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Published in: Journal of Translational Medicine 1/2017

Open Access 01-12-2017 | Research

A rabbit model for experimental alveolar cleft grafting

Authors: Mohammad Kamal, Lars Andersson, Rene Tolba, Alexander Bartella, Felix Gremse, Frank Hölzle, Peter Kessler, Bernd Lethaus

Published in: Journal of Translational Medicine | Issue 1/2017

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Abstract

Objectives

The purpose of the present study was to develop an animal model for creating alveolar cleft defects with properly simulated clinical defect environment for tissue-engineered bone-substitute materials testing without compromising the health of the animal. Cleft creation surgery was aimed at creating a complete alveolar cleft with a wide bone defect with an epithelial lining (oral mucosa) overlying the cleft defect.

Methods

A postmortem skull of a New Zealand White (NZW) rabbit skull (Oryctolagus cuniculus) underwent an osteological and imaging survey. A pilot postmortem surgery was conducted to confirm the feasability of a surgical procedure and the defect was also radiologically confirmed and illustrated with micro-computed tomography. Then, a surgical in vivo model was tested and evaluated in 16 (n = 16) 8-week-old NZW rabbits to create in vivo alveolar cleft creation surgery.

Results

Clinical examination and imaging analysis 8 weeks after cleft creation surgery revealed the establishment of a wide skeletal defect extending to the nasal mucosa simulating alveolar clefts in all of the rabbits.

