Botchwey Edward A, Pollack Solomon R, Levine Elliot M, Johnston Eric D, 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. 2004 May 1;69(2):205-15. doi: 10.1002/jbm.a.10163.
Tissue engineering has emerged as a viable alternative to the problem of organ and tissue shortage. Our laboratory has developed matrices for bone tissue engineering based on sintered spherical particles and, using bioreactor technology, has demonstrated the ability to produce highly mineralized matrices in vitro. In this study, porous microcapsule scaffolds were developed for bone tissue engineering in the high aspect ratio vessel rotating bioreactor. The motion of individual microcapsules as well as scaffolds in the bioreactor were studied by numerical simulation and in situ imaging analysis. Results show that spherical microcapsules with density less than the surrounding fluid exhibited two motions: (1) a periodic circular orbit with tangential speed equal to the free fall speed of the particle, and (2) an inward radial migration of the circular orbit toward the center of the bioreactor vessel. Lighter-than-water scaffolds were fabricated by sintering poly(lactic-co-glycolic acid) hollow microcarriers with diameter from 500 to 860 microm into a fixed three-dimensional geometry with approximately 30% pore volume and 180 to 190 microm median pore size. Scaffolds were fabricated with aggregate densities ranging from 0.65 g/mL and 0.99 g/mL by appropriate combinations of hollow and solid microcarriers within the scaffold. Scaffold velocity in the bioreactor for the above range of densities was accurately predicted by numerical simulation and ranged from 100 mm/s to 3 mm/s. Maximum shear stress estimation due to media flow over the exterior of the scaffold ranged from 0.3 N/m(2) to 0.006 N/m(2). Internal perfusion velocity through scaffolds also was calculated and ranged from 13 mm/s to 0.2 mm/s. Estimates of maximum interior shear stress ranged from 0.03 to 0.0007 N/m(2). These analytical methods provide an excellent vehicle for the study of bone tissue synthesis in three-dimensional culture with fluid flow.
组织工程学已成为解决器官和组织短缺问题的一种可行替代方案。我们的实验室已基于烧结球形颗粒开发出用于骨组织工程的基质，并利用生物反应器技术证明了在体外生产高度矿化基质的能力。在本研究中，为高纵横比容器旋转生物反应器中的骨组织工程开发了多孔微胶囊支架。通过数值模拟和原位成像分析研究了生物反应器中单个微胶囊以及支架的运动。结果表明，密度小于周围流体的球形微胶囊表现出两种运动：（1）切向速度等于颗粒自由落体速度的周期性圆形轨道，以及（2）圆形轨道向生物反应器容器中心的向内径向迁移。通过将直径为500至860微米的聚（乳酸-共-乙醇酸）中空微载体烧结成具有约30％孔隙体积和180至190微米中位孔径的固定三维几何形状，制备了比水轻的支架。通过在支架内适当组合中空和实心微载体，制备了聚集密度范围为0.65 g/mL至0.99 g/mL的支架。通过数值模拟准确预测了上述密度范围内生物反应器中支架的速度，范围为100 mm/s至3 mm/s。由于培养基在支架外部流动而产生的最大剪应力估计范围为0.3 N/m²至0.006 N/m²。还计算了通过支架的内部灌注速度，范围为13 mm/s至0.2 mm/s。最大内部剪应力估计范围为0.03至0.0007 N/m²。这些分析方法为研究流体流动下三维培养中的骨组织合成提供了极好的手段。
