A new standardized critical size bone defect model in the pig forehead for comparative testing of bone regeneration materials
- 3 Downloads
The preclinical study aimed to establish a standardized preclinical model to investigate osseous graft consolidation in defect configurations of limited regenerative capacity.
Material and methods
Critical size defects (CSD) were prepared and titanium tubes inserted for defect separation from local bone in the forehead area of 18 pigs. Defects were filled with demineralized bovine bone mineral (DBBM) or served as empty controls and were covered with a resorbable collagen membrane (CM) or left untreated. Six randomly selected pigs were sacrificed after 4, 8 and 12 weeks. Specimens were histologically and histomorphometrically analysed focusing on newly formed bone (NFB), demineralized bovine bone mineral (DBBM) and soft tissue (ST) proportions.
Four weeks after defect preparation, no statistically significant difference concerning NFB quantity could be detected within the groups. Defects covered with the CM showed lower amounts of DBBM. After 6 and 12 weeks, defects augmented with DBBM in combination with a CM (8 weeks: 43.12 ± 4.31; 12 weeks: 43.05 ± 3.01) showed a statistically significant higher NFB rate compared to empty control defects covered with 8 weeks: 7.66 ± 0.59; 12 weeks or without a CM; 8 weeks: 8.62 ± 2.66; 12 weeks: 18.40 ± 2.40. CM application showed no significant impact on osseous defect regeneration or soft tissue formation. Superior NFB could be detected for basal aspect for several evaluation time points.
The modification of CSD with titanium tubes represents a suitable model to imitate a one-wall defect regeneration situation.
The established model represents a promising method to evaluate graft consolidation in one-wall defect configuration.
KeywordsCritical size defect Bone substitutes Demineralized bovine bone mineral Animal model
The study was undertaken in cooperation with the Semmelweis-University, Budapest, Hungary. Animal care keeping and surgical procedures were performed in the laboratories of the Semmelweis-University, Budapest, Hungary. Specimen processing was done in the laboratories of the Department of Oral and Maxillofacial Surgery, University of Erlangen-Nürnberg, Erlangen, Germany. Geistlich Pharma AG, Wolhusen, Switzerland, supported this study. The authors have no conflicts of interest. The work of Dr. E. Felszeghy, A. Krautheim-Zenk and S. Schönherr is highly appreciated.
The work was supported by Geistlich Pharma AG, Wolhusen, Switzerland (KC 354-12036).
Compliance with ethical standards
Conflict of interest
Tobias Moest declares that he has no conflict of interest. Karl Andreas Schlegel declares that he has no conflict of interest. Marco Kesting declares that he has no conflict of interest. Matthias Fenner declares that he has no conflict of interest. Rainer Lutz declares that he has no conflict of interest. Daniele Machado Beck declares that she has no conflict of interest. Cornelius von Wilmowsky declares that he has no conflict of interest.
The presented work was approved by the Pest county government department for food safety and animal health, Hungary (approval number: 1112/000/2003).
For this type of study, formal consent is not required.
