Bone is a highly responsive organ, which continuously adapts to the environment it is subjected to in order to withstand metabolic demands. These events are difficult to study in this particular tissue in vivo, due to its rigid, mineralised structure and inaccessibility of the cellular component located within. This manuscript presents the development of a micron-scale bone organoid prototype, a concept that can allow the study of bone processes at the cell-tissue interface. The model is constructed with a combination of primary female osteoblastic and osteoclastic cells, seeded onto femoral head micro-trabeculae, where they recapitulate relevant phenotypes and functions. Subsequently, constructs are inserted into a simulated microgravity bioreactor (NASA-Synthecon) to model a pathological state of reduced mechanical stimulation. In these constructs, we detected osteoclastic bone resorption sites, which were different in morphology in the simulated microgravity group compared to static controls. Once encapsulated in human fibrin and exposed to analogue microgravity for 5 days, masses of bone can be observed being lost from the initial structure, allowing to simulate the bone loss process further. Constructs can function as multicellular, organotypic units. Large osteocytic projections and tubular structures develop from the initial construct into the matrix at the millimetre scale. Micron-level fragments from the initial bone structure are detected travelling along these tubules and carried to sites distant from the native structure, where new matrix formation is initiated. We believe this model allows the study of fine-level physiological processes, which can shed light into pathological bone loss and imbalances in bone remodelling.

骨骼是一个高度敏感的器官，它不断适应其所处的环境，以承受代谢需求。由于这种特定组织的刚性、矿化结构以及内部细胞成分的不可接近性，这些事件很难在体内研究。该手稿介绍了微米级骨类器官原型的开发，这一概念可以研究细胞-组织界面的骨过程。该模型由原代雌性成骨细胞和破骨细胞组合构建，接种到股骨头微小梁上，在那里它们重演相关的表型和功能。随后，将构建体插入模拟微重力生物反应器（NASA-Synthecon）中，以模拟机械刺激减少的病理状态。在这些结构中，我们检测到破骨细胞骨吸收位点，与静态对照组相比，模拟微重力组的形态有所不同。一旦封装在人体纤维蛋白中并暴露在模拟微重力下 5 天，就可以观察到大量骨从初始结构中丢失，从而可以进一步模拟骨丢失过程。构建体可以作为多细胞、器官型单位发挥作用。大的骨细胞突起和管状结构从最初的结构发展成毫米级的基质。检测到来自初始骨结构的微米级碎片沿着这些小管行进，并被带到远离天然结构的部位，在那里开始新的基质形成。我们相信该模型可以研究精细的生理过程，从而揭示病理性骨质流失和骨重塑的不平衡。