1, migration inhibitory factor, vascular endothelial growth factor, and collagen I level.¹³ The other effect of negative pressure is the elimination of proteases, which inhibits wound healing.²¹ Thus, NPWT removes excess interstitial space fluid and promotes better capillary circulation, increases vascularity of the wound and granulation tissue formation, and reduces wound size.²² In some cases, complete closure can even be achieved. 

The majority of literature suggests NPWT decreases the hospitalization and treatment times of patients with acute or chronic wounds by an average of 2 weeks compared with that of the traditional saline gauze dressings.^23-27 In the present study, the average length of NPWT was 14.82 days to secondary closure, with the use of zinc-coated foam as an interface material. Granulation tissue was clinically noted in all wounds by day 6. In a similar study of 75 patients with open wounds in the lower extremity, granulation tissue was present by day 4 of NPWT, with decreased edema and bacterial counts.²⁸ In a study made in 21 consecutive patients with high-energy soft-tissue wounds who underwent NPWT, the treatment time was an average of 19.3 days.²⁹ In another study, the duration of NPWT averaged 10 days to primary closure and 17 days to secondary closure. Granulation tissue formation was noted in all patients by day 4.³⁰ The authors believe the study results are comparable to other studies^28-30; however, a comparative study is needed to suggest whether zinc-coated foam is superior to or more effective than traditional foam with NPWT in decreasing hospitalization time, allowing for earlier rehabilitation of the patients, and providing faster and healthier granulation tissue formation.

To the authors’ knowledge, the present study is the first to report the use of NPWT in conjunction with zinc-coated foam. Zinc-based dressings have been used in treating VLUs³¹ and burns where it was absorbed into the granulation tissue.³² Zinc is absorbed from the semiadhesive tape into the pancreas, bone, hair, and skin in rats³²; it probably acts at the wound site and is incorporated into enzyme systems, which play a role in protein synthesis and cellular metabolism.¹ In an experimental study, local administration of zinc was suggested to increase cell proliferation, causing increased growth factor production which yields improved chondrogenesis and endochondral ossification, leading to accelerated fracture healing as early as 4 weeks postfracture.³³ Local injection of long-acting insulin-zinc suspension was shown to accelerate skin wound healing without major systemic side effects, demonstrating its potential usefulness in burn treatments.³⁴ According to a study of different administration methods, topical application of zinc was found to be superior to oral therapy due to its action in reducing superinfections and necrotic material via enhanced local defense systems and collagenolytic activity, as well as the sustained release of zinc ions that stimulate epithelialization of wounds in normozincemic individuals.³⁵ Topical zinc therapy is underutilized even though clinical evidence emphasizes its importance in autodebridement, anti-infective action, and promotion of epithelialization.³⁵ In an experimental study of rats with diabetes,³⁶ topical zinc therapy used on full-thickness wounds was found to decrease bacterial growth. Although mechanisms are not fully known, application of zinc has been shown to accelerate the healing of both chronic and acute wounds.^37,38 Further, the literature shows the increased gene expression of insulin-like growth factor-1 may be another mechanism by which topical zinc oxide enhances wound healing.^37,38 Zinc therapy was shown to have a role for many physiological processes, including gene transcription, phagocytic activity of macrophages, and stabilization of biological membranes.³⁹ Zinc is also a modulator of the wound-repair process.^40,41 Due to its antioxidant and anti-inflammatory properties, it has been used in the treatment of psoriasis, hair loss, VLUs, and partial-thickness burn wounds.^39,42 An experimental study reported that when the zinc level increases to 15% to 20% at the margin of the wound in the first 24 hours, the epidermal proliferation and granulation tissue are at the maximum level.^43,44 It was suggested that topical application of zinc decreases the rate of debris and necrotic material and increases epithelialization.⁴¹ Studies^45,46 show zinc has antibacterial and antiviral activity, which means it can decrease bacterial load and wound necrosis in wound healing. Based on the authors’ study, it can be speculated that using zinc-coated foam in conjunction with NPWT therapy can have a synergistic effect in wound healing.

The rationale of the present study is zinc in combination with NPWT therapy can have beneficial effects on wound healing when applied to open wounds or the wounds needing delayed primary closure. The study presents a relatively large number of wounds of varying sizes and from different etiologies; however, the limitations include that the study is not comparative and prospective. The majority of wounds showed considerable decreases in wound area measurements and decreased exudates at the end of treatment. Regarding these findings, statistically significant difference was found in all wound types between pretreatment and posttreatment measurements. In addition, the decrease of the treatment and hospitalization time was comparable to that of other similar studies in the literature. According to this study’s results, the method was more successful in DFUs and VLUs. However, these wounds were partial-thickness and relatively small compared to others in the pretreatment period. In this study, the authors also observed a relatively reduced necessity for soft-tissue transposition as compared to the results of the authors’ previously published studies^14,16 using gauze-based and silver-coated foam interface materials.^14,16 With the use of zinc-coated foam and NPWT therapy, 72 of the 94 patients required surgical interventions for soft tissue coverage and the remaining 22 healed secondarily. Of these 22 wounds, 18 were intentionally left to secondary healing because these were already less than 5 cm² at the end of the treatment, whereas the other 4 were 5 cm² to 10 cm² in diameter in the same period, and general anesthesia could not be administered to these patients due to contraindications. According to these findings, the authors believe topical zinc might actually have provided additional contributions to the wound healing. Any adverse effect of using zinc was not observed in the treatment or follow-up period. The present method may also be preferable for infected or challenging wounds which do not respond to other treatment methods. The relatively long treatment period can be attributed to the challenging wounds in this study. 

The efficacy of zinc and NPWT therapy in chronic or acute wounds has been documented in the literature, but there is no evidence of studies related to their combined use. This study’s authors found the use of zinc-coated foam with NPWT to be an effective and alternative method in the management of challenging wounds; however, comparative clinical and experimental studies should be planned to further determine the benefit or contribution of zinc in the treatment of challenging wounds.

Affiliations: Samsun Education and Research Hospital, Department of Plastic Reconstructive and Aesthetic Surgery, Samsun, Turkey; Samsun State Hospital, Department of Plastic Reconstructive and Aesthetic Surgery, Samsun, Turkey; Tokat State Hospital, Department of Plastic Reconstructive and Aesthetic Surgery, Tokat, Turkey; and Sakarya University, Faculty of Medicine, Department of Biostatistics, Sakarya, Turkey

Correspondence:
Umut Tuncel, MD
Department of Plastic Reconstructive and Aesthetic Surgery
Samsun Education and Research Hospital
55100, Samsun, Turkey
drumuttuncel@gmail.com

Disclosure: The authors disclose no financial or other conflicts of interest.