Bioengineering a cryogel-derived bioartificial liver using particle image velocimetry defined fluid dynamics

Flavia Bonalumi; Cyril Crua; Irina N. Savina; Nathan Davies; Abeba Habstesion; Maurizio Santini; Stephanie Fest-Santini; Susan Sandeman

doi:10.1016/j.msec.2021.111983

Bioengineering a cryogel-derived bioartificial liver using particle image velocimetry defined fluid dynamics

Flavia Bonalumi, Cyril Crua, Irina N. Savina, Nathan Davies, Abeba Habstesion, Maurizio Santini, Stephanie Fest-Santini, Susan Sandeman

Research output: Contribution to journal › Article › peer-review

Abstract

Bioartificial Liver (BAL) devices are extracorporeal systems designed to support or recover hepatic function in patients with liver failure. The design of an effective BAL remains an open challenge since it requires a complex co-optimisation of cell colonisation, biomaterial scaffold and BAL fluid dynamics. Building on previous evidence of suitability as a blood perfusion device for detoxification, the current study investigated the use of RGD-containing p(HEMA)-alginate cryogels as BAL scaffolds. Cryogels were modified with alginate to reduce protein fouling and functionalised with an RGD-containing peptide to increase hepatocyte adhesion. A novel approach for characterisation of the internal flow through the porous matrix was developed by employing Particle Image Velocimetry (PIV) to visualise flow inside cryogels. Based on PIV results, which showed the laminar nature of flow inside cryogel pores, a multi-layered bioreactor composed of spaced cryogel discs was designed to improve blood/hepatocyte mass exchange. The stacked bioreactor showed a significantly higher production of albumin and urea compared to the column version, with improved cell colonisation and proliferation over time. The cell-free cryogel-based device was tested for safety in a bile-duct ligation model of liver cirrhosis. Thus, a stacked bioreactor prototype was developed based on a surface-engineered cryogel design with optimised fluid dynamics for BAL use.

Original language	English
Article number	111983
Journal	Materials Science and Engineering C
Volume	123
DOIs	https://doi.org/10.1016/j.msec.2021.111983
Publication status	Published - 23 Feb 2021

Bibliographical note

Funding Information:
Flavia Bonalumi was funded by a University of Brighton PhD studentship. This work received funding from the University of Brighton Centre for Stress and Age-related Disease. The authors would like to thank Dr. Arvind Patel (University of Glasgow) for kindly providing the HHLs, and Marie Drevet Mulard (Institut d'optique Graduate School) for her contribution to the ?PIV measurements.

Publisher Copyright:
© 2021 Elsevier B.V.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

Alginate
BDL model
Bioartificial liver
Cell scaffold
Cryogels
RGD-peptide
μPIV

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10.1016/j.msec.2021.111983

Bonalumi 2021 postprintAccepted author manuscript, 2.27 MBLicence: CC BY-NC-ND

Cite this

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title = "Bioengineering a cryogel-derived bioartificial liver using particle image velocimetry defined fluid dynamics",

abstract = "Bioartificial Liver (BAL) devices are extracorporeal systems designed to support or recover hepatic function in patients with liver failure. The design of an effective BAL remains an open challenge since it requires a complex co-optimisation of cell colonisation, biomaterial scaffold and BAL fluid dynamics. Building on previous evidence of suitability as a blood perfusion device for detoxification, the current study investigated the use of RGD-containing p(HEMA)-alginate cryogels as BAL scaffolds. Cryogels were modified with alginate to reduce protein fouling and functionalised with an RGD-containing peptide to increase hepatocyte adhesion. A novel approach for characterisation of the internal flow through the porous matrix was developed by employing Particle Image Velocimetry (PIV) to visualise flow inside cryogels. Based on PIV results, which showed the laminar nature of flow inside cryogel pores, a multi-layered bioreactor composed of spaced cryogel discs was designed to improve blood/hepatocyte mass exchange. The stacked bioreactor showed a significantly higher production of albumin and urea compared to the column version, with improved cell colonisation and proliferation over time. The cell-free cryogel-based device was tested for safety in a bile-duct ligation model of liver cirrhosis. Thus, a stacked bioreactor prototype was developed based on a surface-engineered cryogel design with optimised fluid dynamics for BAL use.",

keywords = "Alginate, BDL model, Bioartificial liver, Cell scaffold, Cryogels, RGD-peptide, μPIV",

