Effect of Occlusion and Semi-occlusion on Experimental Skin Wound Healing: A Reevaluation

More than 1000 different occlusive dressings are commercially available.¹ Occlusion may enhance wound healing primarily through the prevention of wound desiccation.As a result, epidermal necrosis and eschar formation do not occur, and wounds reepithelialize more rapidly.^2–7 However, the benefits of occlusive wound dressings remain sub judice for some.^8–15 Some animal studies indicate that fully occlusive dressings may suppress barrier recovery and reduce the epidermal proliferative response to an abnormal stratum corneum barrier.^8–11 In addition, occlusion may increase the possibility of infection since occlusion dressing provides a warm and moist environment for bacterial multiplication.^11–15
Many methodologies have been used to evaluate the wound healing process and the effects of wound dressings.^16–18 In natural settings, however, clinical wounds have various etiologies: patients’physiologic conditions, systemic medications, wound sizes, and depth. The present study focuses on experimental wound studies, sine qua non before dealing with the more complex clinical wound.

Occlusion

Occlusion refers to skin covered directly or indirectly by impermeable films or devices such as diapers, tape, chambers, gloves, textiles garments, wound dressings, and transdermal devices.¹⁹ In addition, certain topical vehicles that contain fats and/or polymer oils (eg, petrolatum and paraffin) may also generate occlusive effects.¹⁴ Occlusion frequently, but not universally, increases percutaneous absorption to applied chemicals.^20–22 The effects of occlusion on skin are complex and may produce profound changes that include altering epidermal lipids, DNA synthesis, epidermal turnover, pH, epidermal morphology, sweat glands, and Langerhans cells stresses.^14,19–29 Evaluation and investigation of the impact of occlusion on barrier function are important in many fields such as, skin physiology, pathology, pharmacology, and dermatology. Recent reviews provide detailed information pertaining to occlusion on barrier function.^{14,20,24,25,29–32}

History of Wound Dressings

The first recorded use of an occlusive wound dressing is 1615 BC.¹ It was more common for wound management clinicians to leave the wounds open until Winter,² on the basis of a pig model, advocated the concept of moist wound healing in 1962. Hinman and Maibach,³ in a human experiment, showed that an occlusive dressing accelerates healing. These studies resulted in commercialization of occlusive wound dressings that led many professionals to study in this area in an attempt to develop better dressings.
Classifications. The most common classification of wound dressings is based on their components, films, foams, gels, hydrogels, hydrocolloids, alginates, cellophane, and specialty. Details are described previously.^1,7 Since this review focuses on occlusive dressings,wound dressings were simplified into 2 types, regardless of their material components (ie, fully occlusive [or called occlusive] and semi-occlusive). The occlusive dressing is defined as impermeable to water vapor, and semi-occlusive is defined as moisture vapor permeable.⁵
Advantages and disadvantages. Advantages of occlusive dressings include reducing wound surface necrosis, preventing wound desiccation, decreasing wound pain, increasing wound healing rates, decreasing wound care, stimulating growth factors, activating enzymes needed for debridement, and providing protection for wounds.^1,6,7 A major disadvantage is concern for infection.¹ Hinman and Maibach,³ in the first controlled human study on occlusive dressings, raised a concern about possible infection; time and experience suggest that this is uncommon.

Dressings on experimental wounds. Since wounds in a typical clinical setting are often not comparable because of a variety of uncontrolled factors, data from the literature were condensed and only include experimental controlled wound healing studies (see Tables 1–4).
The results of occlusive dressings on animal wound models are in Table 1. Positive and negative effects on wound healing are almost equal. It is important to note that all negative reports utilized latex as the impermeable membrane.
Table 2 shows that all but 1 semi-occlusive dressing improved wound healing. In human wound models, occlusive dressings have variable effects (Table 3), but semi-occlusive dressings only demonstrated benefits (Table 4).

