Zhong Jingxiao, Shibata Yo, Wu Chi, Watanabe Chie, Chen Junning, Zheng Keke, Hu Jingrui, Swain Michael V, Li Qing
School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, Sydney, NSW 2006, Australia.
Department of Biomaterials and Engineering, Showa University School of Dentistry, Tokyo, Japan.
Acta Biomater. 2023 Oct 15;170:240-249. doi: 10.1016/j.actbio.2023.08.047. Epub 2023 Aug 25.
The bone-periodontal ligament-tooth (BPT) complex is a unique mechanosensing soft-/hard-tissue interface, which governs the most rapid bony homeostasis in the body responding to external loadings. While the correlation between such loading and alveolar bone remodelling has been widely recognised, it has remained challenging to investigate the transmitted mechanobiological stimuli across such embedded soft-/hard-tissue interfaces of the BPT complex. Here, we propose a framework combining three distinct bioengineering techniques (i, ii, and iii below) to elucidate the innate functional non-uniformity of the PDL in tuning mechanical stimuli to the surrounding alveolar bone. The biphasic PDL mechanical properties measured via nanoindentation, namely the elastic moduli of fibres and ground substance at the sub-tissue level (i), were used as the input parameters in an image-based constitutive modelling framework for finite element simulation (ii). In tandem with U-net deep learning, the Gaussian mixture method enabled the comparison of 5195 possible pseudo-microstructures versus the innate non-uniformity of the PDL (iii). We found that the balance between hydrostatic pressure in PDL and the strain energy in the alveolar bone was maintained within a specific physiological range. The innate PDL microstructure ensures the transduction of favourable mechanobiological stimuli, thereby governing alveolar bone homeostasis. Our outcomes expand current knowledge of the PDL's mechanobiological roles and the proposed framework can be adopted to a broad range of similar soft-/hard- tissue interfaces, which may impact future tissue engineering, regenerative medicine, and evaluating therapeutic strategies. STATEMENT OF SIGNIFICANCE: A combination of cutting-edge technologies, including dynamic nanomechanical testing, high-resolution image-based modelling and machine learning facilitated computing, was used to elucidate the association between the microstructural non-uniformity and biomechanical competence of periodontal ligaments (PDLs). The innate PDL fibre network regulates mechanobiological stimuli, which govern alveolar bone remodelling, in different tissues across the bone-PDL-tooth (BPT) interfaces. These mechanobiological stimuli within the BPT are tuned within a physiological range by the non-uniform microstructure of PDLs, ensuring functional tissue homeostasis. The proposed framework in this study is also applicable for investigating the structure-function relationship in broader types of fibrous soft-/hard- tissue interfaces.
骨-牙周膜-牙（BPT）复合体是一种独特的机械传感软/硬组织界面，它控制着身体中对外界负荷作出反应的最快速的骨内稳态。虽然这种负荷与牙槽骨重塑之间的相关性已得到广泛认可，但研究跨BPT复合体这种嵌入式软/硬组织界面传递的机械生物学刺激仍然具有挑战性。在此，我们提出一个结合三种不同生物工程技术（如下文的i、ii和iii）的框架，以阐明牙周膜在调节对周围牙槽骨的机械刺激方面固有的功能不均匀性。通过纳米压痕测量的双相牙周膜力学性能，即在亚组织水平的纤维和基质的弹性模量（i），被用作基于图像的本构建模框架中有限元模拟的输入参数（ii）。与U-net深度学习相结合，高斯混合方法能够将5195种可能的伪微观结构与牙周膜固有的不均匀性进行比较（iii）。我们发现，牙周膜中的静水压力与牙槽骨中的应变能之间的平衡在特定的生理范围内得以维持。牙周膜固有的微观结构确保了有利的机械生物学刺激的传导，从而控制牙槽骨内稳态。我们的研究结果扩展了当前对牙周膜机械生物学作用的认识，并且所提出的框架可应用于广泛的类似软/硬组织界面，这可能会影响未来的组织工程、再生医学以及评估治疗策略。重要性声明：结合了前沿技术，包括动态纳米力学测试、基于高分辨率图像的建模和机器学习辅助计算，用于阐明牙周膜（PDL）的微观结构不均匀性与生物力学能力之间的关联。牙周膜固有的纤维网络调节机械生物学刺激，这些刺激控制着跨骨-牙周膜-牙（BPT）界面的不同组织中的牙槽骨重塑。BPT内的这些机械生物学刺激通过牙周膜的不均匀微观结构在生理范围内进行调节，确保功能性组织内稳态。本研究中提出的框架也适用于研究更广泛类型的纤维软/硬组织界面中的结构-功能关系。
