J reconstr Microsurg
DOI: 10.1055/s-0037-1607322
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs

Ahmad Eweida1, 2, *, Ibrahim Fathi1, *, Ahmed M. Eltawila3, Ahmad M. Elsherif1, Yasser Elkerm4, Leila Harhaus2, Ulrich Kneser2, Mahmoud F. Sakr1
  • 1Head, Neck and Endocrine Surgery Unit, Department of Surgery, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
  • 2Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
  • 3Department of Materials Science, Institute of Graduate Studies and Research, University of Alexandria, Alexandria, Egypt
  • 4Department of Radiation and Clinical Oncology, Medical Research Institute, University of Alexandria, Alexandria, Egypt
Further Information

Publication History

19 June 2017

24 August 2017

Publication Date:
30 October 2017 (eFirst)


Background Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.

Methods We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. The constructs were removed 20 days after irradiation and subjected to histological and immunohistochemical analysis for vascularization, bone formation, apoptosis, and cellular proliferation.

Results The vascularized constructs showed homogenous vascularization and bone formation both in their central and peripheral regions. Although vascularity, proliferation, and apoptosis were similar between central and peripheral regions of the constructs, significantly more bone was formed in the central regions of the constructs.

Conclusion The study shows for the first time the pattern of bone formation in AVTECs after irradiation using doses comparable to those applied after head and neck cancer. Axial vascularization probably enhances the osteoinductive properties in the central regions of AVTECs after irradiation.

* Both these authors have contributed equally to the article.