Discussion

There are an abundance of experimental data published on the effects of “moist wound healing” under occlusive or semi-occlusive dressings. There is even more published information on the clinical use of these types of dressings. Undoubtedly there is a role for dressings that maintain hydration of wound tissues, and therefore, viability.
Clinical wound healing is a complex biological process and may boe affected by multiple factors including endogenous (etiologic, physiologic conditions) and exogenous (environmental,systemic medication).^47–50 The opinions or discrepancies in the use of wound dressings may be explained due to those factors in the models employed. For example, acetone treatment as a chemical produced wound model that deletes lipids from stratum corneum may differ from full-thickness wounds that induced by the physical mechanism. This might help explain the controversial conclusions in Table 1. Levy et al⁹ utilized aluminum chamber or foils as the occlusive material (Table 3). These materials might interact with suction blister skin wounds and might lead to a negative result. The Visscher et al¹⁰ data can not be explained, and one can only speculate that cellophane tape stripping layers may be of a significantly different biology than the original split-thickness wound utilized by Winter² and Hinman and Maibach.³ All reports demonstrate the favorable effects of semi-occlusive materials (Table 4). However, Welzel et al⁴⁶ concluded semipermeable mem-branes had no effect on wound healing, and that the number of tape layer stripping could be a factor. For example, the partial removal of the stratum corneum could differ to full removal of stratum corneum and epidermis. While the regeneration of stratum corneum is an important last phase of most wound healing, one should not focus on “forced regeneration” following tape stripping as being relevant to most of the challenges of dealing with partial- or full-thickness wounds.
Occlusive dressings may sometimes delay wound healing. Evidence from studies on tape stripped wounds, and the ensuing forced regeneration and maturation of stratum corneum, seems to support this statement.^8,10,41,42 As previously stated, occlusive dressings facilitate epidermal wound healing (positive effects on epithelial migration, reduction of inflammation, minimizing eschar anddehydration necrosis, and enhancing wound closure).
Individual differences in animal and human wound models may determine species specific responses and discriminate the effects of imposed variables on specific aspects of healing.^51,52 The species and wound differences are important. Loose-skinned animals, (eg, rabbits and mice) seem to respond differently from other animals from which data are available; closure of full-thickness excisions in mice seem to be delayed by occlusion (personal observation); this may also be true for rabbits. The negative results widely reported with the use of latex films are interesting and should be explored further.^8,15,38–43 In dressing evaluation, this type of experimental procedure is essential. Material such as latex, which is used in several studies,^8,15,38–43 may be irritating and may alter healing. This may be applicable to some of the negative outcomes (Table 1). In some instances, results from nude mice may be misleading. A nude mouse has a very thin epidermis and the tape stripping can be variable, as is the thickness of the epidermis, in relation to the age and sex of the mouse.The blistering technique is very difficult in mice and may not be reproducible because the skin of a nude mouse has utricles and cysts within the dermis. It is difficult to translate these data into actual clinical outcomes in humans.
The biologic effects of dressings remain a complex science—at a minimum, clinical relevance to humans requires a multifaceted interpretation based on our current knowledge of “validation for man.” When can we extrapolate from rodents to humans? What is the overlying “Rosetta Stone” that might relate the more “superficial” wound healing (stripping and/or solvent extraction) knowledge to split- and full-thickness wounds? What can be learned from other factors (O₂, CO₂, and electrolyte transport)? These represent but a few of the challenges for wound dressing developers.
There was concern that the moist environment created under occlusion would increase wound infection rates through the proliferation of pathogenic microorganisms.³ However, controlled studies have revealed thatbacterial colonization under occlusion does not frequently impair wound healing clinically, and infection rates with occlusion are frequently less than those with non-occlusive dressings.⁵³ However, one still must exercise common sense and clinical judgment in preparing the wound bed for any subsequent treatment.
Occlusion presents a new set of challenges for intact skin: occlusive dressings will allow for the growth of large bacterial populations on the skin surface. Eccrine ducts will become blocked.⁵⁴ Other changes may also occur. These cutaneous effects and challenges led to the adoption of plastic films, which have varying degrees of moisture vapor permeability (notably, the polyurethane films). Over intact skin, they can maintain an environment, which is acceptable. In the presence of exudate (liquid), these films act much like the impermeable Saran^™ films used in many experimental studies. Another consideration in the development of these permeable dressings may be the moisture vapor permeability characteristics of the adhesive used.
Due to the multietiologic nature of wounds, it is not likely that a single dressing will suffice for all wounds. Wound dressing development with different types of materials and functions to treat the wound should be evaluated on a case by case basis.
The ideal synthetic wound dressing may be the semiocclusive. It should absorb exudate (thus decreasing bacteria), permit fluid evaporation, and should not be incorporated into the eschar or should be sufficiently fragile to facilitate removal without compromising the healing wound. While some of these attributes are certainly important, other approaches have been the inclusion of antibacterial agents (notably, silver-containing dressings) to maintain bacterial populations at levels handled by the host’s immune responses.
Advanced dressings attempt to specifically maintain a moist wound environment. Natural, pure, and nonwoven dressings may rapidly absorb and retain wound fluid to form an integral gelled structure, thereby maintaining an ideal moist wound healing environment.^7,55 It can also trap and immobilize pathogenic bacteria in the network of gelled fibers, stimulate macrophage activity, and activate platelets resulting in hemostasis and accelerated wound healing.
Wound dressings remain a standard treatment since the overall advantages and effectiveness outweigh the disadvantages. Semi-occlusive dressings may provide superior outcomes. Some have argued that occlusive dressings may suppress barrier recovery and reduce the epidermal proliferative response to an abnormal stratum corneum barrier^8,46—Rovee et al⁵⁶ presented in-depth insights on these points. Earlier, Fisher and Maibach⁵⁷ pointed out the importance of an air interface for the final maturation of the stratum corneum following tape stripping; this is also well known by those who have studied the formation of epidermis in organotypic cell culture systems.
The intention is to not over-generalize this conclusion in the hope that other important studies have not been overlooked. Taken together, early observations of the properties of occlusion in wound healing by Winter² and Hinman and Maibach³ are not abrogated; yet, the challenges summarized above mandate detailed clarifications because of the frequency of wounds requiring management.
Today, with the rapid development of new technologies and materials in bioscience, one can expect greater efficacy and optimal dressings or materials, and perhaps more refined technology to metric efficacy and explore mechanisms.

Acknowledgment

The authors thank Dr. David Rovee, PhD for kindly providing expert advice.