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The growth hormone is involved in skin homeostasis and wound healing. We hypothesize whether it is possible to improve pressure ulcer (PU) healing by locally applying the recombinant human growth hormone (rhGH) in a human skin mouse model. Non-obese diabetic/severe combined immunodeficient mice ( n = 10) were engrafted with a full-thickness human skin graft. After 60 days with stable grafts, human skin underwent three cycles of ischemia-reperfusion with a compression device to create a PU. Mice were classified into two groups: rhGH treatment group ( n = 5) and control group ( n = 5). In the rhGH group for local intradermal injections, each had 0.15 mg (0.5IU) applied to the PU edges, once per week for four weeks. Evaluation of the wound healing was conducted with photographic and visual assessments, and histological analysis was performed after complete wound healing. The results showed a healing rate twice as fast in the rhGH group compared to the control group (1.25 ± 0.33 mm2/day versus 0.61 ± 0.27 mm2/day; p -value < 0.05), with a faster healing rate during the first 30 days. The rhGH group showed thicker skin (1953 ± 457 µm versus 1060 ± 208 µm; p -value < 0.05) in the repaired area, with a significant decrease in collagen type I/III ratio at wound closure (62 days, range 60-70). Local administration of the rhGH accelerates PU healing in our model. The rhGH may have a clinical use in pressure ulcer treatment.

Despite advances in regenerative medicine and tissue engineering, human skin substitutes remain a clear goal to achieve. Autografts remain the principal clinical option. The long-term changes in dermis, as well as its response after injuries, are not well known. Research in this field has been hindered by a lack of experimental animal models. This study analyzes the architectural dermal scaffold (collagen and elastin fibers plus fibrillin-microfibrils) changes in a model of human skin pressure ulcers in mice. Immunosuppressed NOD/Scid mice (n=10) were engrafted with human skin of dimensions 4x3 cm. After 60 days as a permanent graft, a pressure ulcer (PU) was created in the human skin using a compression device. Three study groups were established: full-thickness skin graft before (hFTSG) and after applying mechanical pressure (hFTSG-PU). Native human skin was used as control group. Evaluations were conducted with visual and histological assessment. Scaffold components from each group were compared by immunohistochemical staining (tropoelastin, collagen I and III, metalloproteins (MMP), fibulins, and lysil oxidases (LOX) among others). The long-term engrafted skin showed a certain degradative state of dermis scaffold, as noticed by the active expression of MMPs and tropoelastin compared to native skin. However, a great reparative response after pressure ulcer onto the engrafted skin was observed. A significant increase of fibrillin microfibrils components (TGF-β, MAGP-1 and fibrillin-1), and matrix suprastructures of collagen I, III and LOX lead to an active restructuration of dermal tissue. Our human skin model in mice revealed the important role of the dermal scaffold component to reach skin stability and its capability to react to mechanical pressure injuries. These results showed the important role of dermal scaffold to support the histoarchitecture and mechanosensation of the human skin.

Introduction: Pressure ulcers are a prevalent health problem in today's society. The shortage of suitable animal models limits our understanding and our ability to develop new therapies. This study aims to report on the development of a novel and reproducible human skin pressure ulcer model in mice., Material and Methods: Male non-obese, diabetic, severe combined immunodeficiency mice (n = 22) were engrafted with human skin. A full-thickness skin graft was placed onto 4×3 cm wounds created on the dorsal skin of the mice. Two groups with permanent grafts were studied after 60 days. The control group (n = 6) was focused on the process of engraftment. Evaluations were conducted with photographic assessment, histological analysis and fluorescence in situ hybridization (FISH) techniques. The pressure ulcer group (n = 12) was created using a compression device. A pressure of 150 mmHg for 8 h, with a total of three cycles of compression-release was exerted. Evaluations were conducted with photographic assessment and histological analysis., Results: Skin grafts in the control group took successfully, as shown by visual assessment, FISH techniques and histological analysis. Pressure ulcers in the second group showed full-thickness skin loss with damage and necrosis of all the epidermal and dermal layers (ulcer stage III) in all cases. Complete repair occurred after 40 days., Conclusions: An inexpensive, reproducible human skin pressure ulcer model has been developed. This novel model will facilitate the development of new clinically relevant therapeutic strategies that can be tested directly on human skin.