Skip to main content

Advertisement

Log in

Application of tissue-engineered bone grafts for alveolar cleft osteoplasty in a rodent model

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objectives

The clinical standard for alveolar cleft osteoplasty is augmentation with autologous bone being available in limited amounts and might be associated with donor site morbidity. The aim of the present study was the creation of tissue-engineered bone grafts and their in vivo evaluation regarding their potential to promote osteogenesis in an alveolar cleft model.

Materials and methods

Artificial bone defects with a diameter of 3.3 mm were created surgically in the palate of 84 adult Lewis rats. Four experimental groups (n = 21) were examined: bovine hydroxyl apatite/collagen (bHA) without cells, bHA with undifferentiated mesenchymal stromal cells (MSC), bHA with osteogenically differentiated MSC. In a control group, the defect remained empty. After 6, 9 and 12 weeks, the remaining defect volume was assessed by cone beam computed tomography. Histologically, the remaining defect width and percentage of bone formation was quantified.

Results

After 12 weeks, the remaining defect width was 60.1% for bHA, 74.7% for bHA with undifferentiated MSC and 81.8% for bHA with osteogenically differentiated MSC. For the control group, the remaining defect width measured 46.2% which was a statistically significant difference (p < 0.001).

Conclusions

The study design was suitable to evaluate tissue-engineered bone grafts prior to a clinical application. In this experimental set-up with the described maxillary defect, no promoting influence on bone formation of bone grafts containing bHA could be confirmed.

Clinical relevance

The creation of a sufficient tissue-engineered bone graft for alveolar cleft osteoplasty could preserve patients from donor site morbidity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Dixon MJ, Marazita ML, Beaty TH et al (2011) Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet 12(3):167–178. doi:10.1038/nrg2933

    Article  PubMed  PubMed Central  Google Scholar 

  2. Witsenburg B (1985) The reconstruction of anterior residual bone defects in patients with cleft lip, alveolus and palate. A review. J Maxillofac Surg 13(5):197–208

    Article  PubMed  Google Scholar 

  3. Horswell BB, Henderson JM (2003) Secondary osteoplasty of the alveolar cleft defect. J Oral Maxillofac Surg 61(9):1082–1090

    Article  PubMed  Google Scholar 

  4. Younger EM, Chapman MW (1989) Morbidity at bone graft donor sites. J Orthop Trauma 3(3):192–195

    Article  PubMed  Google Scholar 

  5. Moreau JL, Caccamese JF, Coletti DP et al (2007) Tissue engineering solutions for cleft palates. J Oral Maxillofac Surg 65(12):2503–2511. doi:10.1016/j.joms.2007.06.648

    Article  PubMed  Google Scholar 

  6. Nguyen PD, Lin CD, Allori AC et al (2009) Establishment of a critical-sized alveolar defect in the rat: a model for human gingivoperiosteoplasty. Plast Reconstr Surg 123(3):817–825. doi:10.1097/PRS.0b013e31819ba2f4

    Article  PubMed  Google Scholar 

  7. Draenert FG, Huetzen D, Neff A et al (2014) Vertical bone augmentation procedures: basics and techniques in dental implantology. J Biomed Mater Res A 102(5):1605–1613. doi:10.1002/jbm.a.34812

    Article  PubMed  Google Scholar 

  8. Herford AS, Nguyen K (2015) Complex bone augmentation in alveolar ridge defects. Oral Maxillofac Surg Clin North Am 27(2):227–244. doi:10.1016/j.coms.2015.01.003

    Article  PubMed  Google Scholar 

  9. Feinberg SE, Weisbrode SE, Heintschel G (1989) Radiographic and histological analysis of tooth eruption through calcium phosphate ceramics in the cat. Arch Oral Biol 34(12):975–984

    Article  PubMed  Google Scholar 

  10. Salgado AJ, Coutinho OP, Reis RL (2004) Bone tissue engineering: state of the art and future trends. Macromol Biosci 4(8):743–765. doi:10.1002/mabi.200400026

    Article  PubMed  Google Scholar 

  11. Fisher JN, Peretti GM, Scotti C (2016) Stem cells for bone regeneration: from cell-based therapies to decellularised engineered extracellular matrices. Stem Cells Int 2016:9352598. doi:10.1155/2016/9352598

    Article  PubMed  PubMed Central  Google Scholar 

  12. Yousefi A, James PF, Akbarzadeh R et al (2016) Prospect of stem cells in bone tissue engineering: a review. Stem Cells Int 2016:6180487. doi:10.1155/2016/6180487

