Hyperbaric oxygen stimulates epidermal reconstruction in human skin equivalents

Abstract

The crucial role of oxygen during the complex process of wound healing has been extensively described. In chronic or nonhealing wounds, much evidence has been reported indicating that a lack of oxygen is a major contributing factor. Although still controversial, the therapeutic application of hyperbaric oxygen (HBO) therapy can aid the healing of chronic wounds. However, how HBO affects reepithelization, involving processes such as keratinocyte proliferation and differentiation, remains unclear. We therefore used a three-dimensional human skin-equivalent (HSE) model to investigate the effects of daily 90-minute HBO treatments on the reconstruction of an epidermis. Epidermal markers of proliferation, differentiation, and basement membrane components associated with a developing epidermis, including p63, collagen type IV, and cytokeratins 6, 10, and 14, were evaluated. Morphometric analysis of hematoxylin and eosin-stained cross sections revealed that HBO treatments significantly accelerated cornification of the stratum corneum compared with controls. Protein expression as determined by immunohistochemical analysis confirmed the accelerated epidermal maturation. In addition, early keratinocyte migration was enhanced by HBO. Thus, HBO treatments stimulate epidermal reconstruction in an HSE. These results further support the importance of oxygen during the process of wound healing and the potential role of HBO therapy in cutaneous wound healing.

Characterization of a Human Skin Equivalent Model to Study the Effects of Ultraviolet B Radiation on Keratinocytes

“…These HSEs may then be cultured at the air-liquid interface in order to promote keratinocyte differentiation and epidermogenesis. [20][21][22] This results in the formation of an epidermal layer that is histologically similar to native human skin. 21 These tissue-engineered constructs serve as versatile and powerful research tools with numerous applications, such as the study of cancer, pigmentation, and toxicity.…”

“…20,21 Here, we describe an additional application of the HSE-DED to characterize the epidermal UVB photoresponse in vitro. Specifically, the HSE-DED was validated in terms of (1) the expression of key epidermal differentiation markers compared with native skin; (2) the generation of characteristic markers of UVB photodamage; and (3) the capacity for postirradiation repair and regeneration at cellular and epidermal tissue levels.…”

Mild hyperbaric oxygen activates the proliferation of epidermal basal cells in aged mice

“…Another study using keratinocyte cultures found that the epidermis needs to sustain higher oxygen levels than many internal tissues and that human epidermal cultures incubated in 21% oxygen attained a greater thickness than those incubated in 2% oxygen. Moreover, wounds covered with oxygen‐impermeable plastic films took longer to heal than those exposed to normal oxygen concentrations . These findings suggest that an adequate supply of oxygen accelerates the proliferation of epidermal basal cells.…”

Wound bed preparation and oxygen balance – a new component?

“… Energy metabolism – oxygen is the last electron acceptor for mitochondrial cytochrome oxidase leading to the production of high‐energy phosphates that are required for multiple cellular functions (42,43). Collagen synthesis – oxygen is involved in the hydroxylation of proline and lysine in procollagen that is crucial in collagen maturation (44,45). Neovascularisation – although relative hypoxia is required to engender neovascularisation, supplemental oxygen administration has been shown to sustain and accelerate vessel growth. Oxygen induces vascular endothelial growth factor mRNA levels in endothelial cells and macrophages in vivo (41,46,47).…”