In vitro analysis of a hepatic device with intrinsic microvascular-based channels.
A novel microfluidics-based bilayer device with a discrete parenchymal chamber modeled upon hepatic organ architecture is described. The microfluidics network was designed using computational models to provide appropriate flow behavior based on physiological data from human microvasculature. Patterned silicon wafer molds were used to generate films with the vascular-based microfluidics network design and parenchymal chamber by soft lithography. The assembled device harbors hepatocytes behind a nanoporous membrane that permits transport of metabolites and small proteins while protecting them from the effects of shear stress. The device can sustain both human hepatoma cells and primary rat hepatocytes by continuous in vitro perfusion of medium, allowing proliferation and maintaining hepatic functions such as serum protein synthesis and metabolism. The design and fabrication processes are scalable, enabling the device concept to serve as both a platform technology for drug discovery and toxicity, and for the continuing development of an improved liver-assist device.
Carraro
Amedeo
A
Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.|Department of Surgical and Gastroenterological Sciences, University of Padua, School of Medicine, Padova, Italy.|Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street CPZN-4809, Boston, MA, 02114, USA.
Hsu
Wen-Ming
WM
Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.|Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.|Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street CPZN-4809, Boston, MA, 02114, USA.
Kulig
Katherine M
KM
Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.|Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street CPZN-4809, Boston, MA, 02114, USA.
Cheung
Wing S
WS
Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.|Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street CPZN-4809, Boston, MA, 02114, USA.
Miller
Mark L
ML
Harvard Medical School, Boston, MA, USA.
Weinberg
Eli J
EJ
Biomedical Engineering Center, Charles Stark Draper Laboratory, Cambridge, MA, USA.
Swart
Eric F
EF
Harvard Medical School, Boston, MA, USA.
Kaazempur-Mofrad
Mohammad
M
Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
Borenstein
Jeffrey T
JT
Biomedical Engineering Center, Charles Stark Draper Laboratory, Cambridge, MA, USA.
Vacanti
Joseph P
JP
Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.|Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street CPZN-4809, Boston, MA, 02114, USA.
Neville
Craig
C
Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. neville@helix.mgh.harvard.edu.|Harvard Medical School, Boston, MA, USA. neville@helix.mgh.harvard.edu.|Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street CPZN-4809, Boston, MA, 02114, USA. neville@helix.mgh.harvard.edu.
D000818:Animals; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D019164:Liver, Artificial; D008297:Male; D008567:Membranes, Artificial; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods*; D016062:Porosity; D051381:Rats; D011917:Rats, Inbred Lew; D012825:Silicon / Q000737:chemistry
D008567:Membranes, Artificial; D012825:Silicon