Botchwey Edward A, Dupree Melissa A, Pollack Solomon R, Levine Elliot M, Laurencin Cato T
Department of Biomedical Engineering, The University of Virginia, 400 Ray C. Hunt Drive, Suite 330, Charlottesville, Virginia 22903, USA.
J Biomed Mater Res A. 2003 Oct 1;67(1):357-67. doi: 10.1002/jbm.a.10111.
The classic paradigm for in vitro tissue engineering of bone involves the isolation and culture of donor osteoblasts or osteoprogenitor cells within three-dimensional (3D) scaffold biomaterials under conditions that support tissue growth and mineralized osteoid formation. Our studies focus on the development and utilization of new dynamic culture technologies to provide adequate nutrient flux within 3D scaffolds to support ongoing tissue formation. In this study, we have developed a basic one-dimensional (1D) model to characterize the efficiency of passive nutrient diffusion and transport flux to bone cells within 3D scaffolds under static and dynamic culture conditions. Internal fluid perfusion within modeled scaffolds increased rapidly with increasing pore volume and pore diameter to a maximum of approximately 1% of external fluid flow. In contrast, internal perfusion decreased significantly with increasing pore channel tortuosity. Calculations of associated nutrient flux indicate that static 3D culture and some inappropriately designed dynamic culture environments lead to regions of insufficient nutrient concentration to maintain cell viability, and can result in steep nutrient concentration gradients within the modeled constructs. These quantitative studies provide a basis for development of new dynamic culture methodologies to overcome the limitations of passive nutrient diffusion in 3D cell-scaffold composite systems proposed for in vitro tissue engineering of bone.
用于骨组织工程的经典体外范例涉及在支持组织生长和矿化类骨质形成的条件下，将供体成骨细胞或骨祖细胞分离并培养于三维（3D）支架生物材料中。我们的研究重点在于开发和利用新的动态培养技术，以在3D支架内提供充足的营养物质通量，从而支持持续的组织形成。在本研究中，我们构建了一个基本的一维（1D）模型，以表征在静态和动态培养条件下，3D支架内被动营养物质扩散和传输通量对骨细胞的效率。模拟支架内的内部流体灌注随着孔隙体积和孔径的增加而迅速增加，最高可达外部流体流量的约1%。相比之下，内部灌注随着孔隙通道曲折度的增加而显著降低。相关营养物质通量的计算表明，静态3D培养以及一些设计不当的动态培养环境会导致营养物质浓度不足以维持细胞活力的区域出现，并可能在模拟构建体中产生陡峭的营养物质浓度梯度。这些定量研究为开发新的动态培养方法提供了基础，以克服在用于骨组织工程的3D细胞-支架复合系统中被动营养物质扩散的局限性。
