Pauline Bléry1, Florent Espitalier2, Alexandra Hays3, Eléonore Crauste3, Christelle Demarquay4, Paul Pilet5, Sophie Sourice3, Jérôme Guicheux5, Olivier Malard2, Marc Benderitter4, Pierre Weiss6, Noëlle Mathieu4. 1. Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Faculté de Chirurgie Dentaire (Head: Prof. Y. Amouriq), Université de Nantes, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; IRCCyN, CNRS 6597, IVC (Head: Prof. Patrick Le Callet), Polytech'Nantes, rue Christian Pauc, 44306 Nantes Cedex 3, France; CHU Nantes, Pôle Hospitalo-Universitaire 4 OTONN (Head: Dr. G. Amador del Valle), 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1, France; Service d'Odontologie Restauratrice et Chirurgicale (Head: Prof. Y. Amouriq), CHU de Nantes, PHU4OTONN, 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1, France. Electronic address: pauline.blery@univ-nantes.fr. 2. Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; CHU Nantes, Pôle Hospitalo-Universitaire 4 OTONN (Head: Dr. G. Amador del Valle), 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1, France; Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale (Head: Prof. P. Bordure), CHU de Nantes, Pôle Hospitalo-Universiatire 4 OTONN, France. 3. Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France. 4. IRSN Institut de Radioprotection et de Sûreté Nucléaire, IRSN/PRP-HOM/SRBE/LR2I (Head: Dr. M. Benderitter), 31 avenue de la division Leclerc BP17, 92260 Fontenay aux Roses, France. 5. Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; CHU Nantes, Pôle Hospitalo-Universitaire 4 OTONN (Head: Dr. G. Amador del Valle), 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1, France. 6. Inserm U791 (Head: Prof. P. Weiss), LIOAD, Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; Faculté de Chirurgie Dentaire (Head: Prof. Y. Amouriq), Université de Nantes, 1 Place Alexis Ricordeau, 44042 Nantes Cedex 1, France; CHU Nantes, Pôle Hospitalo-Universitaire 4 OTONN (Head: Dr. G. Amador del Valle), 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1, France.
Abstract
OBJECTIVES: To develop an animal model of mandibular osteoradionecrosis (ORN) using a high-energy radiation source (as used in human therapeutics) and to assess the role of tooth extraction on ORN development. MATERIALS AND METHODS (STUDY DESIGN): Ten animals were irradiated with a single 35- or 50-Gy dose. Three weeks later, the second left mandibular molar was extracted from three animals in each group. Nine weeks after irradiation, the animals were euthanized, with an injection of contrast agent in the bloodstream to highlight vascularization. Mandibles were harvested and studied using micro-CT, histology, tartrate-resistant acid phosphatase activity and scanning electron microscopy. RESULTS: This study demonstrates that a single 50-Gy dose associated with molar extraction is necessary for ORN development. In these conditions, absence of healing of the mucosa and bone, dental effects, fibrosis, an increase in osteoclast activity and a decrease in vascularization were observed. We also determined that molar extraction increases the impact of the cellular effects of radiation. CONCLUSION: The mandibular ORN animal model was validated after 50-Gy irradiation and molar extraction. The results of this study therefore support an animal ORN model and tissue engineering strategies will now be developed to regenerate bone for patients with head and neck cancer.
OBJECTIVES: To develop an animal model of mandibular osteoradionecrosis (ORN) using a high-energy radiation source (as used in human therapeutics) and to assess the role of tooth extraction on ORN development. MATERIALS AND METHODS (STUDY DESIGN): Ten animals were irradiated with a single 35- or 50-Gy dose. Three weeks later, the second left mandibular molar was extracted from three animals in each group. Nine weeks after irradiation, the animals were euthanized, with an injection of contrast agent in the bloodstream to highlight vascularization. Mandibles were harvested and studied using micro-CT, histology, tartrate-resistant acid phosphatase activity and scanning electron microscopy. RESULTS: This study demonstrates that a single 50-Gy dose associated with molar extraction is necessary for ORN development. In these conditions, absence of healing of the mucosa and bone, dental effects, fibrosis, an increase in osteoclast activity and a decrease in vascularization were observed. We also determined that molar extraction increases the impact of the cellular effects of radiation. CONCLUSION: The mandibular ORN animal model was validated after 50-Gy irradiation and molar extraction. The results of this study therefore support an animal ORN model and tissue engineering strategies will now be developed to regenerate bone for patients with head and neck cancer.
Authors: Stacey L Piotrowski; Lindsay Wilson; Neeraja Dharmaraj; Amani Hamze; Ashley Clark; Ramesh Tailor; Lori R Hill; Stephen Lai; F Kurtis Kasper; Simon Young Journal: Tissue Eng Part C Methods Date: 2019-03 Impact factor: 3.056