Skip to main content
Top
Published in: Maxillofacial Plastic and Reconstructive Surgery 1/2018

Open Access 01-12-2018 | Research

Development of an experimental model for radiation-induced inhibition of cranial bone regeneration

Authors: Hong-Moon Jung, Jeong-Eun Lee, Seoung-Jun Lee, Jung-Tae Lee, Tae-Yub Kwon, Tae-Geon Kwon

Published in: Maxillofacial Plastic and Reconstructive Surgery | Issue 1/2018

Login to get access

Abstract

Background

Radiation 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.

Methods

A 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.

Results

BMP-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.

Conclusion

The 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.
Literature
1.
go back to reference Dimery IW, Hong WK (1993) Overview of combined modality therapies for head and neck cancer. J Natl Cancer Inst 85:95–111CrossRef Dimery IW, Hong WK (1993) Overview of combined modality therapies for head and neck cancer. J Natl Cancer Inst 85:95–111CrossRef
2.
go back to reference Omolehinwa TT, Akintoye SO (2016) Chemical and radiation-associated jaw lesions. Dent Clin N Am 60:265–277CrossRef Omolehinwa TT, Akintoye SO (2016) Chemical and radiation-associated jaw lesions. Dent Clin N Am 60:265–277CrossRef
3.
go back to reference Jegoux F, Malard O, Goyenvalle E, Aguado E, Daculsi G (2010) Radiation effects on bone healing and reconstruction: interpretation of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:173–184CrossRef Jegoux F, Malard O, Goyenvalle E, Aguado E, Daculsi G (2010) Radiation effects on bone healing and reconstruction: interpretation of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:173–184CrossRef
4.
go back to reference van Os R, Thames HD, Konings AW, Down JD (1993) Radiation dose-fractionation and dose-rate relationships for long-term repopulating hemopoietic stem cells in a murine bone marrow transplant model. Radiat Res 136:118–125CrossRef van Os R, Thames HD, Konings AW, Down JD (1993) Radiation dose-fractionation and dose-rate relationships for long-term repopulating hemopoietic stem cells in a murine bone marrow transplant model. Radiat Res 136:118–125CrossRef
5.
go back to reference Muller K, Meineke V (2010) Advances in the management of localized radiation injuries. Health Phys 98:843–850CrossRef Muller K, Meineke V (2010) Advances in the management of localized radiation injuries. Health Phys 98:843–850CrossRef
6.
go back to reference Delanian S, Lefaix JL (2004) The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. Radiother Oncol 73:119–131CrossRef Delanian S, Lefaix JL (2004) The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. Radiother Oncol 73:119–131CrossRef
7.
go back to reference Kim CM, Park MH, Yun SW, Kim JW (2015) Treatment of pathologic fracture following postoperative radiation therapy: clinical study. Maxillofac Plast Reconstr Surg 37:31CrossRef Kim CM, Park MH, Yun SW, Kim JW (2015) Treatment of pathologic fracture following postoperative radiation therapy: clinical study. Maxillofac Plast Reconstr Surg 37:31CrossRef
8.
go back to reference Moura LB, Carvalho PH, Xavier CB, Post LK, Torriani MA, Santagata M et al (2016) Autogenous non-vascularized bone graft in segmental mandibular reconstruction: a systematic review. Int J Oral Maxillofac Surg 45:1388–1394CrossRef Moura LB, Carvalho PH, Xavier CB, Post LK, Torriani MA, Santagata M et al (2016) Autogenous non-vascularized bone graft in segmental mandibular reconstruction: a systematic review. Int J Oral Maxillofac Surg 45:1388–1394CrossRef
