Preserving the functionality of hepatocytes in vitro poses a significant challenge in liver tissue engineering and bioartificial liver,as these cells rapidly lose their metabolic and functional characteristics after i...Preserving the functionality of hepatocytes in vitro poses a significant challenge in liver tissue engineering and bioartificial liver,as these cells rapidly lose their metabolic and functional characteristics after isolation.Inspired by the macroporous structures found in native liver tissues,here we develop synthetic hydrogel scaffolds that closely mimic the liver’s structural organization through the phase separation between polyethylene glycol(PEG)and polysaccharides.Our hydrogels exhibit interconnected macroporous structures and appropriate mechanical properties,providing an optimal microenvironment conducive to hepatocyte adhesion and the formation of sizable aggregates.Compared to two-dimensional hepatocyte cultures,enhanced functionalities of hepatocytes cultured in our macroporous hydrogels were observed for 14 days,as evidenced by quantitative reverse-transcription–polymerase chain reactions(qRT-PCR),immunofluorescence,and enzyme linked immunosorbent assay(ELISA)analyses.Protein sequencing data further confirmed the establishment of cell–cell interactions among hepatocytes when cultured in our hydrogels.Notably,these hepatocytes maintained a protein expression lineage that closely resembled freshly isolated hepatocytes,particularly in the Notch and tumor necrosis factor(TNF)signaling pathways.These results suggest that the macroporous hydrogels are attractive scaffolds for liver tissue engineering.展开更多
Macroporous hydrogels are water-swollen polymer networks with porous structures beyond the mesh size.They provide high specific surface areas and hieratical mass transfer channels which are desired for emerging applic...Macroporous hydrogels are water-swollen polymer networks with porous structures beyond the mesh size.They provide high specific surface areas and hieratical mass transfer channels which are desired for emerging applications including cell culturing,bio-separation,and drug delivery.A variety of approaches have been developed to fabricate macroporous hydrogels,including gas foaming,porogen templating,phase separation,3D printing,etc.Alternatively,ice templating utilizes the crystallization of water as the porogenation mechanism which doesn't need the leaching of porogens.展开更多
基金funded by the National Key R&D Program of China(No.2020YFA0908100)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(Nos.JNL2022004A,JNL2022019B)Shandong Provincial Laboratory Project(No.SYS202202).
文摘Preserving the functionality of hepatocytes in vitro poses a significant challenge in liver tissue engineering and bioartificial liver,as these cells rapidly lose their metabolic and functional characteristics after isolation.Inspired by the macroporous structures found in native liver tissues,here we develop synthetic hydrogel scaffolds that closely mimic the liver’s structural organization through the phase separation between polyethylene glycol(PEG)and polysaccharides.Our hydrogels exhibit interconnected macroporous structures and appropriate mechanical properties,providing an optimal microenvironment conducive to hepatocyte adhesion and the formation of sizable aggregates.Compared to two-dimensional hepatocyte cultures,enhanced functionalities of hepatocytes cultured in our macroporous hydrogels were observed for 14 days,as evidenced by quantitative reverse-transcription–polymerase chain reactions(qRT-PCR),immunofluorescence,and enzyme linked immunosorbent assay(ELISA)analyses.Protein sequencing data further confirmed the establishment of cell–cell interactions among hepatocytes when cultured in our hydrogels.Notably,these hepatocytes maintained a protein expression lineage that closely resembled freshly isolated hepatocytes,particularly in the Notch and tumor necrosis factor(TNF)signaling pathways.These results suggest that the macroporous hydrogels are attractive scaffolds for liver tissue engineering.
基金supported by the National Natural Science Foundation of China(grant Nos.52273112,U20A6001,22105167)the Start-up funding of Ningbo Research Institute of Zhejiang University(grant No.20201203Z0193).
文摘Macroporous hydrogels are water-swollen polymer networks with porous structures beyond the mesh size.They provide high specific surface areas and hieratical mass transfer channels which are desired for emerging applications including cell culturing,bio-separation,and drug delivery.A variety of approaches have been developed to fabricate macroporous hydrogels,including gas foaming,porogen templating,phase separation,3D printing,etc.Alternatively,ice templating utilizes the crystallization of water as the porogenation mechanism which doesn't need the leaching of porogens.