- 1.Esposito M, Grusovin MG, Felice P, Karatzopoulos G, Worthington HV, Coulthard P (2009) Interventions for replacing missing teeth: horizontal and vertical bone augmentation techniques for dental implant treatment. Cochrane Database Syst Rev 4:CD003607. https://doi.org/10.1002/14651858.CD003607.pub4 Google Scholar
- 5.Schlegel KA, Lang FJ, Donath K, Kulow JT, Wiltfang J (2006) The monocortical critical size bone defect as an alternative experimental model in testing bone substitute materials. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102(1):7–13. https://doi.org/10.1016/j.tripleo.2005.09.011 CrossRefGoogle Scholar
- 7.Schlegel KA, Rupprecht S, Petrovic L, Honert C, Srour S, von Wilmowsky C, Felszegy E, Nkenke E, Lutz R (2009) Preclinical animal model for de novo bone formation in human maxillary sinus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 108(3):e37–e44. https://doi.org/10.1016/j.tripleo.2009.05.037 CrossRefGoogle Scholar
- 8.von Wilmowsky C, Moest T, Nkenke E, Stelzle F, Schlegel KA (2014) Implants in bone: part II. Research on implant osseointegration: material testing, mechanical testing, imaging and histoanalytical methods. Oral Maxillofac Surg 18(4):355–372. https://doi.org/10.1007/s10006-013-0397-2 CrossRefGoogle Scholar
- 9.Schmitz JP, Hollinger JO (1986) The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res (205):299–308Google Scholar
- 10.Sirola K (1960) Regeneration of defects in the calvaria. An experimental study. Ann Med Exp Biol Fenn 38(Suppl 2):1–87Google Scholar
- 15.Moest T, Wehrhan F, Lutz R, Schmitt CM, Neukam FW, Schlegel KA (2015) Extra-oral defect augmentation using autologous, bovine and equine bone blocks: a preclinical histomorphometrical comparative study. J Craniomaxillofac Surg 43(4):559–566. https://doi.org/10.1016/j.jcms.2015.02.012 CrossRefGoogle Scholar
- 18.Stockmann P, Park J, von Wilmowsky C, Nkenke E, Felszeghy E, Dehner JF, Schmitt C, Tudor C, Schlegel KA (2012) Guided bone regeneration in pig calvarial bone defects using autologous mesenchymal stem/progenitor cells - a comparison of different tissue sources. J Craniomaxillofac Surg 40(4):310–320. https://doi.org/10.1016/j.jcms.2011.05.004 CrossRefGoogle Scholar
- 19.Tudor C, Srour S, Thorwarth M, Stockmann P, Neukam FW, Nkenke E, Schlegel KA, Felszeghy E (2008) Bone regeneration in osseous defects-application of particulated human and bovine materials. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105(4):430–436. https://doi.org/10.1016/j.tripleo.2007.07.037 CrossRefGoogle Scholar
- 20.Schlegel KA, Kloss FR, Kessler P, Schultze-Mosgau S, Nkenke E, Wiltfang J (2003) Bone conditioning to enhance implant osseointegration: an experimental study in pigs. Int J Oral Maxillofac Implants 18(4):505–511Google Scholar
- 21.Jensen J, Tvedesøe C, Rölfing JH, Foldager CB, Lysdahl H, Kraft DC, Chen M, Baas J, Le DQ, Bünger CE (2016) Dental pulp-derived stromal cells exhibit a higher osteogenic potency than bone marrow-derived stromal cells in vitro and in a porcine critical-size bone defect model. SICOT J 20(2):16. https://doi.org/10.1051/sicotj/2016004 CrossRefGoogle Scholar
- 22.Taga ML, Granjeiro JM, Cestari TM, Taga R (2008) Healing of critical-size cranial defects in Guinea pigs using a bovine bone-derived resorbable membrane. Int J Oral Maxillofac Implants 23(3):427–436Google Scholar
- 23.Eitel F, Seiler H, Schweiberer L (1981) Morphologic examination of animal-experiment results: comparison with regeneration of the human bone-structure. I. Research methods (author's transl). Unfallheilkunde 84(6):250–254Google Scholar
- 26.Busenlechner D, Tangl S, Mair B, Fugger G, Gruber R, Redl H, Watzek G (2008) Simultaneous in vivo comparison of bone substitutes in a guided bone regeneration model. Biomaterials 29(22):3195–3200. https://doi.org/10.1016/j.biomaterials.2008.04.021 CrossRefGoogle Scholar
- 27.Zhu SJ, Choi BH, Huh JY, Jung JH, Kim BY, Lee SH (2006) A comparative qualitative histological analysis of tissue-engineered bone using bone marrow mesenchymal stem cells, alveolar bone cells, and periosteal cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101(2):164–169. https://doi.org/10.1016/j.tripleo.2005.04.006 CrossRefGoogle Scholar
- 30.Rothamel D, Schwarz F, Herten M, Ferrari D, Mischkowski RA, Sager M, Becker J (2009) Vertical ridge augmentation using xenogenous bone blocks: a histomorphometric study in dogs. Int J Oral Maxillofac Implants 24(2):243–250Google Scholar