Date Published: April 25, 2019
Publisher: Public Library of Science
Author(s): Giuliano Mario Corte, Hana Hünigen, Kenneth C. Richardson, Stefan M. Niehues, Johanna Plendl, Carlos Tomaz.
Over many decades, the Göttingen Minipig has been used as a large animal model in experimental surgical research of the mandible. Recently several authors have raised concerns over the use of the Göttingen Minipig in this research area, observing problems with post-operative wound healing and loosening implants. To reduce these complications during and after surgery and to improve animal welfare in mandibular surgery research, the present study elucidated how comparable the mandible of minipigs is to that of humans and whether these complications could be caused by specific anatomical characteristics of the minipigs’ mandible, its masticatory muscles and associated vasculature. Twenty-two mandibular cephalometric parameters were measured on CT scans of Göttingen Minipigs aged between 12 and 21 months. Ultimately, we compared this data with human data reported in the scientific literature. In addition, image segmentation was used to determine the masticatory muscle morphology and the configuration of the mandibular blood vessels. Compared to data of humans, significant differences in the mandibular anatomy of minipigs were found. Of the 22 parameters measured only four were found to be highly comparable, whilst the others were not. The 3D examinations of the minipigs vasculature showed a very prominent deep facial vein directly medial to the mandibular ramus and potentially interfering with the sectional plane of mandibular distraction osteogenesis. Damage to this vessel could result in inaccessible bleeding. The findings of this study suggest that Göttingen Minipigs are not ideal animal models for experimental mandibular surgery research. Nevertheless if these minipigs are used the authors recommend that radiographic techniques, such as computed tomography, be used in the specific planning procedures for the mandibular surgical experiments. In addition, it is advisable to choose suitable age groups and customize implants based on the mandibular dimensions reported in this study.
In experimental surgery, the use of the most common experimental animals worldwide i.e. mice, rats and hamsters, is limited due to their small body size. Consequently, large animal models that have closer comparability to human dimensions are needed . Over recent decades, the use of primates and dogs in research, has met with increasing societal resistance, mostly on ethical grounds. However, the pig has emerged as an acceptable alternative species because it is regarded by society as a production animal . Furthermore, many aspects of a pig’s physiology are similar to that of humans, making them especially suitable as large animal models for biomedical research [3–5]. Domestic pig breeds have a high adult body weight and large size that is frequently coupled with aggressive behaviour that have proven to be challenging in their husbandry [6, 7]. In 1949, the first miniature pigs namely, Minnesota minipigs, were bred to overcome these problems . Subsequently since its development in the 1960s, the Göttingen Minipig has become the most widely used pig breed and one of the smallest available for research . Its small size, low average adult body weight of around 35 kg and rapid growth allows easier handling and more economic housing than conventional domestic pig breeds. Furthermore, its early sexual maturity makes it more convenient for long-term studies than normal-sized pigs or other large animal models [10–13]. Because of that, the Göttingen Minipig has been used frequently in mandibular surgical research over recent decades [14, 15].
A computed tomographic study of Göttingen Minipigs approved by the Regional Office for Health and Social Affairs Berlin (permit IC113-G 0281/12) was conducted in 2007 and 2008 at the research facility for experimental surgery of the medical faculty (certified by ISO 9001) at Charité–Universitätsmedizin Berlin, Campus Virchow-Klinikum . These CT scans were re-used for the cephalometric measurements of the present study. Whilst this precluded an optimal study design, it promoted the 3Rs by eliminating additional animal experiments.
The mean values, standard deviations and p-values of all parameters measured are presented in Table 3. The p-values are the results of the statistical hypothesis tests conducted to determine if the parameter data of the three minipig age groups differ significantly from each other. Depending whether normal or non-normal distribution was present, student’s t- (Independent and Paired), Mann-Whitney-U-, Wilcoxon- or Kruskall-Wallis Test was utilized. The data of left and right hemimandibles did not show any significant differences and were therefore pooled. All parameters (Table 3) showed significant correlations between the left and right hemimandibles and therefore no significant asymmetries were observable.
In presurgical planning of human mandibular surgery and reconstruction, numerous cephalometric parameters are measured routinely. Because experimental approaches for these procedures are often developed in Göttingen Minipigs, we selected 22 of these parameters and measured them using CT scans of subadult and adult Göttingen Minipigs. By doing so, we evaluated the dimensions and the overall anatomical growth changes and ultimately compared these with human data from the literature. Of the 22 parameters measured only four were found to be highly comparable, whilst the others were not.
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 in fact requires carefully conducted presurgical planning using radiographic techniques, such as Computed Tomography. The minipig mandibular anatomy of younger animals (12m) is aligned more closely to that of humans. However, because of ongoing growth changes until the age of 21 months, only older Göttingen Minipigs should be used. The anatomical properties of mandible of the minipigs, i.e. the blood vessels medial to the ramus interfering with the sectional plane for MDO, can result in complications that are relevant to animal welfare and may additionally contribute negatively to their suitability.