Optimization of 3-D hepatocyte culture by controlling the physical and chemical properties of the extra-cellular matrices.
Hepatocytes are anchorage-dependent cells sensitive to microenvironment; the control of the physicochemical properties of the extra-cellular matrices may be useful to the maintenance of hepatocyte functions in vitro for various applications. In a microcapsule-based 3-D hepatocyte culture microenvironment, we could control the physical properties of the collagen nano-fibres by fine-tuning the complex-coacervation reaction between methylated collagen and terpolymer of hydroxylethyl methacrylate-methyl methacrylate-methylacrylic acid. The physical properties of the nano-fibres were quantitatively characterized using back-scattering confocal microscopy to help optimize the physical support for hepatocyte functions. We further enhanced the chemical properties of the collagen nano-fibres by incorporating galactose onto collagen, which can specifically interact with the asialoglycoprotein receptor on hepatocytes. By correlating a range of collagen nano-fibres of different physicochemical properties with hepatocyte functions, we have identified a specific combination of methylated and galactosylated collagen nano-fibres optimal for maintaining hepatocyte functions in vitro. A model of how the physical and chemical supports interplay to maintain hepatocyte functions is discussed.
Ng
Susanne
S
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, #04-01 Singapore 138669, Singapore.
Wu
Ying-Nan
YN
Zhou
Yi
Y
Toh
Yi-Er
YE
Ho
Zi-Zong
ZZ
Chia
Ser-Mien
SM
Zhu
Jian-Hang
JH
Mao
Hai-Quan
HQ
Yu
Hanry
H
D015660:7-Alkoxycoumarin O-Dealkylase / Q000737:chemistry; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000737:chemistry; D005109:Extracellular Matrix / Q000378:metabolism*; D005690:Galactose / Q000737:chemistry / Q000378:metabolism; D022781:Hepatocytes / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008297:Male; D008689:Methacrylates / Q000737:chemistry; D008745:Methylation; D020366:Methylmethacrylate / Q000737:chemistry; D008833:Microcirculation; D018613:Microscopy, Confocal; D008956:Models, Chemical; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012542:Scattering, Radiation
D008689:Methacrylates; D011108:Polymers; D020366:Methylmethacrylate; C008384:methacrylic acid; C005044:hydroxyethyl methacrylate; D003094:Collagen; D015660:7-Alkoxycoumarin O-Dealkylase; D005690:Galactose