Abstract
BackgroundRadiation therapy is widely employed in the treatment of head and neck cancer. Adverse effects of therapeutic irradiation include delayed bone healing after dental extraction or impaired bone regeneration at the irradiated bony defect. Development of a reliable experimental model may be beneficial to study tissue regeneration in the irradiated field. The current study aimed to develop a relevant animal model of post-radiation cranial bone defect.MethodsA lead shielding block was designed for selective external irradiation of the mouse calvaria. Critical-size calvarial defect was created 2 weeks after the irradiation. The defect was filled with a collagen scaffold, with or without incorporation of bone morphogenetic protein 2 (BMP-2) (1 μg/ml). The non-irradiated mice treated with or without BMP-2-included scaffold served as control. Four weeks after the surgery, the specimens were harvested and the degree of bone formation was evaluated by histological and radiographical examinations.ResultsBMP-2-treated scaffold yielded significant bone regeneration in the mice calvarial defects. However, a single fraction of external irradiation was observed to eliminate the bone regeneration capacity of the BMP-2-incorporated scaffold without influencing the survival of the animals.ConclusionThe current study established an efficient model for post-radiation cranial bone regeneration and can be applied for evaluating the robust bone formation system using various chemokines or agents in unfavorable, demanding radiation-related bone defect models.
Highlights
Radiation therapy is widely employed in the treatment of head and neck cancer, which may be performed before or after resection of the tumor
Microvascular free tissue transfer has been considered the gold standard for bone reconstruction in the field of irradiation, as it overcomes the limitations of non-vascularized grafts [10,11,12]
The current study aimed to develop a relevant mouse model of post-radiation cranial bone defect
Summary
Adverse effects of therapeutic irradiation include delayed bone healing after dental extraction or impaired bone regeneration at the irradiated bony defect. Adverse effects of therapeutic irradiation include delayed bone healing after dental extraction or impaired bone regeneration in the resultant bony defects [1]. Irradiation causes bone marrow depression and mesenchymal cell apoptosis [4] as well as delayed wound healing, tissue inflammation, There are limited therapeutic options for reconstruction of bone damaged by irradiation due to fibrosis, cell necrosis, and severe impairment of vascular supply. Microvascular free tissue transfer has been considered the gold standard for bone reconstruction in the field of irradiation, as it overcomes the limitations of non-vascularized grafts [10,11,12].
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