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Angiogenesis

, 11:369 | Cite as

Angiogenic response to extracorporeal shock wave treatment in murine skin isografts

  • Alexander Stojadinovic
  • Eric A. Elster
  • Khairul Anam
  • Douglas Tadaki
  • Mihret Amare
  • Stephen Zins
  • Thomas A. DavisEmail author
Original Paper

Abstract

Skin grafts are commonly utilized and proven effective methods of open wound coverage. Revascularization through neoangiogenesis is a pivotal mechanism for skin graft integration and durability. Extracorporeal shock-wave treatment (ESWT) has been demonstrated to accelerate wound repair; however, its mechanism-of-action is unclear. We investigated the role of ESWT in early revascularization of full-thickness skin isografts in a murine model. Cohorts of mice were euthanized and skin grafts were harvested 6 h, 2, 4, and 7 days post grafting ± ESWT. Various aspects of graft neovascularization were measured including gross morphology, quantitative microscopy (vessel number, density), immunohistochemistry (CD31), cDNA SuperArrays for 84 angiogenesis-specific genes, and custom-designed ‘Wound Repair’ TaqMan® Low Density Array (TLDA) cards to assess expression of 188 wound repair genes. We demonstrate that a single administration of ESWT immediately following skin grafting significantly enhances recipient graft revascularization (increased vessel number, size, and density). An augmented early pro-angiogenic and suppressed delayed pro-inflammatory response to ESWT was accompanied by significantly increased expression of both skin graft CD31 and angiogenesis pathway-specific genes, including ELR-CXC chemokines (CXCL1, CXCL2, CXCL5), CC chemokines (CCL2, CCL3, CCL4), cytokines (IL-1β, IL-6, G-CSF, VEGF-A), matrix metalloproteinases (MMP3, MMP9, MMP13), hypoxia-inducible factors (HIF-1α), and vascular remodeling kinase (Mst1), as early as 6 h and up to 7 days post grafting and treatment. These findings suggest that early pro-angiogenic and anti-inflammatory effects of ESWT promote tissue revascularization and wound healing by augmenting angiogenesis and dampening inflammation.

Keywords

Angiogenesis Extracorporeal shock wave therapy Skin graft Wound healing 

Abbreviations

ESWT

Extracorporeal shock wave treatment

Notes

Acknowledgments

This work was supported by ONR work unit 602236N.42237.W160.A0806 and by the Combat Wound Initiative Program, a Congressionally funded program of the Henry M. Jackson Foundation for the Advancement of Military Medicine.

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Alexander Stojadinovic
    • 1
    • 2
  • Eric A. Elster
    • 2
    • 3
    • 4
  • Khairul Anam
    • 3
  • Douglas Tadaki
    • 2
    • 3
  • Mihret Amare
    • 3
  • Stephen Zins
    • 3
  • Thomas A. Davis
    • 1
    • 3
    Email author
  1. 1.Combat Wound Initiative Program, Department of SurgeryWalter Reed Army Medical CenterWashingtonUSA
  2. 2.Department of SurgeryUniformed Services University of the Health SciencesBethesdaUSA
  3. 3.Regenerative Medicine Department, Combat Casualty CareNaval Medical Research CenterSilver SpringUSA
  4. 4.Combat Wound Initiative Program, Department of SurgeryNational Naval Medical CenterBethesdaUSA

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