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Characterization of a composite injury model of severe lower limb bone and nerve trauma.

Publication ,  Journal Article
Uhrig, BA; Clements, IP; Boerckel, JD; Huebsch, N; Bellamkonda, RV; Guldberg, RE
Published in: Journal of tissue engineering and regenerative medicine
June 2014

Severe extremity trauma often results in large zones of injury comprising multiple types of tissue and presents many clinical challenges for reconstruction. Considerable investigation is ongoing in tissue engineering and regenerative medicine therapeutics to improve reconstruction outcomes; however, the vast majority of musculoskeletal trauma models employed for testing the therapeutics consist of single-tissue defects, offering limited utility for investigating strategies for multi-tissue repair. Here we present the first model of composite lower limb bone and nerve injury, characterized by comparison to well-established, single-tissue injury models, using biomaterials-based technologies previously demonstrated to show promise in those models. Quantitative functional outcome measures were incorporated to facilitate assessment of new technologies to promote structural and functional limb salvage following severe extremity trauma. Nerve injury induced significant changes in the morphology and mechanical properties of intact bones. However, BMP-mediated segmental bone regeneration was not significantly impaired by concomitant nerve injury, as evaluated via radiographs, microcomputed tomography (μCT) and biomechanical testing. Neither was nerve regeneration significantly impaired by bone injury when evaluated via histology and electrophysiology. Despite the similar tissue regeneration observed, the composite injury group experienced a marked functional deficit in the operated limb compared to either of the single-tissue injury groups, as determined by quantitative, automated CatWalk gait analysis. As a whole, this study presents a challenging, clinically relevant model of severe extremity trauma to bone and nerve tissue, and emphasizes the need to incorporate quantitative functional outcome measures to benchmark tissue engineering therapies.

Duke Scholars

Published In

Journal of tissue engineering and regenerative medicine

DOI

EISSN

1932-7005

ISSN

1932-6254

Publication Date

June 2014

Volume

8

Issue

6

Start / End Page

432 / 441

Related Subject Headings

  • X-Ray Microtomography
  • Trauma, Nervous System
  • Rats, Inbred Lew
  • Nerve Regeneration
  • Lower Extremity
  • In Vitro Techniques
  • Gait
  • Female
  • Electrophysiological Phenomena
  • Disease Models, Animal
 

Citation

APA
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MLA
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Uhrig, B. A., Clements, I. P., Boerckel, J. D., Huebsch, N., Bellamkonda, R. V., & Guldberg, R. E. (2014). Characterization of a composite injury model of severe lower limb bone and nerve trauma. Journal of Tissue Engineering and Regenerative Medicine, 8(6), 432–441. https://doi.org/10.1002/term.1537
Uhrig, Brent A., Isaac P. Clements, Joel D. Boerckel, Nathaniel Huebsch, Ravi V. Bellamkonda, and Robert E. Guldberg. “Characterization of a composite injury model of severe lower limb bone and nerve trauma.Journal of Tissue Engineering and Regenerative Medicine 8, no. 6 (June 2014): 432–41. https://doi.org/10.1002/term.1537.
Uhrig BA, Clements IP, Boerckel JD, Huebsch N, Bellamkonda RV, Guldberg RE. Characterization of a composite injury model of severe lower limb bone and nerve trauma. Journal of tissue engineering and regenerative medicine. 2014 Jun;8(6):432–41.
Uhrig, Brent A., et al. “Characterization of a composite injury model of severe lower limb bone and nerve trauma.Journal of Tissue Engineering and Regenerative Medicine, vol. 8, no. 6, June 2014, pp. 432–41. Epmc, doi:10.1002/term.1537.
Uhrig BA, Clements IP, Boerckel JD, Huebsch N, Bellamkonda RV, Guldberg RE. Characterization of a composite injury model of severe lower limb bone and nerve trauma. Journal of tissue engineering and regenerative medicine. 2014 Jun;8(6):432–441.
Journal cover image

Published In

Journal of tissue engineering and regenerative medicine

DOI

EISSN

1932-7005

ISSN

1932-6254

Publication Date

June 2014

Volume

8

Issue

6

Start / End Page

432 / 441

Related Subject Headings

  • X-Ray Microtomography
  • Trauma, Nervous System
  • Rats, Inbred Lew
  • Nerve Regeneration
  • Lower Extremity
  • In Vitro Techniques
  • Gait
  • Female
  • Electrophysiological Phenomena
  • Disease Models, Animal