Publikationsdatenbank

Comparative cephalometric studies of the mandible in growing Göttingen Minipigs using 3D Computed Tomography: Refining experimental dental and orofacial research (2020)

Art

Hochschulschrift

Autor

Corte, Giuliano (WE 1)

Quelle

Berlin: Mensch & Buch Verlag, 2020 — 141 Seiten

Sprache

Englisch

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/26363

Kontakt

Institut für Veterinär-Anatomie

Koserstr. 20
14195 Berlin
+49 30 838 75784
anatomie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

This thesis was created as a subproject of the Berlin-Brandenburg Research Platform, with the integrated graduate school "Innovations in the 3R Research - Genetic Engineering, Tissue Engineering and Bioinformatics". BB3R was established under the umbrella of the Dahlem Research School (DRS) of Freie Universität Berlin and aims to provide substantial progress in 3R alternatives by intensive systematic research. The overarching objective of this thesis was to establish an anatomical data collection with detailed and age-related data of the mandible and the mandibular canal of growing Göttingen Minipigs using 3D Computed Tomography and to compare this data with human mandibular anatomy. Therefore, it could be determined, whether the Göttingen Minipig represents an anatomically suitable animal model for orofacial surgery. In order to refine and avoid intra- and postoperative complications in the sense of the 3Rs, this data collection should be prospectively used in dental and orofacial experiments. Chapter 1 generally introduces the market size, sales figures and the utilization of dental implants in dentistry and orofacial reconstructive surgery. It also focusses on the required preclinical testing procedures to proof the implants’ biocompatibility and safety in order to be authorized for clinical testing in humans. This involves in vivo testing in large animal models. Due to stricter legal requirements over the use of primates for scientific purposes, the Göttingen Minipig is nowadays extensively used as animal model in pre-clinical dental and orofacial research. Nevertheless, several authors have raised concerns over the use of the Göttingen Minipig in this research area, observing complications and success rates below 60%. Chapter 2 gives a literature review about the development of different minipig breeds, their general scientific use and the corresponding German and European animal research numbers. Then the reader is introduced to the role of the Göttingen Minipig in dental and orofacial research, how the in vivo procedures are performed and what complications can occur. In addition, the European law, the definitions of the 3Rs and their implementation in research are elucidated. At the end of the chapter, the technical methodologies (CT, 2D and 3D reconstruction, Cephalometry and visualization software) used in this study, are explained. Chapter 3 lists the detailed objectives of the thesis. Chapter 4 covers the publication “Refining experimental dental implant testing in the Göttingen Minipig using 3D computed tomography – A morphometric study of the mandibular canal”. In this study, morphometric and age-related data of the mandibular canal and the alveolar ridge of the Göttingen Minipig was reported and compared with the human anatomy, in order to avoid complications during in vivo testing of endosseous dental implants. Using 3D computed tomography, six parameters of the mandibular canal as well as the alveolar bone height and the alveolar ridge width were measured in Göttingen Minipigs aged 12, 17 and 21 months. The study found that the volume, length and depth of the mandibular canal all increased with age. The width of the canal did not change significantly with age. There were high individual differences within each age group, for example within the 21 months old group the animal with the lowest canal volume of 4.7ml was 14kg heavier than the animal with the significantly highest volume of 13.4ml. In contrast to humans, minipigs possess a significantly larger mandibular canal. With higher age and increasing canal volume, loss of deep spongy bone in the posterior premolar and molar regions could be observed, which potentially results in the inferior alveolar neurovascular bundle coming into close proximity with the tooth roots. This reduced the available space for dental implants and could negatively affect implant stability and the integrity of the inferior alveolar neurovascular bundle. This problem is aggravated by the minipigs’ narrower alveolar ridge width in comparison with healthy humans. Surprisingly, the body mass does not have an influence on any of the measured parameters. When one images the inferior alveolar vein, two basic patterns occur. One being a straight traverse, the other being a variable undulating route where it rises and falls as it travels through the length of the canal. Dynamic anatomical changes could be proven until the age of 21 months. Due to ongoing growth it is inadvisable to use minipigs younger than 21 months in experimental implant dentistry. Paradoxically, the measurements of the 12 months old pigs indicate a closer alignment of their mandibular anatomy to that of humans, suggesting that they may be better models for implant studies. Given the variability in mandibular canal dimensions in similar age cohorts, the use of imaging techniques is essential for the selection of individual minipigs for the interventions and thus higher success rates. Chapter 5 covers the publication “Cephalometric studies of the mandible, its masticatory muscles and vasculature of growing Göttingen Minipigs – A comparative anatomical study to refine experimental mandibular surgery”. This study elucidated how comparable the mandible of Göttingen Minipigs and humans are, and whether the frequently reported complications could be caused by specific anatomical characteristics of the minipigs’ mandible, its masticatory muscles and associated vasculature. Therefore, twenty-two mandibular cephalometric parameters were measured on CT scans of Göttingen Minipigs aged between 12 and 21 months. Of the 22 parameters measured, only four were found to be highly comparable, whilst the others were not. Again, especially younger minipigs showed a closer alignment to human anatomy. Minipigs generally showed a higher mandibular ramus, anterior mentum height and a significantly longer mandible with a much steeper mandibular angle. They in contrast possess a shorter superior ramus length and a lower coronoid process volume. The 3D examinations of the minipigs’ vasculature pictured a large, tortuous network medial to the mandibular ramus, mainly consisting of the very prominent deep facial vein and maxillary artery. This vascular complex interferes with the principal sectional plane for MDO that could cause strong and inaccessible bleeding. The morphology and dimensions of the mandibular body in humans and minipigs are very different. Whilst humans have a mandibular body with an ovoid cross-section, that of minipigs can be pear-shaped. Consequently, bicortical screws that are positioned in the inferior part of the mandibular body as routinely performed in humans, could, when placed in a similar way in a Göttingen Minipig, cause trauma to the inferior alveolar nerves and vessels. Bicortical screws implanted in the inferior cortex would probably have impaired stability, due to the thin inferior bone thickness. Literature revealed that the dynamics of mastication in pigs and in humans differ greatly. Pigs have a higher crushing force and closing velocity than humans. In addition, they postoperatively grind their teeth extensively as well as bite on hard objects such as their cages that could potentially impair wound healing and implant stability. Based on the results of this study, the authors consider the Göttingen Minipig not to be an anatomically ideal animal model for experimental mandibular surgery research. The minipig mandible not only differs greatly from that of humans but also is highly variable in its morphology within animals of the same age group. This raises concerns, that extrapolating acquired scientific results of Göttingen Minipigs to humans could be misleading or incorrect. Due to the lack of alternative large animal models, the authors recommend to precisely plan mandibular surgical experiments based on radiographic techniques, such as Computed Tomography, and to choose suitable age groups and use customized implants based on the mandibular dimensions as reported in this study. Chapter 6 more precisely discusses the suitability of Göttingen Minipigs as an animal model for dental and orofacial research. In addition, alternative animal models for the Göttingen Minipigs, with their anatomical and physiological advantages and disadvantages are, in regards to the recommendations of the ISO 7405:2018, discussed. The chapter ends with conclusive remarks, while giving an outlook on a database planned in the future.