Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
CÚRAM Center for Research in Medical Devices, National University of Ireland, Galway, Ireland.
Biofabrication. 2023 Jun 6;15(3). doi: 10.1088/1758-5090/acd6be.
Endochondral ossification (EO) is an essential biological process than underpins how human bones develop, grow, and heal in the event of a fracture. So much is unknown about this process, thus clinical manifestations of dysregulated EO cannot be adequately treated. This can be partially attributed to the absence of predictivemodels of musculoskeletal tissue development and healing, which are integral to the development and preclinical evaluation of novel therapeutics. Microphysiological systems, or organ-on-chip devices, are advancedmodels designed for improved biological relevance compared to traditionalculture models. Here we develop a microphysiological model of vascular invasion into developing/regenerating bone, thereby mimicking the process of EO. This is achieved by integrating endothelial cells and organoids mimicking different stages of endochondral bone development within a microfluidic chip. This microphysiological model is able to recreate key events in EO, such as the changing angiogenic profile of a maturing cartilage analogue, and vascular induced expression of the pluripotent transcription factors SOX2 and OCT4 in the cartilage analogue. This system represents an advancedplatform to further EO research, and may also serve as a modular unit to monitor drug responses on such processes as part of a multi-organ system.
软骨内骨化（endochondral ossification，EO）是一个基本的生物学过程，支撑着人类骨骼的发育、生长和在骨折时的愈合。这个过程有太多的未知之处，因此，调控异常的 EO 的临床表现不能得到充分的治疗。这在一定程度上是由于缺乏对骨骼肌肉组织发育和愈合的预测模型，而这些模型是新型治疗方法的开发和临床前评估的关键。微生理系统或器官芯片设备是一种先进的模型，与传统的培养模型相比，具有更高的生物学相关性。在这里，我们开发了一种血管侵入发育/再生骨的微生理模型，从而模拟了 EO 的过程。这是通过在微流控芯片中整合内皮细胞和模拟不同阶段软骨内骨发育的类器官来实现的。这种微生理模型能够重现 EO 中的关键事件，例如成熟软骨类似物中血管生成特征的变化，以及血管诱导软骨类似物中多能转录因子 SOX2 和 OCT4 的表达。该系统代表了 EO 研究的一个先进平台，也可以作为一个模块化单元，用于监测药物对多器官系统中此类过程的反应。
