Cantini Marco, Fiore Gianfranco B, Redaelli Alberto, Soncini Monica
Department of Bioengineering, Politecnico di Milano, Milan, Italy.
Tissue Eng Part A. 2009 Mar;15(3):615-23. doi: 10.1089/ten.tea.2008.0027.
Computational fluid dynamic (CFD) techniques were used to optimize the microenvironment inside scaffolds for hematopoietic stem cell (HSC) culture in a perfusion bioreactor. These matrices are meant to be seeded with adherent bone marrow stromal cells and then co-cultivated with HSCs; the scaffold micro-architecture and the fluid-dynamic conditions have to be optimized to avoid non-adherent stem cells being dragged away while ensuring adequate nutrient supply. The insertion of longitudinal microchannels was tested as a tool to improve perfusion in a homogeneous porous scaffold. Models of microchannel-provided scaffolds, characterized by different values of geometric parameters concerning pores and channels, were built, and numerical fluid-dynamic and oxygen-transfer analyses were carried out. The results of the computations indicated that the microchannels created preferential paths for culture medium flow, causing low shear stresses and drag forces within the pores; meanwhile, they improved oxygen delivery by forcing its penetration into the scaffold bulk. In particular, an 85% porous, 3-mm-thick scaffold with 175-microm-diameter pores was considered; at a constant average drag force guaranteeing stem cell suspension inside this porous bulk, the addition of approximately 260-microm-diameter, 700-microm-spaced channels resulted in 34% higher oxygen partial pressure at the exit (approximately 135 vs 101 mmHg), maintaining a wall shear stress median value of approximately 0.14 mPa. The present work demonstrates the capacity of microchannel-provided scaffolds to ensure suitable conditions for HSC culture and shows that CFD methods are a valuable tool to retrieve significant clues for the design of the culture environment.
采用计算流体动力学（CFD）技术优化灌注生物反应器中用于造血干细胞（HSC）培养的支架内部微环境。这些基质旨在接种贴壁骨髓基质细胞，然后与造血干细胞共培养；必须优化支架的微观结构和流体动力学条件，以避免非贴壁干细胞被冲走，同时确保充足的营养供应。测试了插入纵向微通道作为改善均匀多孔支架灌注的一种手段。构建了具有不同孔隙和通道几何参数值的微通道支架模型，并进行了数值流体动力学和氧传递分析。计算结果表明，微通道为培养基流动创造了优先路径，在孔隙内产生低剪切应力和拖曳力；同时，通过迫使氧气渗透到支架主体中，改善了氧气输送。特别是，考虑了一种孔隙率为85%、厚度为3毫米、孔径为175微米的支架；在保证干细胞悬浮在该多孔主体内的恒定平均拖曳力下，添加直径约为260微米、间距为700微米的通道，出口处的氧分压提高了34%（约为135 vs 101 mmHg），壁面剪切应力中值保持在约0.14 mPa。本研究证明了微通道支架能够确保为造血干细胞培养提供合适条件，并表明CFD方法是获取培养环境设计重要线索的宝贵工具。