Conclusions

Our surgical technique was successful in creating a sizable and predictable model for bone grafting material testing. The model allows for simulating the cleft site environment and can be used to evaluate various bone grafting materials in regard to efficacy of osteogenesis and healing potential without compromising the health of the animal.
Literature
1.
go back to reference Rychlik D, Wójcicki P, Koźlik M. Osteoplasty of the alveolar cleft defect. Adv Clin Exp Med. 2012;21:255–62.PubMed Rychlik D, Wójcicki P, Koźlik M. Osteoplasty of the alveolar cleft defect. Adv Clin Exp Med. 2012;21:255–62.PubMed
2.
go back to reference Santiago PE, Schuster LA, Levy-Bercowski D. Management of the alveolar cleft. Clin Plast Surg. 2014;41:219–32.CrossRefPubMed Santiago PE, Schuster LA, Levy-Bercowski D. Management of the alveolar cleft. Clin Plast Surg. 2014;41:219–32.CrossRefPubMed
3.
go back to reference Seifeldin SA. Is alveolar cleft reconstruction still controversial? (review of literature). Saudi Dent J. 2016;28:3–11.CrossRefPubMed Seifeldin SA. Is alveolar cleft reconstruction still controversial? (review of literature). Saudi Dent J. 2016;28:3–11.CrossRefPubMed
4.
go back to reference Chung VH, Chen AY, Jeng LB, Kwan CC, Cheng SH, Chang SC. Engineered autologous bone marrow mesenchymal stem cells: alternative to cleft alveolar bone graft surgery. J Craniofac Surg. 2012;23:1558–63.CrossRefPubMed Chung VH, Chen AY, Jeng LB, Kwan CC, Cheng SH, Chang SC. Engineered autologous bone marrow mesenchymal stem cells: alternative to cleft alveolar bone graft surgery. J Craniofac Surg. 2012;23:1558–63.CrossRefPubMed
5.
go back to reference Gładysz D, Hozyasz KK. Stem cell regenerative therapy in alveolar cleft reconstruction. Arch Oral Biol. 2015;60:1517–32.CrossRefPubMed Gładysz D, Hozyasz KK. Stem cell regenerative therapy in alveolar cleft reconstruction. Arch Oral Biol. 2015;60:1517–32.CrossRefPubMed
6.
go back to reference Janssen NG, Weijs WLJ, Koole R, Rosenberg AJWP, Meijer GJ. Tissue engineering strategies for alveolar cleft reconstruction: a systematic review of the literature. Clin Oral Investig. 2014;18:219–26.CrossRefPubMed Janssen NG, Weijs WLJ, Koole R, Rosenberg AJWP, Meijer GJ. Tissue engineering strategies for alveolar cleft reconstruction: a systematic review of the literature. Clin Oral Investig. 2014;18:219–26.CrossRefPubMed
7.
go back to reference Kawata T, Kohno S, Fujita T, Sugiyama H, Tokimasa C, Kaku M, Tanne K. New biomaterials and methods for craniofacial bone defect: chondroid bone grafts in maxillary alveolar clefts. J Craniofac Genet Dev Biol. 2000;20:49–52.PubMed Kawata T, Kohno S, Fujita T, Sugiyama H, Tokimasa C, Kaku M, Tanne K. New biomaterials and methods for craniofacial bone defect: chondroid bone grafts in maxillary alveolar clefts. J Craniofac Genet Dev Biol. 2000;20:49–52.PubMed
8.
go back to reference Khojasteh A, Kheiri L, Motamedian SR, Nadjmi N. Regenerative medicine in the treatment of alveolar cleft defect: a systematic review of the literature. J Craniomaxillofac Surg. 2015;43:1608–13.CrossRefPubMed Khojasteh A, Kheiri L, Motamedian SR, Nadjmi N. Regenerative medicine in the treatment of alveolar cleft defect: a systematic review of the literature. J Craniomaxillofac Surg. 2015;43:1608–13.CrossRefPubMed
9.
go back to reference Caballero M, Morse JC, Halevi AE, Emodi O, Pharaon MR, Wood JS, van Aalst JA. Juvenile swine surgical alveolar cleft model to test novel autologous stem cell therapies. Tissue Eng Part C Methods. 2015;21:898–908.CrossRefPubMedPubMedCentral Caballero M, Morse JC, Halevi AE, Emodi O, Pharaon MR, Wood JS, van Aalst JA. Juvenile swine surgical alveolar cleft model to test novel autologous stem cell therapies. Tissue Eng Part C Methods. 2015;21:898–908.CrossRefPubMedPubMedCentral
10.
go back to reference de Ruiter A, Meijer G, Dormaar T, Janssen N, van der Bilt A, Slootweg P, de Bruijn J, van Rijn L, Koole R. β-TCP versus autologous bone for repair of alveolar clefts in a goat model. Cleft Palate Craniofac J. 2011;48:654–62.CrossRefPubMed de Ruiter A, Meijer G, Dormaar T, Janssen N, van der Bilt A, Slootweg P, de Bruijn J, van Rijn L, Koole R. β-TCP versus autologous bone for repair of alveolar clefts in a goat model. Cleft Palate Craniofac J. 2011;48:654–62.CrossRefPubMed
11.
