02251nas a2200301   4500000000100000000000100001008004100002260001500043653001900058653002800077653001100105653001200116653002600128653001100154653004100165653001600206653001900222653002900241100001200270700001400282700001300296700001100309245008400320300000900404490000700413520151500420022001401935       2023                            d  c2023-04-1010aBone and Bones10aCell Culture Techniques10aHumans10aHypoxia10aLab-On-A-Chip Devices10aOxygen10abone disease bone-on-a-chip platform10abone marrow10acell culturing10ahypoxic microenvironment1 aChen Li1 aRong Zhao1 aHui Yang1 aLi Ren00aConstruction of Bone Hypoxic Microenvironment Based on Bone-on-a-Chip Platforms  a69990 v243 aThe normal physiological activities and functions of bone cells cannot be separated from the balance of the oxygenation level, and the physiological activities of bone cells are different under different oxygenation levels. At present, in vitro cell cultures are generally performed in a normoxic environment, and the partial pressure of oxygen of a conventional incubator is generally set at 141 mmHg (18.6%, close to the 20.1% oxygen in ambient air). This value is higher than the mean value of the oxygen partial pressure in human bone tissue. Additionally, the further away from the endosteal sinusoids, the lower the oxygen content. It follows that the construction of a hypoxic microenvironment is the key point of in vitro experimental investigation. However, current methods of cellular research cannot realize precise control of oxygenation levels at the microscale, and the development of microfluidic platforms can overcome the inherent limitations of these methods. In addition to discussing the characteristics of the hypoxic microenvironment in bone tissue, this review will discuss various methods of constructing oxygen gradients in vitro and measuring oxygen tension from the microscale based on microfluidic technology. This integration of advantages and disadvantages to perfect the experimental study will help us to study the physiological responses of cells under more physiological-relevant conditions and provide a new strategy for future research on various in vitro cell biomedicines.  a1422-0067