    Article  PubMed  PubMed Central  Google Scholar 

  13. Logeart-Avramoglou D, Anagnostou F, Bizios R et al (2005) Engineering bone: challenges and obstacles. J Cell Mol Med 9(1):72–84

    Article  PubMed  Google Scholar 

  14. Gladysz D, Hozyasz KK (2015) Stem cell regenerative therapy in alveolar cleft reconstruction. Arch Oral Biol 60(10):1517–1532. doi:10.1016/j.archoralbio.2015.07.003

    Article  PubMed  Google Scholar 

  15. Mastrangelo F, Quaresima R, Grilli A et al (2013) A comparison of bovine bone and hydroxyapatite scaffolds during initial bone regeneration: an in vitro evaluation. Implant Dent 22(6):613–622. doi:10.1097/ID.0b013e3182a69858

    Article  PubMed  Google Scholar 

  16. Santos PL, Gulinelli JL, Telles CS et al (2013) Bone substitutes for peri-implant defects of postextraction implants. Int J Biomater 2013:307136. doi:10.1155/2013/307136

    Article  PubMed  PubMed Central  Google Scholar 

  17. Oliveira R, El HM, Carrel JP et al (2012) Rehabilitation of the edentulous posterior maxilla after sinus floor elevation using deproteinized bovine bone: a 9-year clinical study. Implant Dent 21(5):422–426. doi:10.1097/ID.0b013e3182691873

    Article  PubMed  Google Scholar 

  18. Kato E, Lemler J, Sakurai K et al (2014) Biodegradation property of beta-tricalcium phosphate-collagen composite in accordance with bone formation: a comparative study with Bio-Oss Collagen(R) in a rat critical-size defect model. Clin Implant Dent Relat Res 16(2):202–211. doi:10.1111/j.1708-8208.2012.00467.x

    Article  PubMed  Google Scholar 

  19. Lammers L, Naujoks C, Berr K et al (2012) Impact of DAG stimulation on mineral synthesis, mineral structure and osteogenic differentiation of human cord blood stem cells. Stem Cell Res 8(2):193–205. doi:10.1016/j.scr.2011.09.004

    Article  PubMed  Google Scholar 

  20. Kunert-Keil C, Scholz F, Gedrange T et al (2015) Comparative study of biphasic calcium phosphate with beta-tricalcium phosphate in rat cranial defects—a molecular-biological and histological study. Ann Anat 199:79–84. doi:10.1016/j.aanat.2013.12.001

    Article  PubMed  Google Scholar 

  21. Korn P, Schulz MC, Range U et al (2014) Efficacy of tissue engineered bone grafts containing mesenchymal stromal cells for cleft alveolar osteoplasty in a rat model. J Craniomaxillofac Surg 42(7):1277–1285. doi:10.1016/j.jcms.2014.03.010

    Article  PubMed  Google Scholar 

  22. Donath K, Breuner G (1982) A method for the study of undecalcified bones and teeth with attached soft tissues. The Sage-Schliff (sawing and grinding) technique. J Oral Pathol 11(4):318–326

    Article  PubMed  Google Scholar 

  23. Pradel W, Lauer G (2012) Tissue-engineered bone grafts for osteoplasty in patients with cleft alveolus. Ann Anat 194(6):545–548. doi:10.1016/j.aanat.2012.06.002

    Article  PubMed  Google Scholar 

  24. Mehrara BJ, Saadeh PB, Steinbrech DS et al (2000) A rat model of gingivoperiosteoplasty. J Craniofac Surg 11(1):54–58

    Article  PubMed  Google Scholar 

  25. Mostafa NZ, Doschak MR, Major PW et al (2014) Reliable critical sized defect rodent model for cleft palate research. J Craniomaxillofac Surg 42(8):1840–1846. doi:10.1016/j.jcms.2014.07.001

    Article  PubMed  Google Scholar 

  26. Pourebrahim N, Hashemibeni B, Shahnaseri S et al (2013) A comparison of tissue-engineered bone from adipose-derived stem cell with autogenous bone repair in maxillary alveolar cleft model in dogs. Int J Oral Maxillofac Surg 42(5):562–568. doi:10.1016/j.ijom.2012.10.012

