Pressure-sensitive nutrient consumption via dynamic normal stress in rotational bioreactors

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• 作者：Laurence A. Belfiore ; Walter Bonani ; Matteo Leoni ; Carol J. Belfiore
• 关键词：Rotational bioreactor ; Nutrient consumption ; Diffusion equation ; Fick's second law ; Pressure-sensitive reactions ; Centrifugal force ; Normal stress ; Bone cell proliferation ; Pressure-sensitive Damkö ; hler number
• 刊名：Biophysical Chemistry
• 出版年：2009
• 出版时间：March 2009
• 年：2009
• 卷：140
• 期：1-3
• 页码：99-107
• 全文大小：728 K

文摘

Pressure-sensitive biological response is simulated in “rotating-cup” bioreactors with unidirectional modulations in compressive stress at the cylindrical wall that stimulate bone-tissue growth. Anchorage-dependent mammalian cells (i) adhere to a protein coating, (ii) receive nutrients and oxygen from an aqueous medium via radial diffusion toward the active surface, and (iii) respond to physiological modulations in centrifual-force-induced fluid pressure at the cell/aqueous-medium interface. This process is modeled by the classic diffusion equation (i.e., Fick's second law), with a time-dependent reaction/diffusion boundary condition at the wall. Non-reversing angular velocity modulations resemble pulsations at physiological frequencies. Computer simulations of nutrient consumption profiles suggest that rotational bioreactor designs should consider the effects of normal stress when the pressure-sensitive Damköhler number (i.e., ratio of the pressure-dependent zeroth-order rate of nutrient consumption relative to the rate of nutrient diffusion toward active cells adhered to the cylindrical wall), evaluated under steady rotation, is greater than ≈ 10–20 % of the stress-free Damköhler number (i.e., β_0,1st-order = 0.025) for simple 1st-order stress-free kinetics, and ≈ 1 % of the stress-free Damköhler number (i.e., β_0,2nd-order = 0.40) for complex 2nd-order stress-free nutrient consumption. When the peak-to-peak amplitude of angular velocity modulations of the cylindrical wall is the same as or larger than the angular velocity for steady rotation, the effect of non-reversing centrifugal-force-induced dynamic normal stress in rotational bioreactors, superimposed on steady rotation, can be significant when one is below the critical value of the pressure-sensitive Damköhler number that has been identified under steady rotation.