go back to reference el-Bokle D, Smith SJ, Germane N, Sharawy M. New technique for creating permanent experimental alveolar clefts in a rabbit model. Cleft Palate Craniofac J. 1993;30:542–7.CrossRefPubMed el-Bokle D, Smith SJ, Germane N, Sharawy M. New technique for creating permanent experimental alveolar clefts in a rabbit model. Cleft Palate Craniofac J. 1993;30:542–7.CrossRefPubMed
12.
go back to reference El-Deeb M, Horswell B, Waite DE. A primate model for producing experimental alveolar cleft defects. J Oral Maxillofac Surg. 1985;43:523–7.CrossRefPubMed El-Deeb M, Horswell B, Waite DE. A primate model for producing experimental alveolar cleft defects. J Oral Maxillofac Surg. 1985;43:523–7.CrossRefPubMed
13.
go back to reference Gritli-Linde A. The mouse as a developmental model for cleft lip and palate research. Front Oral Biol. 2012;16:32–51.CrossRefPubMed Gritli-Linde A. The mouse as a developmental model for cleft lip and palate research. Front Oral Biol. 2012;16:32–51.CrossRefPubMed
14.
go back to reference Ishii Y. Experimental study of secondary bone graft of alveolar clefts using bone morphogenetic protein (BMP). Kokubyo Gakkai Zasshi. 2001;68:111–24.CrossRefPubMed Ishii Y. Experimental study of secondary bone graft of alveolar clefts using bone morphogenetic protein (BMP). Kokubyo Gakkai Zasshi. 2001;68:111–24.CrossRefPubMed
15.
go back to reference Liang L, Liu C. Trans-sutural distraction osteogenesis for alveolar cleft repair: an experimental canine study. Cleft Palate Craniofac J. 2012;49:701–7.CrossRefPubMed Liang L, Liu C. Trans-sutural distraction osteogenesis for alveolar cleft repair: an experimental canine study. Cleft Palate Craniofac J. 2012;49:701–7.CrossRefPubMed
16.
go back to reference Liao LS, Tan Z, Zheng Q, Wu J, Shi B, He X, Meng T, Lu DW, Wang Y, Li S. Animal experimental study on repairing alveolar clefts by using rectilinear distraction osteogenesis. J Plast Reconstr Aesthet Surg. 2009;62:1573–9.CrossRefPubMed Liao LS, Tan Z, Zheng Q, Wu J, Shi B, He X, Meng T, Lu DW, Wang Y, Li S. Animal experimental study on repairing alveolar clefts by using rectilinear distraction osteogenesis. J Plast Reconstr Aesthet Surg. 2009;62:1573–9.CrossRefPubMed
17.
go back to reference Mostafa NZ, Doschak MR, Major PW, Talwar R. Reliable critical sized defect rodent model for cleft palate research. J Craniomaxillofac Surg. 2014;42:1840–6.CrossRefPubMed Mostafa NZ, Doschak MR, Major PW, Talwar R. Reliable critical sized defect rodent model for cleft palate research. J Craniomaxillofac Surg. 2014;42:1840–6.CrossRefPubMed
18.
go back to reference Nguyen PD, Lin CD, Allori AC, Ricci JL, Saadeh PB, Warren SM. Establishment of a critical-sized alveolar defect in the rat: a model for human gingivoperiosteoplasty. Plast Reconstr Surg. 2009;123:817–25.CrossRefPubMed Nguyen PD, Lin CD, Allori AC, Ricci JL, Saadeh PB, Warren SM. Establishment of a critical-sized alveolar defect in the rat: a model for human gingivoperiosteoplasty. Plast Reconstr Surg. 2009;123:817–25.CrossRefPubMed
19.
go back to reference Papadopoulos MA, Papadopulos NA, Jannowitz C, Boettcher P, Henke J, Stolla R, Zeilhofer HF, Kovacs L, Biemer E. Three-dimensional cephalometric evaluation of maxillary growth following in utero repair of cleft lip and alveolar-like defects in the mid-gestational sheep model. Fetal Diagn Ther. 2006;21:105–14.CrossRefPubMed Papadopoulos MA, Papadopulos NA, Jannowitz C, Boettcher P, Henke J, Stolla R, Zeilhofer HF, Kovacs L, Biemer E. Three-dimensional cephalometric evaluation of maxillary growth following in utero repair of cleft lip and alveolar-like defects in the mid-gestational sheep model. Fetal Diagn Ther. 2006;21:105–14.CrossRefPubMed
20.
go back to reference Pilanci O, Cinar C, Kuvat SV, Altintas M, Guzel Z, Kilic A. Effects of hydroxyapatite on bone graft resorption in an experimental model of maxillary alveolar arch defects. Arch Clin Exp Surg. 2013;2:170–5.CrossRef Pilanci O, Cinar C, Kuvat SV, Altintas M, Guzel Z, Kilic A. Effects of hydroxyapatite on bone graft resorption in an experimental model of maxillary alveolar arch defects. Arch Clin Exp Surg. 2013;2:170–5.CrossRef
21.
go back to reference Raposo-Amaral CE, Kobayashi GS, Almeida AB, Bueno DF, Freitas FR, Vulcano LC, Passos-Bueno MR, Alonso N. Alveolar osseous defect in rat for cell therapy: preliminary report. Acta Cir Bras. 2010;25:313–7.CrossRefPubMed Raposo-Amaral CE, Kobayashi GS, Almeida AB, Bueno DF, Freitas FR, Vulcano LC, Passos-Bueno MR, Alonso N. Alveolar osseous defect in rat for cell therapy: preliminary report. Acta Cir Bras. 2010;25:313–7.CrossRefPubMed