    Article  PubMed  Google Scholar 

  27. Zhang J, Yang R, Liu Z et al (2015) Loss of lysyl oxidase-like 3 causes cleft palate and spinal deformity in mice. Hum Mol Genet 24(21):6174–6185. doi:10.1093/hmg/ddv333

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yamada M, Yamamoto N, Ohgami S et al (2014) The effect of sevoflurane on developing A/J strain mouse embryos using a whole-embryo culture system—the incidence of cleft lip in culture embryos. Vitro Cell Dev Biol Anim 50(3):237–242. doi:10.1007/s11626-013-9697-y

    Article  Google Scholar 

  29. Harris CT, Cooper LF (2004) Comparison of bone graft matrices for human mesenchymal stem cell-directed osteogenesis. J Biomed Mater Res A 68(4):747–755. doi:10.1002/jbm.a.20107

    Article  PubMed  Google Scholar 

  30. Lohberger B, Payer M, Rinner B et al (2012) Human intraoral harvested mesenchymal stem cells: characterization, multilineage differentiation analysis, and 3-dimensional migration of natural bone mineral and tricalcium phosphate scaffolds. J Oral Maxillofac Surg 70(10):2309–2315. doi:10.1016/j.joms.2011.06.216

    Article  PubMed  Google Scholar 

  31. Liu Q, Douglas T, Zamponi C et al (2011) Comparison of in vitro biocompatibility of NanoBone((R)) and BioOss((R)) for human osteoblasts. Clin Oral Implants Res 22(11):1259–1264. doi:10.1111/j.1600-0501.2010.02100.x

    Article  PubMed  Google Scholar 

  32. Carmagnola D, Adriaens P, Berglundh T (2003) Healing of human extraction sockets filled with Bio-Oss. Clin Oral Implants Res 14(2):137–143

    Article  PubMed  Google Scholar 

  33. Esposito M, Grusovin MG, Coulthard P et al (2006) The efficacy of various bone augmentation procedures for dental implants: a Cochrane systematic review of randomized controlled clinical trials. Int J Oral Maxillofac Implants 21(5):696–710

    PubMed  Google Scholar 

  34. Mangano C, Scarano A, Perrotti V et al (2007) Maxillary sinus augmentation with a porous synthetic hydroxyapatite and bovine-derived hydroxyapatite: a comparative clinical and histologic study. Int J Oral Maxillofac Implants 22(6):980–986

    PubMed  Google Scholar 

  35. Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147

    Article  PubMed  Google Scholar 

  36. Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone. Biology and clinical applications. J Bone Joint Surg Am 84-A(6):1032–1044

    Article  PubMed  Google Scholar 

  37. Komori T (2003) Requisite roles of Runx2 and Cbfb in skeletal development. J Bone Miner Metab 21(4):193–197. doi:10.1007/s00774-002-0408-0

    PubMed  Google Scholar 

  38. Pratap J, Galindo M, Zaidi SK et al (2003) Cell growth regulatory role of Runx2 during proliferative expansion of preosteoblasts. Cancer Res 63(17):5357–5362

    PubMed  Google Scholar 

  39. Jonason JH, Xiao G, Zhang M et al (2009) Post-translational regulation of Runx2 in bone and cartilage. J Dent Res 88(8):693–703. doi:10.1177/0022034509341629

    Article  PubMed  PubMed Central  Google Scholar 

  40. Jensen ED, Gopalakrishnan R, Westendorf JJ (2010) Regulation of gene expression in osteoblasts. Biofactors 36(1):25–32. doi:10.1002/biof.72

    PubMed  PubMed Central  Google Scholar 

  41. Ducy P (2000) Cbfa1: a molecular switch in osteoblast biology. Dev Dyn 219(4):461–471. doi:10.1002/1097-0177(2000)9999:9999<:AID-DVDY1074>3.0.CO;2-C

    Article  PubMed  Google Scholar 

  42. Komori T, Yagi H, Nomura S et al (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89(5):755–764

    Article  PubMed  Google Scholar 

  43. Mostafa NZ, Talwar R, Shahin M et al (2015) Cleft palate reconstruction using collagen and nanofiber scaffold incorporating bone morphogenetic protein in rats. Tissue Eng Part A 21(1–2):85–95. doi:10.1089/ten.tea.2014.0075

    Article  PubMed  Google Scholar 

  44. Mayer M, Hollinger J, Ron E et al (1996) Maxillary alveolar cleft repair in dogs using recombinant human bone morphogenetic protein-2 and a polymer carrier. Plast Reconstr Surg 98(2):247–259

