Liver-assist device with a microfluidics-based vascular bed in an animal model

Wen Ming Hsu, Amedeo Carraro, Katherine M. Kulig, Mark L. Miller, Mohammad Kaazempur-Mofrad, Eli Weinberg, Fateh Entabi, Hassan Albadawi, Michael T. Watkins, Jeffrey T. Borenstein, Joseph P. Vacanti, Craig Neville

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Objective: This study evaluates a novel liver-assist device platform with a microfluidics-modeled vascular network in a femoral arteriovenous shunt in rats. Summary of background data: Liver-assist devices in clinical trials that use pumps to force separated plasma through packed beds of parenchymal cells exhibited significant necrosis with a negative impact on function. Methods: Microelectromechanical systems technology was used to design and fabricate a liver-assist device with a vascular network that supports a hepatic parenchymal compartment through a nanoporous membrane. Sixteen devices with rat primary hepatocytes and 12 with human HepG2/C3A cells were tested in athymic rats in a femoral arteriovenous shunt model. Several parenchymal tube configurations were evaluated for pressure profile and cell survival. The blood flow pattern and perfusion status of the devices was examined by laser Doppler scanning. Cell viability and serum protein secretion functions were assessed. Results: Femoral arteriovenous shunt was successfully established in all animals. Blood flow was homogeneous through the vascular bed and replicated native flow patterns. Survival of seeded liver cells was highly dependent on parenchymal chamber pressures. The tube configuration that generated the lowest pressure supported excellent cell survival and function. Conclusions: This device is the first to incorporate a microfluidics network in the systemic circulatory system. The microvascular network supported viability and function of liver cells in a short-term ex vivo model. Parenchymal chamber pressure generated in an arteriovenous shunt model is a critical parameter that affects viability and must be considered in future designs. The microfluidics-based vascular network is a promising platform for generating a large-scale medical device capable of augmenting liver function in a clinical setting.

Original languageEnglish (US)
Pages (from-to)351-357
Number of pages7
JournalAnnals of Surgery
Volume252
Issue number2
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

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Microfluidics
Blood Vessels
Animal Models
Equipment and Supplies
Liver
Thigh
Pressure
Cell Survival
Nude Rats
Hep G2 Cells
Cardiovascular System
Microvessels
Blood Proteins
Hepatocytes
Lasers
Necrosis
Perfusion
Clinical Trials
Technology
Membranes

ASJC Scopus subject areas

  • Surgery

Cite this

Hsu, W. M., Carraro, A., Kulig, K. M., Miller, M. L., Kaazempur-Mofrad, M., Weinberg, E., ... Neville, C. (2010). Liver-assist device with a microfluidics-based vascular bed in an animal model. Annals of Surgery, 252(2), 351-357. https://doi.org/10.1097/SLA.0b013e3181e982ba

Liver-assist device with a microfluidics-based vascular bed in an animal model. / Hsu, Wen Ming; Carraro, Amedeo; Kulig, Katherine M.; Miller, Mark L.; Kaazempur-Mofrad, Mohammad; Weinberg, Eli; Entabi, Fateh; Albadawi, Hassan; Watkins, Michael T.; Borenstein, Jeffrey T.; Vacanti, Joseph P.; Neville, Craig.

In: Annals of Surgery, Vol. 252, No. 2, 01.08.2010, p. 351-357.

Research output: Contribution to journalArticle

Hsu, WM, Carraro, A, Kulig, KM, Miller, ML, Kaazempur-Mofrad, M, Weinberg, E, Entabi, F, Albadawi, H, Watkins, MT, Borenstein, JT, Vacanti, JP & Neville, C 2010, 'Liver-assist device with a microfluidics-based vascular bed in an animal model', Annals of Surgery, vol. 252, no. 2, pp. 351-357. https://doi.org/10.1097/SLA.0b013e3181e982ba
Hsu WM, Carraro A, Kulig KM, Miller ML, Kaazempur-Mofrad M, Weinberg E et al. Liver-assist device with a microfluidics-based vascular bed in an animal model. Annals of Surgery. 2010 Aug 1;252(2):351-357. https://doi.org/10.1097/SLA.0b013e3181e982ba
Hsu, Wen Ming ; Carraro, Amedeo ; Kulig, Katherine M. ; Miller, Mark L. ; Kaazempur-Mofrad, Mohammad ; Weinberg, Eli ; Entabi, Fateh ; Albadawi, Hassan ; Watkins, Michael T. ; Borenstein, Jeffrey T. ; Vacanti, Joseph P. ; Neville, Craig. / Liver-assist device with a microfluidics-based vascular bed in an animal model. In: Annals of Surgery. 2010 ; Vol. 252, No. 2. pp. 351-357.
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abstract = "Objective: This study evaluates a novel liver-assist device platform with a microfluidics-modeled vascular network in a femoral arteriovenous shunt in rats. Summary of background data: Liver-assist devices in clinical trials that use pumps to force separated plasma through packed beds of parenchymal cells exhibited significant necrosis with a negative impact on function. Methods: Microelectromechanical systems technology was used to design and fabricate a liver-assist device with a vascular network that supports a hepatic parenchymal compartment through a nanoporous membrane. Sixteen devices with rat primary hepatocytes and 12 with human HepG2/C3A cells were tested in athymic rats in a femoral arteriovenous shunt model. Several parenchymal tube configurations were evaluated for pressure profile and cell survival. The blood flow pattern and perfusion status of the devices was examined by laser Doppler scanning. Cell viability and serum protein secretion functions were assessed. Results: Femoral arteriovenous shunt was successfully established in all animals. Blood flow was homogeneous through the vascular bed and replicated native flow patterns. Survival of seeded liver cells was highly dependent on parenchymal chamber pressures. The tube configuration that generated the lowest pressure supported excellent cell survival and function. Conclusions: This device is the first to incorporate a microfluidics network in the systemic circulatory system. The microvascular network supported viability and function of liver cells in a short-term ex vivo model. Parenchymal chamber pressure generated in an arteriovenous shunt model is a critical parameter that affects viability and must be considered in future designs. The microfluidics-based vascular network is a promising platform for generating a large-scale medical device capable of augmenting liver function in a clinical setting.",
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AU - Weinberg, Eli

AU - Entabi, Fateh

AU - Albadawi, Hassan

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AU - Vacanti, Joseph P.

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