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Development of a micropatterned platform for studying mechanobioloy of osteoblast-osteocyte interactions in reduced gravity space conditions Authors: C. Yvanoff, G. Garbenciute, V. Navikas, M. Perez Gonzalez, H. Sahli, R. Valiokas, G. Dietler, S. Kasas and R. Willaert Publication Date: Jul. 2019
Abstract: Purpose of work Bone tissue homeostasis relies on the balanced activities of two cell types: the bone-forming osteoblasts and the bone-degrading osteoclasts. This equilibrium is ensured by the last bone cell type, namely the osteocyte. Over the past 30 years, it has been extensively reported that bone cells are sensitive and responsive to mechanical stimulation. More precisely, mechanical cues promote bone strength whereas the lack of physical stimuli results in significant bone loss. Hence, routine physical exercise is strongly recommended to maintain healthy bones. Nevertheless, astronauts exposed to microgravity, lose bone tissue at an accelerated rate despite intense physical training during their flight. Therefore, gravity is itself an important factor influencing bone cell mechanobiology. However, the exact mechanisms through which bone cells perceive, translate and respond to microgravity, are still poorly understood. In consequences, long-term exposure to space conditions is not yet a livable option. Our approach and resultsOur research aims at contributing to the understanding of the molecular basis underlying bone cell mechanobiology in reduced gravity conditions. Specifically, we focus on developing a platform which will allow us to study the cooperative answer of bone cells. Indeed, although the mechanobiology of each bone cell type has been investigated separately, there is still need for studies analyzing the communication between the different bone cells under reduced gravity. To do so, we are using micro- and nanoscale technologies, such as cell micropatterning, robotic printing and microfluidics, to develop a “bone-on-a-chip”. Cell micropatterning enables to direct the adherence and growth of cells according to specific spatial cues. We used this technology to generate physiological-like networks of interacting bone cells (osteoblasts and osteocytes). On the other hand, robotic printing enables to dispense nanoliter droplets of cell suspensions at specific locations with micrometer accuracy. Hence, we optimized the printing of osteoblasts and osteocytes on their micropatterned areas by means of a non-contact cell printer (iTWO녘, M2 Automation). After printing the cells onto the micropatterned chip, the platform is finalized by covering it with the top of a microfluidic channel, which enables long-term culture. SignificanceLunar conditions will affect bone cell physiology. These alterations may have important consequences for humans on the moon and future space flights. Additionally, cellular mechanosensation is critical in bone diseases responsible for enormous human suffering such as osteoporosis, and reduced gravity research could contribute significantly to find a cure for these diseases.
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