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Nonvascularized Bone Graft Reconstruction of the Irradiated Murine Mandible

An Analogue of Clinical Head and Neck Cancer Treatment

Urlaub, Kevin M., BS; Ettinger, Russell E., MD; Nelson, Noah S., MPH; Hoxie, Jessie M.; Snider, Alicia E., MD; Perosky, Joseph E., MS; Polyatskaya, Yekaterina, MD; Donneys, Alexis, MD, MS; Buchman, Steven R., MD, FACS

doi: 10.1097/SCS.0000000000005032
Scientific Foundations

Nonvascularized bone grafts (NBGs) represent a practical method of mandibular reconstruction that is precluded in head and neck cancer patients by the destructive effects of radiotherapy. Advances in tissue-engineering may restore NBGs as a viable surgical technique, but expeditious translation demands a small-animal model that approximates clinical practice. This study establishes a murine model of irradiated mandibular reconstruction using a segmental iliac crest NBG for the investigation of imperative bone healing strategies. Twenty-seven male isogenic Lewis rats were divided into 2 groups; control bone graft and irradiated bone graft (XBG). Additional Lewis rats served as graft donors. The XBG group was administered a fractionated dose of 35Gy. All rats underwent reconstruction of a segmental, critical-sized defect of the left hemi-mandible with a 5 mm NBG from the iliac crest, secured by a custom radiolucent plate. Following a 60-day recovery period, hemi-mandibles were evaluated for bony union, bone mineralization, and biomechanical strength (P < 0.05). Bony union rates were significantly reduced in the XBG group (42%) compared with controls (80%). Mandibles in the XBG group further demonstrated substantial radiation injury through significant reductions in all metrics of bone mineralization and biomechanical strength. These observations are consistent with the clinical sequelae of radiotherapy that limit NBGs to nonirradiated patients. This investigation provides a clinically relevant, quantitative model in which innovations in tissue engineering may be evaluated in the setting of radiotherapy to ultimately provide the advantages of NBGs to head and neck cancer patients and reconstructive surgeons.

Section of Plastic and Reconstructive Surgery, Michigan Medicine, Ann Arbor, MI.

Address correspondence and reprint requests to Steven R. Buchman, MD, FACS, Michigan Medicine, Pediatric Plastic Surgery Section, 4-730 C.S. Mott Children's Hospital, 1540 East Hospital Drive, Ann Arbor, MI 48109-4215; E-mail:

Received 14 June, 2018

Accepted 7 August, 2018

This work was supported by grants from the National Institutes of Health R01 (CA12587-06) to Dr SRB. Research reported in this publication was also supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number P30 AR069620.

The authors report no conflicts of interest.

© 2019 by Mutaz B. Habal, MD.