Citation

Uhrig BA, Clements IP, Boerckel JD, Huebsch N, Bellamkonda RV, Guldberg RE. J. Tissue Eng. Regen. Med. 2014; 8(6): 432-441.

Affiliation

Parker H. Petit Institute for Bioengineering and Bioscience, George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.

Copyright

(Copyright © 2014, John Wiley and Sons)

DOI

10.1002/term.1537

PMID

22689452

Abstract

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. Copyright © 2012 John Wiley & Sons, Ltd.

Language: en