Liver-assist device with a microfluidics-based vascular bed in an animal model.
OBJECTIVE
This study evaluates a novel liver-assist device platform with a microfluidics-modeled vascular network in a femoral arteriovenous shunt in rats.


BACKGROUND
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.
Hsu
Wen-Ming
WM
Department of Surgery and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
Carraro
Amedeo
A
Kulig
Katherine M
KM
Miller
Mark L
ML
Kaazempur-Mofrad
Mohammad
M
Weinberg
Eli
E
Entabi
Fateh
F
Albadawi
Hassan
H
Watkins
Michael T
MT
Borenstein
Jeffrey T
JT
Vacanti
Joseph P
JP
Neville
Craig
C
D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D019149:Bioreactors; D018929:Cell Culture Techniques; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005269:Femur / Q000098:blood supply / Q000601:surgery; D022781:Hepatocytes / Q000378:metabolism*; D017078:Laser-Doppler Flowmetry; D019164:Liver, Artificial; D008297:Male; D008833:Microcirculation; D044085:Microfluidics / Q000379:methods*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D011506:Proteins