Appropriate wound management is a crucial concern in surgical patients because the failure of wounds to heal is associated with profound morbidity, impaired quality of life, and significant economic costs [12]. Therefore, surgeons should become actively involved in wound care to optimize the environment in which a wound can heal. Systematic care, such as the correction of medical comorbidities, improvement of nutritional status, or surgical debridement of infected wounds, should be undertaken in accordance with the proper use of dressings to facilitate optimal healing.

An ideal wound dressing would allow adequate gaseous exchange, maintain a moist environment while preventing maceration, allow drainage and absorption of exudates, protect the wound from trauma and infection, facilitate debridement, minimize scarring, and be nonadherent during dressing changes, thereby minimizing trauma and pain. Other practical considerations include cost, availability, and stability in storage and use [34].

Conventional gauze dressings work on the basis of forming a dry, protective barrier that can prevent bacterial contamination and absorb exudate. In the 1950s, a new concept for wound management was introduced that promoted moist wound healing to greatly increase re-epithelialization. This method was aimed at occluding the wound to protect it against bacteria while keeping it moist to supply growth factors and prevent crust formation, which would impede wound healing. Since then, a huge variety of products have been developed and used for all types of wounds. These include semipermeable films, hydrogel, alginate, hydrofiber, hydrocolloid, foam, and nonadherent contact [56].

Foam dressings are made of polyurethane or silicone, which enables them to handle large volumes of wound fluid. They are indicated for wounds with moderate to high levels of exudates and across a range of wound characteristics. To be used for complicated, infected, or anticipated infected wounds, local antiseptic treatment should be addressed. Silver, in forms such as silver nitrate and silver sulfadiazine, has been used as a topical antimicrobial agent for controlling colonization. Silver-containing foam dressings are now broadly used because they also have broad-spectrum antimicrobial properties. However, the concern with this type of dressing material is cytotoxicity and resistance to the dressing's antimicrobial properties [78].

A newly developed polyurethane foam dressing impregnated with 3% povidone-iodine (PI) (Betafoam, Genewel, Seongnam, Korea) achieves powerful antimicrobial properties while also providing a moist environment. PI is a common antimicrobial agent and has been used as a surgical scrub or a skin cleanser in various forms. Although PI has long been used in its different forms because it has good antimicrobial properties, the efficacy of foam dressings with PI has not been confirmed.

In this study, therefore, we evaluated the efficacy of Betafoam in terms of wound healing and safety by comparison with several silver-containing foam dressings in an animal model.

Optimal wound management requires the selection of the most appropriate dressing. The primary focus for wound care is eliminating causative factors such as pressure, shear, moisture, and circulatory impairment; providing systemic support instead of scrubbing wounds; and leaving wounds open to the air [48]. Among the various types of dressing materials, foam dressings are most commonly used for good exudate management and shielding from bacterial invasion. Foam in various forms has been widely used for the management of many types of wounds. A large number of clinical results have been published that describe the effectiveness of foam in surgical wounds. Clinical experience from these studies suggests that foam dressings are easy to apply, relatively painless to remove, and therefore preferred by patients and surgeons alike. By their very nature, foam dressings give opportunities to act as carriers for antimicrobial agents, and many kinds of foam dressings that contain silver or other bactericidal agents are available.

Thus far, silver-containing foam dressings have been commonly used for healing wounds, including burns, diabetic ulcers, and surgical wounds. Clinical experience has proved the antibacterial effects of such dressings and, consequently, silver has been used in a variety of dressings in various forms and contents. However, several studies have reported side effects related to silver; in particular, one study demonstrated that silver had cytotoxic effects at the wound site, became deposited in the organs, and inhibited the proliferation of human fibroblasts, thus delaying wound healing [10]. There has also been some concern regarding the use of silver dressings because reactive oxygen species induced by silver are highly reactive and cause oxidative DNA damage and inflammation [111213].

Furthermore, there has been concern that the use of silver dressings may lead to bacterial resistance to antibiotics and silver itself [11]. Therefore, the benefits of the antimicrobial actions of dressing materials need to be carefully balanced against the cytotoxic effects and bacterial resistance that silver can produce.

