Author/Editor		Grayson, Warren L; Marolt, Darja; Bhumiratana, Sarindr; Froehlich, Mirjam; Guo, Edward X; Vunjak-Novakovič, Gordana
Title		Optimizing the medium perfusion rate in bone tissue engineering bioreactors
Type		članek
Source		Biotechnol Bioeng
Vol. and No.		Letnik 108, št. 5
Publication year		2011
Volume		str. 1159-70
Language		eng
Abstract		There is a critical need to increase the size of bone grafts that can be cultured in vitro for use in regenerative medicine. Perfusion bioreactors have been used to improve the nutrient and gas transfer capabilities and reduce the size limitations inherent to static culture, as well as to modulate cellular responses by hydrodynamic shear. Our aim was to understand the effects of medium flow velocity on cellular phenotype and the formation of bone-like tissues in three-dimensional engineered constructs. We utilized custom-designed perfusion bioreactors to culture bone constructs for 5 weeks using a wide range of superficial flow velocities (80, 400, 800, 1,200, and 1,800 microm/s), corresponding to estimated initial shear stresses ranging from 0.6 to 20 mPa. Increasing the flow velocity significantly affected cell morphology, cell-cell interactions, matrix production and composition, and the expression of osteogenic genes. Within the range studied, the flow velocities ranging from 400 to 800 microm/s yielded the best overall osteogenic responses. Using mathematical models, we determined that even at the lowest flow velocity (80 microm/s) the oxygen provided was sufficient to maintain viability of the cells within the construct. Yet it was clear that this flow velocity did not adequately support the development of bone-like tissue. The complexity of the cellular responses found at different flow velocities underscores the need to use a range of evaluation parameters to determine the quality of engineered bone. Bioeng.
Descriptors		BIOREACTORS BONE TRANSPLANTATION ORGAN CULTURE PERFUSION OSTEOGENESIS STEM CELLS CELL SURVIVAL DNA CELL DIVISION GENE EXPRESSION IMMUNOHISTOCHEMISTRY