Topical vanadate improves tensile strength and alters collagen organisation of excisional wounds in a mouse model |
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Authors: | Hendrik Lintel BS Darren B. Abbas MD Duncan J. Mackay MD MBA Michelle Griffin MBChB PhD Christopher V. Lavin MD Charlotte E. Berry BS Nicholas J. Guardino BS Jason L. Guo PhD Arash Momeni MD Donald R. Mackay MD DDS Michael T. Longaker MD MBA Derrick C. Wan MD |
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Affiliation: | 1. Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA;2. Department of Plastic Surgery, Pennsylvania State University Hershey Medical Center, Hershey, Pennsylvania, USA;3. Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, California, USA |
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Abstract: | Wound dehiscence, oftentimes a result of the poor tensile strength of early healing wounds, is a significant threat to the post-operative patient, potentially causing life-threatening complications. Vanadate, a protein tyrosine phosphatase inhibitor, has been shown to alter the organisation of deposited collagen in healing wounds and significantly improve the tensile strength of incisional wounds in rats. In this study, we sought to explore the effects of locally administered vanadate on tensile strength and collagen organisation in both the early and remodelling phases of excisional wound healing in a murine model. Wild-type mice underwent stented excisional wounding on their dorsal skin and were divided equally into three treatment conditions: vanadate injection, saline injection control and an untreated control. Tensile strength testing, in vivo suction Cutometer analysis, gross wound measurements and histologic analysis were performed during healing, immediately upon wound closure, and after 4 weeks of remodelling. We found that vanadate treatment significantly increased the tensile strength of wounds and their stiffness relative to control wounds, both immediately upon healing and into the remodelling phase. Histologic analysis revealed that these biomechanical changes were likely the result of increased collagen deposition and an altered collagen organisation composed of thicker and distinctly organised collagen bundles. Given the risk that dehiscence poses to all operative patients, vanadate presents an interesting therapeutic avenue to improve the strength of post-operative wounds and unstable chronic wounds to reduce the risk of dehiscence. |
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Keywords: | collagen tensile strength vanadate wound healing |
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