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Analysis of Nerve and Neuropeptide Patterns in Vacuum-Assisted Closure–Treated Diabetic Murine Wounds

Younan, George M.D.; Ogawa, Rei M.D., Ph.D.; Ramirez, Michelle B.A.; Helm, Douglas M.D.; Dastouri, Pouya M.D.; Orgill, Dennis P. M.D., Ph.D.

Plastic and Reconstructive Surgery: July 2010 - Volume 126 - Issue 1 - p 87-96
doi: 10.1097/PRS.0b013e3181da86d0
Experimental: Original Articles

Background: Reestablishment of the peripheral nervous system occurs in parallel with wound healing. With accelerated wound healing seen with the vacuum-assisted closure device, the authors studied its effects on nerve fiber regeneration, nerve sprouting, and the stimulation of neuropeptides and neurotrophins.

Methods: A vacuum-assisted closure device was applied to a full-thickness diabetic mouse wound using continuous or cyclical modes and compared with foam dressing or occlusive dressing controls, using 10 mice per group. Nerve fibers, substance P, calcitonin gene-related peptide, and nerve growth factor were analyzed using two-dimensional immunohistochemistry and real-time reverse-transcriptase polymerase chain reaction.

Results: A significant increase in dermal and epidermal nerve fiber densities and in substance P, calcitonin gene-related peptide, and nerve growth factor expression was seen in vacuum-assisted closure–treated wounds. Cyclical treatment mode correlated with the largest increase in granulation tissue production, wound surface microdeformations, and a slightly faster wound closure rate.

Conclusions: This study suggests that vacuum-assisted closure therapy can modulate nerve fiber and neuropeptide production in the wound. Optimized kinetics of vacuum-assisted closure application may provide an opportunity for clinicians to further improve wound healing in denervated wounds such as pressure sores and diabetic foot ulcerations.

Boston, Mass.; and Tokyo, Japan

From the Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, and the Department of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School.

Received for publication July 30, 2009; accepted January 6, 2010.

Disclosures: Dr. Orgill is the principal investigator on studies receiving research grants to the Brigham and Women's Hospital by Kinetic Concepts, Inc., San Antonio, Texas, and is also an expert witness for Kinetic Concepts, Inc. The bioreactor used in this study, suction apparatus, and foam were provided by Kinetic Concepts, Inc. The other authors have no financial conflicts of interest and do not have any financial or business liaison to Kinetic Concepts, Inc.

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

©2010American Society of Plastic Surgeons