9.
go back to reference Kim JW, Hwang JH, Ahn KM (2016) Fibular flap for mandible reconstruction in osteoradionecrosis of the jaw: selection criteria of fibula flap. Maxillofac Plast Reconstr Surg 38:46CrossRef Kim JW, Hwang JH, Ahn KM (2016) Fibular flap for mandible reconstruction in osteoradionecrosis of the jaw: selection criteria of fibula flap. Maxillofac Plast Reconstr Surg 38:46CrossRef
10.
go back to reference Paderno A, Piazza C, Bresciani L, Vella R, Nicolai P (2016) Microvascular head and neck reconstruction after (chemo)radiation: facts and prejudices. Curr Opin Otolaryngol Head Neck Surg 24:83–90CrossRef Paderno A, Piazza C, Bresciani L, Vella R, Nicolai P (2016) Microvascular head and neck reconstruction after (chemo)radiation: facts and prejudices. Curr Opin Otolaryngol Head Neck Surg 24:83–90CrossRef
11.
go back to reference Kim MG, Lee ST, Park JY, Choi SW (2015) Reconstruction with fibular osteocutaneous free flap in patients with mandibular osteoradionecrosis. Maxillofac Plast Reconstr Surg 37:7CrossRef Kim MG, Lee ST, Park JY, Choi SW (2015) Reconstruction with fibular osteocutaneous free flap in patients with mandibular osteoradionecrosis. Maxillofac Plast Reconstr Surg 37:7CrossRef
12.
go back to reference Pogrel MA, Podlesh S, Anthony JP, Alexander J (1997) A comparison of vascularized and nonvascularized bone grafts for reconstruction of mandibular continuity defects. J Oral Maxillofac Surg 55:1200–1206CrossRef Pogrel MA, Podlesh S, Anthony JP, Alexander J (1997) A comparison of vascularized and nonvascularized bone grafts for reconstruction of mandibular continuity defects. J Oral Maxillofac Surg 55:1200–1206CrossRef
13.
go back to reference Wang Z, Qiu W, Mendenhall WM (2003) Influence of radiation therapy on reconstructive flaps after radical resection of head and neck cancer. Int J Oral Maxillofac Surg 32:35–38CrossRef Wang Z, Qiu W, Mendenhall WM (2003) Influence of radiation therapy on reconstructive flaps after radical resection of head and neck cancer. Int J Oral Maxillofac Surg 32:35–38CrossRef
14.
go back to reference Beckman JA, Thakore A, Kalinowski BH, Harris JR, Creager MA (2001) Radiation therapy impairs endothelium-dependent vasodilation in humans. J Am Coll Cardiol 37:761–765CrossRef Beckman JA, Thakore A, Kalinowski BH, Harris JR, Creager MA (2001) Radiation therapy impairs endothelium-dependent vasodilation in humans. J Am Coll Cardiol 37:761–765CrossRef
15.
go back to reference Wurzler KK, DeWeese TL, Sebald W, Reddi AH (1998) Radiation-induced impairment of bone healing can be overcome by recombinant human bone morphogenetic protein-2. J Craniofac Surg 9:131–137CrossRef Wurzler KK, DeWeese TL, Sebald W, Reddi AH (1998) Radiation-induced impairment of bone healing can be overcome by recombinant human bone morphogenetic protein-2. J Craniofac Surg 9:131–137CrossRef
16.
go back to reference Nussenbaum B, Rutherford RB, Krebsbach PH (2005) Bone regeneration in cranial defects previously treated with radiation. Laryngoscope 115:1170–1177CrossRef Nussenbaum B, Rutherford RB, Krebsbach PH (2005) Bone regeneration in cranial defects previously treated with radiation. Laryngoscope 115:1170–1177CrossRef
17.
