Abstract
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.
Keywords
bone regeneration - irradiation - tissue engineering - regenerative medicine - axial
vascularization
