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VEGF Improves Skeletal Muscle Regeneration After Acute Trauma and Reconstruction of the Limb in a Rabbit Model

  • Basic Research
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Complicated tibial fractures with severe soft tissue trauma are challenging to treat. Frequently associated acute compartment syndrome can result in scarring of muscles with impaired function. Several studies have shown a relationship between angiogenesis and more effective muscle regeneration. Vascular endothelial growth factor (VEGF) is associated with angiogenesis but it is not clear whether it would restore muscle force, reduce scarring, and aid in muscle regeneration after acute musculoskeletal trauma.

Questions/purposes

Therefore, we asked whether local application of VEGF (1) restores muscle force, (2) reduces scar tissue formation, and (3) regenerates muscle tissue.

Methods

We generated acute soft tissue trauma with increased compartment pressure in 22 rabbits and shortened the limbs to simulate fracture débridement. In the test group (n = 11), a VEGF-coated collagen matrix was applied locally around the osteotomy site. After 10 days of limb shortening, gradual distraction of 0.5 mm per 12 hours was performed to restore the original length. Muscle force was measured before trauma and on every fifth day after trauma. Forty days after shortening we euthanized the animals and histologically determined the percentage of connective and muscle tissue.

Results

Recovery of preinjury muscle strength was greater in the VEGF group (2.4 N; 73%) when compared with the control (1.8 N; 53%) with less connective and more muscle tissue in the VEGF group. The recovery of force was related to the percentage of connective tissue versus muscle fibers.

Conclusions

Local application of VEGF may improve restoration of muscle force by reducing connective tissue and increasing the relative amount of muscle fibers.

Clinical Relevance

VEGF may be useful to improve skeletal muscle repair by modulating muscle tissue regeneration and fibrosis reduction after acute trauma.

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Acknowledgments

We thank Karim Gorschlueter MD, former medical student at the University of Muenster, for assistance with the muscle force measurements and histologic and histomorphometric analyses, Torsten Blunk PhD for his support discussing the results, James Ridgley MD for critically reviewing the manuscript as a native speaker, and Daniela Keller Dipl. Math.-statistics for her excellent support.

Author information

Authors and Affiliations

  1. Department of Trauma, Hand, Plastic and Reconstructive Surgery, University of Wuerzburg, Oberduerrbacher Str 6, 97080, Wuerzburg, Germany

    Soenke Percy Frey MD, Hendrik Jansen MD & Rainer H. Meffert MD

  2. Department of Trauma, Hand and Reconstructive Surgery, University of Muenster, Muenster, Germany

    Michael J. Raschke MD & Sabine Ochman MD

Authors
  1. Soenke Percy Frey MD
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  2. Hendrik Jansen MD
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  3. Michael J. Raschke MD
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  4. Rainer H. Meffert MD
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  5. Sabine Ochman MD
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Corresponding author

Correspondence to Soenke Percy Frey MD.

Additional information

One of the authors certifies that he (SPF) has or may receive payments or benefits, during the study period, an amount less than $10,000, from IZKF Wuerzburg (Interdisziplinäres Zentrum für Klinische Forschung), University of Wuerzburg, Wuerzburg, Germany.

One of the authors (SO) has or may receive payments or benefits, during the study period, an amount less than $10,000, from IMF (Innovative Medizinische Forschung), University of Muenster, Muenster, Germany.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.

Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at the University of Wuerzburg, Wuerzburg, Germany, and the University of Muenster, Muenster, Germany, in equal parts.

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Frey, S.P., Jansen, H., Raschke, M.J. et al. VEGF Improves Skeletal Muscle Regeneration After Acute Trauma and Reconstruction of the Limb in a Rabbit Model. Clin Orthop Relat Res 470, 3607–3614 (2012). https://doi.org/10.1007/s11999-012-2456-7

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  • DOI: https://doi.org/10.1007/s11999-012-2456-7

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