    Article  PubMed  Google Scholar 

  45. Nguyen PD, Lin CD, Allori AC et al (2009) Scaffold-based rhBMP-2 therapy in a rat alveolar defect model: implications for human gingivoperiosteoplasty. Plast Reconstr Surg 124(6):1829–1839. doi:10.1097/PRS.0b013e3181bf8024

    Article  PubMed  Google Scholar 

  46. Araujo M, Linder E, Lindhe J (2009) Effect of a xenograft on early bone formation in extraction sockets: an experimental study in dog. Clin Oral Implants Res 20(1):1–6. doi:10.1111/j.1600-0501.2008.01606.x

    Article  PubMed  Google Scholar 

  47. van Hout WMMT, van der Molen M, Aebele B, Breugem CC et al (2011) Reconstruction of the alveolar cleft: can growth factor-aided tissue engineering replace autologous bone grafting? A literature review and systematic review of results obtained with bone morphogenetic protein-2. Clin Oral Investig 15(3):297–303. doi:10.1007/s00784-011-0547-6

    Article  PubMed  PubMed Central  Google Scholar 

  48. Herford AS, Boyne PJ, Rawson R et al (2007) Bone morphogenetic protein-induced repair of the premaxillary cleft. J Oral Maxillofac Surg 65(11):2136–2141. doi:10.1016/j.joms.2007.06.670

    Article  PubMed  Google Scholar 

  49. Dickinson BP, Ashley RK, Wasson KL et al (2008) Reduced morbidity and improved healing with bone morphogenic protein-2 in older patients with alveolar cleft defects. Plast Reconstr Surg 121(1):209–217. doi:10.1097/01.prs.0000293870.64781.12

    Article  PubMed  Google Scholar 

  50. Alonso N, Tanikawa DY, Freitas RS et al (2010) Evaluation of maxillary alveolar reconstruction using a resorbable collagen sponge with recombinant human bone morphogenetic protein-2 in cleft lip and palate patients. Tissue Eng Part C Methods 16(5):1183–1189. doi:10.1089/ten.TEC.2009.0824

    Article  PubMed  Google Scholar 

  51. Benlidayi ME, Tatli U, Kurkcu M et al (2012) Comparison of bovine-derived hydroxyapatite and autogenous bone for secondary alveolar bone grafting in patients with alveolar clefts. J Oral Maxillofac Surg 70(1):e95–e102. doi:10.1016/j.joms.2011.08.041

    Article  PubMed  Google Scholar 

  52. Behnia H, Khojasteh A, Kiani MT et al (2013) Bone regeneration with a combination of nanocrystalline hydroxyapatite silica gel, platelet-rich growth factor, and mesenchymal stem cells: a histologic study in rabbit calvaria. Oral Surg Oral Med Oral Pathol Oral Radiol 115(2):e7–15. doi:10.1016/j.oooo.2011.09.034

    Article  PubMed  Google Scholar 

  53. Berger M, Probst F, Schwartz C et al (2015) A concept for scaffold-based tissue engineering in alveolar cleft osteoplasty. J Craniomaxillofac Surg 43(6):830–836. doi:10.1016/j.jcms.2015.04.023

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors want to thank Mrs. Diana Jünger for her extensive assistance in preparing the bone grafts. Furthermore, the authors are grateful to Dr. Roland Jung and the team of the Experimental Centre of the Medical Faculty “Carl Gustav Carus”, Technische Universität Dresden, for the care of the animals and assistance during the surgical interventions. Dr. Heike Meißner is acknowledged for the scanning electron microscope images. Moreover, the authors thank Mr. Torsten Jannasch for the assistance in preparing the images.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Paula Korn.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

The study was financially supported by an internal research grant “MeDDrive Projekt Start” of the Faculty of Medicine “Carl Gustav Carus”, Technische Universität Dresden, Germany. The bone substitute was kindly provided by Geistlich Biomaterials, Wolhusen, Switzerland.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. All applicable international, national and/or institutional guidelines for the care and use of animals were followed.

Informed consent

For this type of study, formal consent is not required.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Korn, P., Hauptstock, M., Range, U. et al. Application of tissue-engineered bone grafts for alveolar cleft osteoplasty in a rodent model. Clin Oral Invest 21, 2521–2534 (2017). https://doi.org/10.1007/s00784-017-2050-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-017-2050-1

Keywords

Navigation