Supplementary Data for Upload.xlsx from Stresses and strains on the human foetal skeleton during development

Mechanical forces generated by foetal kicks and movements result in stimulation of the foetal skeleton in the form of stress and strain. This stimulation is known to be critical for prenatal musculoskeletal development; indeed, abnormal or absent movements have been implicated in multiple congenital disorders. However, the mechanical stress and strain experienced by the developing human skeleton in utero have never before been characterized. Here, we quantify the biomechanics of foetal movements during the second half of gestation by modelling foetal movements captured using novel cine-MRI technology. By tracking these movements, quantifying foetal kick and muscle forces, and applying them to three-dimensional geometries of the foetal skeleton, we test the hypothesis that stress and strain change over ontogeny. We find that foetal kick force increases significantly from 20 to 30 weeks gestation, before decreasing towards term. However, stress and strain in the foetal skeleton rises significantly over the latter half of gestation. This increasing trend with gestational age is important because changes in foetal movement patterns in late pregnancy have been linked to poor foetal outcomes and musculoskeletal malformations. This research represents the first quantification of kick force and mechanical stress and strain due to foetal movements in the human skeleton in utero, thus advancing our understanding of the biomechanical environment of the uterus. Further, by revealing a potential link between foetal biomechanics and skeletal malformations, our work will stimulate future research in tissue engineering and mechanobiology.

胎儿踢动与肢体活动所产生的机械力，会以应力（stress）与应变（strain）的形式对胎儿骨骼产生刺激作用。已知此类刺激对产前肌肉骨骼发育至关重要；事实上，运动异常或运动缺失已被证实与多种先天性疾病相关。然而，迄今为止尚未有研究对宫内发育中的人类骨骼所承受的机械应力与应变进行过系统性表征。本研究借助新型电影磁共振成像（cine-MRI）技术捕获胎儿活动，并通过建模手段量化妊娠后半阶段胎儿活动的生物力学特性。通过追踪此类活动、量化胎儿踢动力与肌肉力，并将其应用于胎儿骨骼的三维几何模型中，我们验证了“应力与应变随个体发育（ontogeny）发生变化”这一假说。研究发现，胎儿踢动力在妊娠20至30周时显著升高，随后逐渐下降至足月妊娠阶段。但胎儿骨骼所承受的应力与应变，在妊娠后半阶段呈现显著上升趋势。这种随胎龄增长的上升趋势具有重要意义，因为妊娠晚期胎儿活动模式的改变，已被证实与不良胎儿结局及肌肉骨骼畸形相关。本研究首次实现了宫内胎儿活动对人类骨骼产生的踢动力与机械应力、应变的量化分析，从而加深了我们对子宫内生物力学环境的认知。此外，本研究揭示了胎儿生物力学与骨骼畸形之间的潜在关联，将为组织工程与力学生物学领域的未来研究注入新动力。