22.
go back to reference Sawada Y, Hokugo A, Nishiura A, Hokugo R, Matsumoto N, Morita S, Tabata Y. A trial of alveolar cleft bone regeneration by controlled release of bone morphogenetic protein: an experimental study in rabbits. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108:812–20.CrossRefPubMed Sawada Y, Hokugo A, Nishiura A, Hokugo R, Matsumoto N, Morita S, Tabata Y. A trial of alveolar cleft bone regeneration by controlled release of bone morphogenetic protein: an experimental study in rabbits. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108:812–20.CrossRefPubMed
23.
go back to reference Wu L-L, Zhao Y, Chen C. Establishment of the animal model with unilateral alveolar cleft and its effect on the nose growth. Zhonghua Zheng Xing Wai Ke Za Zhi. 2010;26:39–42.PubMed Wu L-L, Zhao Y, Chen C. Establishment of the animal model with unilateral alveolar cleft and its effect on the nose growth. Zhonghua Zheng Xing Wai Ke Za Zhi. 2010;26:39–42.PubMed
24.
go back to reference Xu Y, Sun J, Chen Z. Establishment of a rat model for alveolar cleft with bone wax. J Oral Maxillofac Surg. 2015;73:733.e1–10.CrossRef Xu Y, Sun J, Chen Z. Establishment of a rat model for alveolar cleft with bone wax. J Oral Maxillofac Surg. 2015;73:733.e1–10.CrossRef
25.
go back to reference Harling TR, Stelnicki EJ, Hedrick MH, Longaker MT. In utero models of craniofacial surgery. World J Surg. 2003;27:108–16.CrossRefPubMed Harling TR, Stelnicki EJ, Hedrick MH, Longaker MT. In utero models of craniofacial surgery. World J Surg. 2003;27:108–16.CrossRefPubMed
26.
go back to reference Hedrick MH, Rice HE, Vander Wall KJ, Adzick NS, Harrison MR, Siebert J, Hoffman WY, Longaker MT. Delayed in utero repair of surgically created fetal cleft lip and palate. Plast Reconstr Surg. 1996;97:900–5.CrossRefPubMed Hedrick MH, Rice HE, Vander Wall KJ, Adzick NS, Harrison MR, Siebert J, Hoffman WY, Longaker MT. Delayed in utero repair of surgically created fetal cleft lip and palate. Plast Reconstr Surg. 1996;97:900–5.CrossRefPubMed
27.
go back to reference Wenghoefer MHO, Deprest J, Goetz W, Kuijpers-Jagtman AM, Bergé S. Prenatal cleft lip and maxillary alveolar defect repair in a 2-step fetal lamb model. J Oral Maxillofac Surg. 2007;65:2479–86.CrossRefPubMed Wenghoefer MHO, Deprest J, Goetz W, Kuijpers-Jagtman AM, Bergé S. Prenatal cleft lip and maxillary alveolar defect repair in a 2-step fetal lamb model. J Oral Maxillofac Surg. 2007;65:2479–86.CrossRefPubMed
28.
go back to reference Igawa HH, Ohura T, Iwao F, Yamamoto Y, Fujioka H. Intrauterine repair of cleft lip in mouse fetuses. Congenit Anom. 1991;31:95–100.CrossRef Igawa HH, Ohura T, Iwao F, Yamamoto Y, Fujioka H. Intrauterine repair of cleft lip in mouse fetuses. Congenit Anom. 1991;31:95–100.CrossRef
29.
go back to reference Leitao JM, Pereira LA, Gonçalves FL, Schmidt AF, Sbragia L. The ideal timing for experimental cleft lip creation. Cleft Palate Craniofac J. 2011;48:38–43.CrossRefPubMed Leitao JM, Pereira LA, Gonçalves FL, Schmidt AF, Sbragia L. The ideal timing for experimental cleft lip creation. Cleft Palate Craniofac J. 2011;48:38–43.CrossRefPubMed
30.
go back to reference Schardein J, Petrere J, Hentz D, Camp R, Kurtz S. Cannibalistic traits observed in rats treated with a teratogen. Lab Anim. 1978;12:81–3.CrossRefPubMed Schardein J, Petrere J, Hentz D, Camp R, Kurtz S. Cannibalistic traits observed in rats treated with a teratogen. Lab Anim. 1978;12:81–3.CrossRefPubMed
31.
go back to reference Li Y, Chen S-K, Li L, Qin L, Wang X-L, Lai Y-X. Bone defect animal models for testing efficacy of bone substitute biomaterials. J Orthop Transl. 2015;3:95–104. Li Y, Chen S-K, Li L, Qin L, Wang X-L, Lai Y-X. Bone defect animal models for testing efficacy of bone substitute biomaterials. J Orthop Transl. 2015;3:95–104.
32.
go back to reference Mapara M, Thomas BS, Bhat K. Rabbit as an animal model for experimental research. Dent Res J. 2012;9:111–8.CrossRef Mapara M, Thomas BS, Bhat K. Rabbit as an animal model for experimental research. Dent Res J. 2012;9:111–8.CrossRef
33.
go back to reference Pearce A, Richards R, Milz S, Schneider E, Pearce S. Animal models for implant biomaterial research in bone: a review. Eur Cell Mater. 2007;13:1–10.CrossRefPubMed Pearce A, Richards R, Milz S, Schneider E, Pearce S. Animal models for implant biomaterial research in bone: a review. Eur Cell Mater. 2007;13:1–10.CrossRefPubMed
34.