go back to reference Kinsella CR Jr, Macisaac ZM, Cray JJ, Smith DM, Rottgers SA, Mooney MP et al (2012) Novel animal model of calvarial defect: part III. Reconstruction of an irradiated wound with rhBMP-2. Plast Reconstr Surg 130:643e–650eCrossRef Kinsella CR Jr, Macisaac ZM, Cray JJ, Smith DM, Rottgers SA, Mooney MP et al (2012) Novel animal model of calvarial defect: part III. Reconstruction of an irradiated wound with rhBMP-2. Plast Reconstr Surg 130:643e–650eCrossRef
18.
go back to reference Hu WW, Ward BB, Wang Z, Krebsbach PH (2010) Bone regeneration in defects compromised by radiotherapy. J Dent Res 89:77–81CrossRef Hu WW, Ward BB, Wang Z, Krebsbach PH (2010) Bone regeneration in defects compromised by radiotherapy. J Dent Res 89:77–81CrossRef
19.
go back to reference Woo M, Nordal R (2006) Commissioning and evaluation of a new commercial small rodent x-ray irradiator. Biomed Imaging Interv J 2:e10CrossRef Woo M, Nordal R (2006) Commissioning and evaluation of a new commercial small rodent x-ray irradiator. Biomed Imaging Interv J 2:e10CrossRef
20.
go back to reference Sugiyama K, Yamaguchi M, Kuroda J, Takanashi M, Ishikawa Y, Fujii H et al (2009) Improvement of radiation-induced healing delay by etanercept treatment in rat arteries. Cancer Sci 100:1550–1555CrossRef Sugiyama K, Yamaguchi M, Kuroda J, Takanashi M, Ishikawa Y, Fujii H et al (2009) Improvement of radiation-induced healing delay by etanercept treatment in rat arteries. Cancer Sci 100:1550–1555CrossRef
21.
go back to reference Espitalier F, Vinatier C, Lerouxel E, Guicheux J, Pilet P, Moreau F et al (2009) A comparison between bone reconstruction following the use of mesenchymal stem cells and total bone marrow in association with calcium phosphate scaffold in irradiated bone. Biomaterials 30:763–769CrossRef Espitalier F, Vinatier C, Lerouxel E, Guicheux J, Pilet P, Moreau F et al (2009) A comparison between bone reconstruction following the use of mesenchymal stem cells and total bone marrow in association with calcium phosphate scaffold in irradiated bone. Biomaterials 30:763–769CrossRef
22.
go back to reference Kirkby C, Ghasroddashti E, Kovalchuk A, Kolb B, Kovalchuk O (2013) Monte Carlo-based dose reconstruction in a rat model for scattered ionizing radiation investigations. Int J Radiat Biol 89:741–749CrossRef Kirkby C, Ghasroddashti E, Kovalchuk A, Kolb B, Kovalchuk O (2013) Monte Carlo-based dose reconstruction in a rat model for scattered ionizing radiation investigations. Int J Radiat Biol 89:741–749CrossRef
23.
go back to reference Williams JP, Brown SL, Georges GE, Hauer-Jensen M, Hill RP, Huser AK et al (2010) Animal models for medical countermeasures to radiation exposure. Radiat Res 173:557–578CrossRef Williams JP, Brown SL, Georges GE, Hauer-Jensen M, Hill RP, Huser AK et al (2010) Animal models for medical countermeasures to radiation exposure. Radiat Res 173:557–578CrossRef
24.
go back to reference Singh VK, Newman VL, Berg AN, MacVittie TJ (2015) Animal models for acute radiation syndrome drug discovery. Expert Opin Drug Discov 10:497–517CrossRef Singh VK, Newman VL, Berg AN, MacVittie TJ (2015) Animal models for acute radiation syndrome drug discovery. Expert Opin Drug Discov 10:497–517CrossRef
25.
go back to reference King MA, Casarett GW, Weber DA (1979) A study of irradiated bone: I. histopathologic and physiologic changes. J Nucl Med 20:1142–1149PubMed King MA, Casarett GW, Weber DA (1979) A study of irradiated bone: I. histopathologic and physiologic changes. J Nucl Med 20:1142–1149PubMed
