Temporary angiogenic transformation of the skin graft vasculature after reperfusion

Abstract

Background: In the era of tissue engineering, the physiologic process of skin graft revascularization remains unclear, preventing the successful development of skin substitutes. Therefore, the authors developed a new in vivo model with which to visualize the process of engraftment and its microvascular architecture. The aim of this study was to specifically investigate the vascular transformations within the skin graft to gain applicable knowledge on how vascular processes during engraftment occur.

Methods: Microsurgical preparation of the modified dorsal skinfold chamber including autologous skin grafting was performed in male C57BL/6J mice (n = 10). In addition, immunohistochemistry of angiogenic factors, endothelial cells, and pericytes, and corrosion casting were performed to further characterize the specific mechanisms.

Results: The graft exhibited capillary widening starting at day 3, resulting in the temporary formation of spherical protrusions at the graft capillary divisions starting in the center of the graft 24 to 48 hours after revascularization. Confocal microscopy showed the simultaneous expression of CD31 and desmin. Corrosion casting and evaluation by light microscopy and scanning electron microscopy showed the three-dimensional formation of capillaries in the wound bed that connected to the preexisting capillary loops of the skin graft.

Conclusions: The authors were able to show for the first time a temporary angiogenic response within the capillaries of the skin graft. This most likely represents a reaction to reperfusion allowing the supply of proangiogenic factors to the hypoxic skin graft. The detection of an angiogenic response within the graft capillaries is for the first time made possible in the newly developed model and is therefore completely novel.