Tissue engineered bone: Measurement of nutrient transport in three-dimensional matrices

2003 
The classic paradigm for in vitro tissue engineer- ing of bone involves the isolation and culture of donor osteoblasts or osteoprogenitor cells within three-dimen- sional (3D) scaffold biomaterials under conditions that sup- port 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 forma- tion. In this study, we have developed a basic one-dimen- sional (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. Inter- nal fluid perfusion within modeled scaffolds increased rap- idly with increasing pore volume and pore diameter to a maximum of approximately 1% of external fluid flow. In contrast, internal perfusion decreased significantly with in- creasing pore channel tortuosity. Calculations of associated nutrient flux indicate that static 3D culture and some inap- propriately designed dynamic culture environments lead to regions of insufficient nutrient concentration to maintain cell viability, and can result in steep nutrient concentration gra- dients within the modeled constructs. These quantitative studies provide a basis for development of new dynamic culture methodologies to overcome the limitations of pas- sive nutrient diffusion in 3D cell-scaffold composite systems proposed for in vitro tissue engineering of bone. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 357-367, 2003
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