Abstract

Models of skin graft revascularization are mostly based on histological evaluations, but lack the possibility to analyze the vascular biology in vivo. The aim of the present study was therefore to develop an animal model which allows continuous monitoring of the microcirculation during skin graft healing. Skin and subcutaneous tissue were removed from the back of dorsal skinfold chamber preparations in mice, leaving one layer of striated muscle and subcutaneous tissue as wound bed. A respective full-thickness skin graft was harvested from the groin and sutured into the defect in the back of the chamber. To study graft healing, repetitive intravital microscopy was performed during the first 10 days after engraftment. Capillary widening in the wound bed appeared at day 1 after grafting and increased until day 4. Capillary buds and sprouts firstly appeared at day 2. Blood filling of autochthonous graft capillaries occurred at day 3, resulting in almost complete restoration of the original skin microcirculation at day 5. This was achieved by interconnections between the microvasculature of the wound bed and the skin graft through a temporary angiogenic response. In principle, angiogenic blood vessel growth originated in the wound bed and was directed towards the graft. This new model allows for repetitive analysis of the microcirculation during skin graft healing. It provides ideal in vivo conditions to further delineate the exact mechanisms of blood vessel interconnection during the complex process of angiogenesis, and may also allow to study the vascularization of tissueengineered skin substitutes.

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