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External Volume Expansion Increases Subcutaneous Thickness, Cell Proliferation, and Vascular Remodeling in a Murine Model

Heit, Yvonne I. M.D.; Lancerotto, Luca M.D.; Mesteri, Ildiko M.D.; Ackermann, Maximilian M.D.; Navarrete, Maria F. M.D.; Nguyen, Collin T. M.Sc.; Mukundan, Srinivasan Jr. M.D., Ph.D.; Konerding, Moritz A. M.D.; Del Vecchio, Daniel A. M.D.; Orgill, Dennis P. M.D., Ph.D.

Plastic and Reconstructive Surgery: September 2012 - Volume 130 - Issue 3 - p 541–547
doi: 10.1097/PRS.0b013e31825dc04d
Experimental: Original Articles

Background: Fat grafting is a powerful tool for soft-tissue reconstruction; however, the science behind recipient bed preparation has not been thoroughly explored. External volume expansion using suction before fat grafting has been used clinically to improve reliability and consistency of graft survival. The authors developed a murine model to investigate the underlying mechanism of external volume expansion.

Methods: The authors created an external volume expansion device using a soft-silicone dome connected to a vacuum source (25 mmHg) to treat the dorsum of mice, and the response was compared with treatment with an occlusive dressing. Treated areas were monitored with magnetic resonance imaging. Remodeling of microvasculature was studied with corrosion casting on day 7. Effects on tissue thickness, number of adipocytes, cell proliferation, and blood vessel density were analyzed at 28 days.

Results: Macroscopic analysis showed tissue swelling at sites treated with the external volume expansion device by 21 days, without skin damage. On day 28, external volume expansion increased the thickness of the subcutaneous fat layer twofold, consistent with magnetic resonance imaging observations. The proliferation rate in the subcutaneous layer of expansion-treated areas increased twofold, with a net 2.2-fold increase in number of adipocytes in columns; remodeling of the vessels network occurred, with reorientation and increase of vessel diameters shown by corrosion casting and 1.9-fold augmentation of vessels density.

Conclusions: External volume expansion applied to mouse integument induces highly proliferative and vascularized subcutaneous tissue. Recipient-site preparation using external volume expansion devices may be a promising tool to enhance cell and tissue engraftment.

Boston, Mass.; Magdeburg, Germany; Padova, Italy; Vienna, Austria; Mainz, Germany; and Santiago, Chile

From the Tissue Engineering and Wound Healing Laboratory, Division of Plastic Surgery, and Department of Radiology, Brigham and Women's Hospital and Harvard Medical School; Department of Plastic, Aesthetic, and Hand Surgery, Otto-von-Guericke University of Magdeburg; Institute of Plastic Surgery, University of Padova; Clinical Institute of Pathology, University of Vienna; Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz; Department of Surgery, Pontificia Universidad Católica de Chile; and Back Bay Plastic Surgery and Massachusetts General Hospital—Harvard Medical School.

Received for publication January 27, 2012; accepted March 13, 2012.

The first two authors contributed equally to the work.

Presented at the International Conference on Adipose Tissue, in Venice, Italy, December 1 through 3, 2011.

Disclosure: None of the authors has any commercial or financial interests to disclose. This study did not receive any external financial support.

Dennis P. Orgill, M.D., Ph.D.; Division of Plastic Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, Mass. 02115,

©2012American Society of Plastic Surgeons