title: Application of open porous poly(D,L-lactide-co-glycolide) microspheres and the strategy of hydrophobic seeding in hepatic tissue cultivation.
abstract: In this article, porous poly(D,L-lactide-co-glycolide) (PLGA) microsphere scaffolds with a size of ∼ 400 μm and pores of ∼ 20 μm were prepared for constructing injectable three-dimensional hepatocyte spheroids. The porous sites of PLGA microspheres provided a spatial space for hepatocyte distribution. Hepatocytes spheroids were cocultured with human umbilical vein endothelial cell, bone marrow mesenchymal stem cell, or NIH/3T3 cells by combining the porous PLGA microspheres with the relatively hydrophobic culture strategy. The combination of open porous microspheres, hepatocytes, and nonparenchymal cells was demonstrated for application in functional hepatic tissue reconstruction. Hepatocellular-specific functions can sustained up to 2 weeks in the support of coculturing with nonparenchymal cells. The spheroidal hepatocyte coculture system had the advantages of an injectable delivery, higher cell seeding density, protection from exerted shear stress, better exchange of nutrients, oxygen and metabolites, and heterotypic cell-cell contact within and between microspheres.
authors.affiliation: Institute of Biomedical Engineering, College of Engineering, College of Medicine, National Taiwan University, Taiwan.
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Chou
authors.forename: Chin-Hsiung
authors.initials: CH
authors.lastname: Hsieh
authors.forename: Peng-Lin
authors.initials: PL
authors.lastname: Yeh
authors.forename: Po-Cheng
authors.initials: PC
authors.lastname: Chen
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Yi-You
authors.initials: YY
authors.lastname: Huang
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005453:Fluorescence; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects*; D019344:Lactic Acid / Q000494:pharmacology*; D008099:Liver / Q000254:growth & development*; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D041681:NIH 3T3 Cells; D017711:Nonlinear Dynamics; D010316:Particle Size; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D023822:Tissue Engineering / Q000379:methods*; D014508:Urea / Q000378:metabolism
chemical_list: D000418:Albumins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D014508:Urea
keywords: 3D-coculture; BMMSC; HUVEC; hepatocyte cultivation; porous PLGA microspheres