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Temporary Angiogenic Transformation of the Skin Graft Vasculature after Reperfusion

Lindenblatt, Nicole M.D.; Platz, Uwe; Althaus, Martina; Hegland, Niels; Schmidt, Christian A. M.D., Ph.D.; Contaldo, Claudio M.D.; Vollmar, Brigitte M.D.; Giovanoli, Pietro M.D.; Calcagni, Maurizio M.D.

Plastic and Reconstructive Surgery: July 2010 - Volume 126 - Issue 1 - p 61-70
doi: 10.1097/PRS.0b013e3181da87f6
Experimental: Original Articles

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.

Zürich, Switzerland; and Rostock, Germany

From the Division of Plastic and Reconstructive Surgery and the Division of Cardiovascular Surgery, Department of Surgery, University Hospital Zurich, and the Institute for Experimental Surgery, University of Rostock.

Received for publication October 20, 2009; accepted December 10, 2009.

Presented in part at the European Congress of Scientists and Plastic Surgeons, in Bern, Switzerland, September 12 through 13, 2008, and at the European Plastic Surgery Research Council, in Hamburg, Germany, August of 2009.

Disclosure: This study was supported financially by the Hartmann-Muller-Foundation, Zurich, Switzerland, and the FORUN Program of the University of Rostock, Rostock, Germany. The authors declare that they have no competing financial interests, commercial associations, or financial disclosures that might pose or create a conflict of interest with information presented in the article.

Nicole Lindenblatt, M.D., Division of Plastic and Reconstructive Surgery, University Hospital Zurich, Ramistraße 100, 8091 Zurich, Switzerland,

©2010American Society of Plastic Surgeons