author = "Flavia Bonalumi and Cyril Crua and Savina, {Irina N.} and Nathan Davies and Abeba Habstesion and Maurizio Santini and Stephanie Fest-Santini and Susan Sandeman",

note = " Funding Information: Flavia Bonalumi was funded by a University of Brighton PhD studentship. This work received funding from the University of Brighton Centre for Stress and Age-related Disease. The authors would like to thank Dr. Arvind Patel (University of Glasgow) for kindly providing the HHLs, and Marie Drevet Mulard (Institut d'optique Graduate School) for her contribution to the ?PIV measurements. Publisher Copyright: {\textcopyright} 2021 Elsevier B.V. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

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doi = "10.1016/j.msec.2021.111983",

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AU - Habstesion, Abeba

AU - Santini, Maurizio

AU - Fest-Santini, Stephanie

AU - Sandeman, Susan

N1 - Funding Information: Flavia Bonalumi was funded by a University of Brighton PhD studentship. This work received funding from the University of Brighton Centre for Stress and Age-related Disease. The authors would like to thank Dr. Arvind Patel (University of Glasgow) for kindly providing the HHLs, and Marie Drevet Mulard (Institut d'optique Graduate School) for her contribution to the ?PIV measurements. Publisher Copyright: © 2021 Elsevier B.V. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

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Y1 - 2021/2/23

N2 - Bioartificial Liver (BAL) devices are extracorporeal systems designed to support or recover hepatic function in patients with liver failure. The design of an effective BAL remains an open challenge since it requires a complex co-optimisation of cell colonisation, biomaterial scaffold and BAL fluid dynamics. Building on previous evidence of suitability as a blood perfusion device for detoxification, the current study investigated the use of RGD-containing p(HEMA)-alginate cryogels as BAL scaffolds. Cryogels were modified with alginate to reduce protein fouling and functionalised with an RGD-containing peptide to increase hepatocyte adhesion. A novel approach for characterisation of the internal flow through the porous matrix was developed by employing Particle Image Velocimetry (PIV) to visualise flow inside cryogels. Based on PIV results, which showed the laminar nature of flow inside cryogel pores, a multi-layered bioreactor composed of spaced cryogel discs was designed to improve blood/hepatocyte mass exchange. The stacked bioreactor showed a significantly higher production of albumin and urea compared to the column version, with improved cell colonisation and proliferation over time. The cell-free cryogel-based device was tested for safety in a bile-duct ligation model of liver cirrhosis. Thus, a stacked bioreactor prototype was developed based on a surface-engineered cryogel design with optimised fluid dynamics for BAL use.

AB - Bioartificial Liver (BAL) devices are extracorporeal systems designed to support or recover hepatic function in patients with liver failure. The design of an effective BAL remains an open challenge since it requires a complex co-optimisation of cell colonisation, biomaterial scaffold and BAL fluid dynamics. Building on previous evidence of suitability as a blood perfusion device for detoxification, the current study investigated the use of RGD-containing p(HEMA)-alginate cryogels as BAL scaffolds. Cryogels were modified with alginate to reduce protein fouling and functionalised with an RGD-containing peptide to increase hepatocyte adhesion. A novel approach for characterisation of the internal flow through the porous matrix was developed by employing Particle Image Velocimetry (PIV) to visualise flow inside cryogels. Based on PIV results, which showed the laminar nature of flow inside cryogel pores, a multi-layered bioreactor composed of spaced cryogel discs was designed to improve blood/hepatocyte mass exchange. The stacked bioreactor showed a significantly higher production of albumin and urea compared to the column version, with improved cell colonisation and proliferation over time. The cell-free cryogel-based device was tested for safety in a bile-duct ligation model of liver cirrhosis. Thus, a stacked bioreactor prototype was developed based on a surface-engineered cryogel design with optimised fluid dynamics for BAL use.

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KW - Cell scaffold

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DO - 10.1016/j.msec.2021.111983

M3 - Article

AN - SCOPUS:85102023407

SN - 0928-4931

VL - 123

JO - Materials Science and Engineering C

JF - Materials Science and Engineering C

M1 - 111983

ER -

Bioengineering a cryogel-derived bioartificial liver using particle image velocimetry defined fluid dynamics

Abstract

Bibliographical note

Keywords

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