26.
go back to reference Deshpande SS, Donneys A, Farberg AS, Tchanque-Fossuo CN, Felice PA, Buchman SR (2014) Quantification and characterization of radiation-induced changes to mandibular vascularity using micro-computed tomography. Ann Plast Surg 72:100–103CrossRef Deshpande SS, Donneys A, Farberg AS, Tchanque-Fossuo CN, Felice PA, Buchman SR (2014) Quantification and characterization of radiation-induced changes to mandibular vascularity using micro-computed tomography. Ann Plast Surg 72:100–103CrossRef
27.
go back to reference Sawada K, Fujioka-Kobayashi M, Kobayashi E, Bromme JO, Schaller B, Miron RJ (2016) In vitro effects of 0 to 120 grays of irradiation on bone viability and release of growth factors. BMC Oral Health 17:4CrossRef Sawada K, Fujioka-Kobayashi M, Kobayashi E, Bromme JO, Schaller B, Miron RJ (2016) In vitro effects of 0 to 120 grays of irradiation on bone viability and release of growth factors. BMC Oral Health 17:4CrossRef
28.
go back to reference Doyle JW, Li YQ, Salloum A, FitzGerald TJ, Walton RL (1996) The effects of radiation on neovascularization in a rat model. Plast Reconstr Surg 98:129–135 discussion 36-9CrossRef Doyle JW, Li YQ, Salloum A, FitzGerald TJ, Walton RL (1996) The effects of radiation on neovascularization in a rat model. Plast Reconstr Surg 98:129–135 discussion 36-9CrossRef
29.
go back to reference Springer IN, Niehoff P, Acil Y, Marget M, Lange A, Warnke PH et al (2008) BMP-2 and bFGF in an irradiated bone model. J Craniomaxillofac Surg 36:210–217CrossRef Springer IN, Niehoff P, Acil Y, Marget M, Lange A, Warnke PH et al (2008) BMP-2 and bFGF in an irradiated bone model. J Craniomaxillofac Surg 36:210–217CrossRef
30.
go back to reference Ryu SH, Park JH, Jeong ES, Choi SY, Ham SH, Park JI et al (2016) Establishment of a mouse model of 70% lethal dose by total-body irradiation. Lab Anim Res 32:116–121CrossRef Ryu SH, Park JH, Jeong ES, Choi SY, Ham SH, Park JI et al (2016) Establishment of a mouse model of 70% lethal dose by total-body irradiation. Lab Anim Res 32:116–121CrossRef
31.
go back to reference Rivina L, Schiestl R (2012) Mouse models for efficacy testing of agents against radiation carcinogenesis - a literature review. Int J Environ Res Public Health 10:107–143CrossRef Rivina L, Schiestl R (2012) Mouse models for efficacy testing of agents against radiation carcinogenesis - a literature review. Int J Environ Res Public Health 10:107–143CrossRef
32.
go back to reference Wernle JD, Damron TA, Allen MJ, Mann KA (2010) Local irradiation alters bone morphology and increases bone fragility in a mouse model. J Biomech 43:2738–2746CrossRef Wernle JD, Damron TA, Allen MJ, Mann KA (2010) Local irradiation alters bone morphology and increases bone fragility in a mouse model. J Biomech 43:2738–2746CrossRef
Metadata
Title
Development of an experimental model for radiation-induced inhibition of cranial bone regeneration
Authors
Hong-Moon Jung
Jeong-Eun Lee
Seoung-Jun Lee
Jung-Tae Lee
Tae-Yub Kwon
Tae-Geon Kwon
Publication date
01-12-2018
Publisher
Springer Berlin Heidelberg
Published in
Maxillofacial Plastic and Reconstructive Surgery / Issue 1/2018
Electronic ISSN: 2288-8586
DOI
https://doi.org/10.1186/s40902-018-0173-1

Other articles of this Issue 1/2018

Maxillofacial Plastic and Reconstructive Surgery 1/2018 Go to the issue