go back to reference Wang X, Mabrey JD, Agrawal CM. An interspecies comparison of bone fracture properties. Biomed Mater Eng. 1998;8:1–10.PubMed Wang X, Mabrey JD, Agrawal CM. An interspecies comparison of bone fracture properties. Biomed Mater Eng. 1998;8:1–10.PubMed
35.
go back to reference Al-Asfour A, Andersson L, Kamal M, Joseph B. New bone formation around xenogenic dentin grafts to rabbit tibia marrow. Dent Traumatol. 2013;29:455–60.CrossRefPubMed Al-Asfour A, Andersson L, Kamal M, Joseph B. New bone formation around xenogenic dentin grafts to rabbit tibia marrow. Dent Traumatol. 2013;29:455–60.CrossRefPubMed
36.
go back to reference Andersson L, Ramzi A, Joseph B. Studies on dentin grafts to bone defects in rabbit tibia and mandible; development of an experimental model. Dent Traumatol. 2009;25:78–83.CrossRefPubMed Andersson L, Ramzi A, Joseph B. Studies on dentin grafts to bone defects in rabbit tibia and mandible; development of an experimental model. Dent Traumatol. 2009;25:78–83.CrossRefPubMed
37.
go back to reference Kolk A, Handschel J, Drescher W, Rothamel D, Kloss F, Blessmann M, Heiland M, Wolff KD, Smeets R. Current trends and future perspectives of bone substitute materials—from space holders to innovative biomaterials. J Craniomaxillofac Surg. 2012;40:706–18.CrossRefPubMed Kolk A, Handschel J, Drescher W, Rothamel D, Kloss F, Blessmann M, Heiland M, Wolff KD, Smeets R. Current trends and future perspectives of bone substitute materials—from space holders to innovative biomaterials. J Craniomaxillofac Surg. 2012;40:706–18.CrossRefPubMed
39.
go back to reference Kim J-H, Moon H-J, Kim T-H, Jo J-M, Yang SH, Naskar D, Kundu SC, Chrzanowski W, Kim H-W. A novel in vivo platform for studying alveolar bone regeneration in rat. J Tissue Eng. 2013;4:2041731413517705.CrossRefPubMedPubMedCentral Kim J-H, Moon H-J, Kim T-H, Jo J-M, Yang SH, Naskar D, Kundu SC, Chrzanowski W, Kim H-W. A novel in vivo platform for studying alveolar bone regeneration in rat. J Tissue Eng. 2013;4:2041731413517705.CrossRefPubMedPubMedCentral
40.
go back to reference Puumanen K, Kellomaki M, Ritsila V, Bohling T, Tormala P, Waris T, Ashammakhi N. A novel bioabsorbable composite membrane of polyactive 70/30 and bioactive glass number 13–93 in repair of experimental maxillary alveolar cleft defects. J Biomed Mater Res B Appl Biomater. 2005;75:25–33.CrossRefPubMed Puumanen K, Kellomaki M, Ritsila V, Bohling T, Tormala P, Waris T, Ashammakhi N. A novel bioabsorbable composite membrane of polyactive 70/30 and bioactive glass number 13–93 in repair of experimental maxillary alveolar cleft defects. J Biomed Mater Res B Appl Biomater. 2005;75:25–33.CrossRefPubMed
41.
go back to reference Takano-Yamamoto T, Kawakami M, Sakuda M. Defects of the rat premaxilla as a model of alveolar clefts for testing bone-inductive agents. J Oral Maxillofac Surg. 1993;51:887–91.CrossRefPubMed Takano-Yamamoto T, Kawakami M, Sakuda M. Defects of the rat premaxilla as a model of alveolar clefts for testing bone-inductive agents. J Oral Maxillofac Surg. 1993;51:887–91.CrossRefPubMed
42.
go back to reference Bykowski MR, Naran S, Winger DG, Losee JE. The rate of oronasal fistula following primary cleft palate surgery: a meta-analysis. Cleft Palate Craniofac J. 2015;52:e81–7.CrossRefPubMed Bykowski MR, Naran S, Winger DG, Losee JE. The rate of oronasal fistula following primary cleft palate surgery: a meta-analysis. Cleft Palate Craniofac J. 2015;52:e81–7.CrossRefPubMed
43.
go back to reference Maslamani M, Almusawi A, Joseph B, Gabato S, Andersson L. An experimental model for studies on delayed tooth replantation and ankylosis in rabbits. Dent Traumatol. 2016;32:443–9.CrossRefPubMed Maslamani M, Almusawi A, Joseph B, Gabato S, Andersson L. An experimental model for studies on delayed tooth replantation and ankylosis in rabbits. Dent Traumatol. 2016;32:443–9.CrossRefPubMed
44.
go back to reference Directive C. 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. Off J Eur Commun. 1986;29:L358. Directive C. 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. Off J Eur Commun. 1986;29:L358.
Metadata
Title
A rabbit model for experimental alveolar cleft grafting
Authors
Mohammad Kamal
Lars Andersson
Rene Tolba
Alexander Bartella
Felix Gremse
Frank Hölzle
Peter Kessler
Bernd Lethaus
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2017
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-017-1155-2

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