PI is a commonly used antimicrobial agent. It is a water-soluble complex with elemental iodine bound to a synthetic polymer. It is also a bactericide that can be applied as a paint, spray, or wet soak for various types of wounds including burns, abrasions, lacerations, skin infections, and pressure sores. The basis of its recent development was the premise that the antimicrobial activity of PI was as good as that of current silver-containing foam dressings but was also associated with reduced cost and cytotoxicity. Although the current literature concerning the cytotoxicity of PI is conflicting, some studies have demonstrated improved wound healing through the use of PI [1213].

The current study showed that Betafoam was the most effective dressing in terms of wound healing and re-epithelialization compared with the various silver-containing foams and the gauze. Wound healing process models including hemostasis, inflammation, proliferation and remodeling, have considerable overlapping phase and re-epithelialization of wounds begins within hours after injury. So we thought that 7 days results would be considerable to evaluate the epithelialization status. Although the wound size generally decreased over time in all groups, the Betafoam group showed the most notable decrease in the size of the cut wound, and the difference between the Betafoam and the other groups was statistically significant on day 14. Also, significant differences were found between Betafoam N and gauze groups on days 7 and 10 (P < 0.05) (Fig. 3B). Levenson et al. [14] demonstrated that the great bulk of collagen formation and gain in tensile strength of healing skin incision is over in the first 2 or 3 weeks, and that the wound reaches its maximal strength at the end of this time. It might be related with fibroplasia, occurring during the first 14 days postoperatively.

After 7 days, re-epithelialization was greater in Betafoam in Fig. 3, however in Fig. 2, wound area was not correlated with the result of re-epithelialization. This discrepancy might come from that re-epithelialization (%) was calculated microscopically, and wound area was analyzed grossly. In terms of re-epithelialization, polyurethane foam dressing has the advantages of stimulating re-epithelialization by enhancing epithelial cell movement and absorbing exudates from the wound [5]. Bennett et al. [13] concluded that PI cream was statistically superior to silver sulfadiazine with regard to the healing of experimental wounds. Consistent with these results, our data demonstrated a significant difference in re-epithelialization between Betafoam and other dressings.

Neovascularization is another important process that takes place during wound healing. The H&E staining also highlighted the capillary network and collagen deposition at the wound edge during the experimental periods. These outcomes demonstrated that the number of blood vessels in the Betafoam group was significantly higher than in the other groups. An in vivo comparison of topical agents on wound repair conducted by Bennett et al. [13] demonstrated that PI cream significantly enhanced angiogenesis compared with other topical agents, including silver. In addition, collagen deposition in the Betafoam group increased to a significantly greater degree than in the other groups. Thus, although the mechanism is still unclear, PI has been proven most effective in collagen deposition while concomitantly increasing angiogenesis.

During dressing changes, minimal mechanical trauma should be inflicted when cleansing wounds because additional trauma to the wound base delays wound healing. Disturbance of the wound base should be minimized not only to avoid additional tissue damage, but also to eliminate unexpected discomfort for the patient and to minimize the spread of microorganisms. To evaluate tissue damage caused during dressing changes, the amount of residual DNA remaining in the dressing materials was measured on days 3, 7, 10, and 14. The results showed that the Betafoam group had less severe tissue separation than any other group.

This study has some limitation. We did not take the inflammatory phase into account in this study. Some may argue that the experimental wound healing model is for the second wound closure, and does not well represent the primary wound repair nor infected wound repair. But we focused basic wound healing characteristics of Betafoam N and further evaluation is needed to evaluated antimicrobial effect for infected wound. We think that partial or full thickness burn wound, pressure sore, diabetic ulcer and chronic venous ulceration could be the best candidate for this material. Also primary surgical wound could benefit from this material for preventing wound infection.

In conclusion, this is the first experimental in vivo study to compare Betafoam and other dressing materials, with a particular focus on full-thickness skin wounds. Our data showed that Betafoam is effective in wound healing and performs best in re-epithelialization, angiogenesis, collagen deposition, and tissue invasion among the various types of dressing materials.