Empa, Swiss Federal Laboratories for Materials Science and Technology, Thun, Switzerland.
Empa, Swiss Federal Laboratories for Materials Science and Technology, Thun, Switzerland.
J Mech Behav Biomed Mater. 2022 Oct;134:105405. doi: 10.1016/j.jmbbm.2022.105405. Epub 2022 Aug 1.
Preclinical studies often require animal models for in vivo experiments. Particularly in dental research, pig species are extensively used due to their anatomical similarity to humans. However, there is a considerable knowledge gap on the multiscale morphological and mechanical properties of the miniature pigs' jawbones, which is crucial for implant studies and a direct comparison to human tissue. In the present work, we demonstrate a multimodal framework to assess the jawbone quantity and quality for a minipig animal model that could be further extended to humans. Three minipig genotypes, commonly used in dental research, were examined: Yucatan, Göttingen, and Sinclair. Three animals per genotype were tested. Cortical bone samples were extracted from the premolar region of the mandible, opposite to the teeth growth. Global morphological, compositional, and mechanical properties were assessed using micro-computed tomography (micro-CT) together with Raman spectroscopy and nanoindentation measurements, averaged over the sample area. Local mineral-mechanical relationships were investigated with the site-matched Raman spectroscopy and micropillar compression tests. For this, a novel femtosecond laser ablation protocol was developed, allowing high-throughput micropillar fabrication and testing without exposure to high vacuum. At the global averaged sample level, bone relative mineralization demonstrated a significant difference between the genotypes, which was not observed from the complementary micro-CT measurements. Moreover, bone hardness measured by nanoindentation showed a positive trend with the relative mineralization. For all genotypes, significant differences between the relative mineralization and elastic properties were more pronounced within the osteonal regions of cortical bone. Site-matched micropillar compression and Raman spectroscopy highlighted the differences between the genotypes' yield stress and mineral to matrix ratios. The methods used at the global level (averaged over sample area) could be potentially correlated to the medical tools used to assess jawbone toughness and morphology in clinics. On the other hand, the local analysis methods can be applied to quantify compressive bone mechanical properties and their relationship to bone mineralization.
临床前研究通常需要动物模型进行体内实验。特别是在牙科研究中，由于猪种与人类在解剖学上具有相似性，因此被广泛应用。然而，对于小型猪颌骨的多尺度形态和力学性能，我们的了解还相当有限，而这些特性对于植入物研究以及与人类组织的直接比较至关重要。在本工作中，我们展示了一种多模态框架，用于评估小型猪动物模型的颌骨数量和质量，该框架可以进一步扩展到人类。我们检查了三种常用于牙科研究的小型猪基因型：尤卡坦猪、哥廷根猪和辛克莱猪。每种基因型测试了三只动物。皮质骨样本取自下颌前磨牙区域，与牙齿生长相对。使用微计算机断层扫描（micro-CT）结合拉曼光谱和纳米压痕测量，评估了样本区域的整体形态、组成和力学性能。通过与位点匹配的拉曼光谱和微柱压缩测试研究了局部矿物力学关系。为此，开发了一种新的飞秒激光烧蚀方案，允许在不暴露于高真空的情况下进行高通量微柱制造和测试。在全局平均样本水平上，基因型之间的骨相对矿化程度存在显著差异，而这一差异无法从互补的 micro-CT 测量中观察到。此外，纳米压痕测量的骨硬度与相对矿化程度呈正相关。对于所有基因型，皮质骨骨单位区域内的相对矿化程度与弹性特性之间的差异更为显著。与位点匹配的微柱压缩和拉曼光谱突出了基因型屈服应力和矿物质与基质比值的差异。在全局水平（样本面积平均）使用的方法可能与临床上用于评估颌骨韧性和形态的医疗工具相关。另一方面，局部分析方法可用于量化压缩骨力学性能及其与骨矿化的关系。
