Optimizing the medium perfusion rate in bone tissue engineering bioreactors

Warren L Grayson, Darja Marolt, Sarindr Bhumiratana, Mirjam Fröhlich, X. Edward Guo, Gordana Vunjak-Novakovic

Research output: Contribution to journalArticle

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 1,800μm/s), corresponding to estimated initial shear stresses ranging from 0.6 to 20mPa. 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 800μm/s yielded the best overall osteogenic responses. Using mathematical models, we determined that even at the lowest flow velocity (80μm/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.

Original languageEnglish (US)
Pages (from-to)1159-1170
Number of pages12
JournalBiotechnology and Bioengineering
Volume108
Issue number5
DOIs
StatePublished - May 2011

Fingerprint

Bioreactors
Tissue Engineering
Tissue engineering
Flow velocity
Bone
Perfusion
Bone and Bones
Regenerative Medicine
Hydrodynamics
Tissue
Cell Communication
Cell Survival
Theoretical Models
Gases
Grafts
Oxygen
Transplants
Phenotype
Gene Expression
Nutrients

Keywords

  • Bioreactor
  • Bone
  • Perfusion
  • Tissue engineering

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Grayson, W. L., Marolt, D., Bhumiratana, S., Fröhlich, M., Guo, X. E., & Vunjak-Novakovic, G. (2011). Optimizing the medium perfusion rate in bone tissue engineering bioreactors. Biotechnology and Bioengineering, 108(5), 1159-1170. https://doi.org/10.1002/bit.23024

Optimizing the medium perfusion rate in bone tissue engineering bioreactors. / Grayson, Warren L; Marolt, Darja; Bhumiratana, Sarindr; Fröhlich, Mirjam; Guo, X. Edward; Vunjak-Novakovic, Gordana.

In: Biotechnology and Bioengineering, Vol. 108, No. 5, 05.2011, p. 1159-1170.

Research output: Contribution to journalArticle

Grayson, WL, Marolt, D, Bhumiratana, S, Fröhlich, M, Guo, XE & Vunjak-Novakovic, G 2011, 'Optimizing the medium perfusion rate in bone tissue engineering bioreactors', Biotechnology and Bioengineering, vol. 108, no. 5, pp. 1159-1170. https://doi.org/10.1002/bit.23024
Grayson, Warren L ; Marolt, Darja ; Bhumiratana, Sarindr ; Fröhlich, Mirjam ; Guo, X. Edward ; Vunjak-Novakovic, Gordana. / Optimizing the medium perfusion rate in bone tissue engineering bioreactors. In: Biotechnology and Bioengineering. 2011 ; Vol. 108, No. 5. pp. 1159-1170.
@article{b32b460b9a0e45c5b98eb23bbf44e045,
title = "Optimizing the medium perfusion rate in bone tissue engineering bioreactors",
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 1,800μm/s), corresponding to estimated initial shear stresses ranging from 0.6 to 20mPa. 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 800μm/s yielded the best overall osteogenic responses. Using mathematical models, we determined that even at the lowest flow velocity (80μm/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.",
keywords = "Bioreactor, Bone, Perfusion, Tissue engineering",
author = "Grayson, {Warren L} and Darja Marolt and Sarindr Bhumiratana and Mirjam Fr{\"o}hlich and Guo, {X. Edward} and Gordana Vunjak-Novakovic",
year = "2011",
month = "5",
doi = "10.1002/bit.23024",
language = "English (US)",
volume = "108",
pages = "1159--1170",
journal = "Biotechnology and Bioengineering",
issn = "0006-3592",
publisher = "Wiley-VCH Verlag",
number = "5",

}

TY - JOUR

T1 - Optimizing the medium perfusion rate in bone tissue engineering bioreactors

AU - Grayson, Warren L

AU - Marolt, Darja

AU - Bhumiratana, Sarindr

AU - Fröhlich, Mirjam

AU - Guo, X. Edward

AU - Vunjak-Novakovic, Gordana

PY - 2011/5

Y1 - 2011/5

N2 - 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 1,800μm/s), corresponding to estimated initial shear stresses ranging from 0.6 to 20mPa. 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 800μm/s yielded the best overall osteogenic responses. Using mathematical models, we determined that even at the lowest flow velocity (80μm/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.

AB - 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 1,800μm/s), corresponding to estimated initial shear stresses ranging from 0.6 to 20mPa. 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 800μm/s yielded the best overall osteogenic responses. Using mathematical models, we determined that even at the lowest flow velocity (80μm/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.

KW - Bioreactor

KW - Bone

KW - Perfusion

KW - Tissue engineering

UR - http://www.scopus.com/inward/record.url?scp=79953127869&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953127869&partnerID=8YFLogxK

U2 - 10.1002/bit.23024

DO - 10.1002/bit.23024

M3 - Article

C2 - 21449028

AN - SCOPUS:79953127869

VL - 108

SP - 1159

EP - 1170

JO - Biotechnology and Bioengineering

JF - Biotechnology and Bioengineering

SN - 0006-3592

IS - 5

ER -