A new model for studying the revascularization of skin grafts in vivo: the role of angiogenesis.
BACKGROUND
Models of skin graft revascularization are based mostly on histologic evaluations but lack the possibility of analyzing the vascular biology in vivo. The aim of the present study was therefore to develop an animal model that allows continuous monitoring of the microcirculation during skin graft healing.


METHODS
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 a wound bed (n = 5). A corresponding 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.


RESULTS
Capillary widening in the wound bed appeared at day 1 after grafting and increased until day 4. Capillary buds and sprouts first appeared at day 2. Blood filling of autochthonous graft capillaries occurred at day 3, resulting in almost complete restoration of the original skin microcirculation on 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 toward the graft.


CONCLUSIONS
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 study of the vascularization of tissue-engineered skin substitutes.
Lindenblatt
Nicole
N
Zurich, Switzerland; and Homburg-Saar and Rostock, Germany From the Division of Plastic and Reconstructive Surgery, University Hospital Zurich; the Institute for Clinical and Experimental Surgery, University of Saarland; and the Institute for Experimental Surgery, University of Rostock.
Calcagni
Maurizio
M
Contaldo
Claudio
C
Menger
Michael D
MD
Giovanoli
Pietro
P
Vollmar
Brigitte
B
D000818:Animals; D031176:Bidens / Q000378:metabolism; D002196:Capillaries / Q000502:physiology; D003872:Dermatitis / Q000503:physiopathology; D062109:Dermatologic Surgical Procedures; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology; D008853:Microscopy / Q000295:instrumentation* / Q000379:methods; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012867:Skin / Q000098:blood supply* / Q000378:metabolism; D016038:Skin Transplantation; D013997:Time Factors; D020858:Tissue and Organ Harvesting; D014743:Videotape Recording; D014945:Wound Healing / Q000502:physiology
C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019408:Platelet Endothelial Cell Adhesion Molecule-1