title: Transient inter-cellular polymeric linker.
abstract: Three-dimensional (3D) tissue-engineered constructs with bio-mimicry cell-cell and cell-matrix interactions are useful in regenerative medicine. In cell-dense and matrix-poor tissues of the internal organs, cells support one another via cell-cell interactions, supplemented by small amount of the extra-cellular matrices (ECM) secreted by the cells. Here we connect HepG2 cells directly but transiently with inter-cellular polymeric linker to facilitate cell-cell interaction and aggregation. The linker consists of a non-toxic low molecular-weight polyethyleneimine (PEI) backbone conjugated with multiple hydrazide groups that can aggregate cells within 30 min by reacting with the aldehyde handles on the chemically modified cell-surface glycoproteins. The cells in the cellular aggregates proliferated; and maintained the cortical actin distribution of the 3D cell morphology while non-aggregated cells died over 7 days of suspension culture. The aggregates lost distinguishable cell-cell boundaries within 3 days; and the ECM fibers became visible around cells from day 3 onwards while the inter-cellular polymeric linker disappeared from the cell surfaces over time. The transient inter-cellular polymeric linker can be useful for forming 3D cellular and tissue constructs without bulk biomaterials or extensive network of engineered ECM for various applications.
authors.affiliation: Institute of Biotechnology and Nanotechnology, A*STAR, The Nanos, Singapore.
authors.forename: Siew-Min
authors.initials: SM
authors.lastname: Ong
authors.forename: Lijuan
authors.initials: L
authors.lastname: He
authors.forename: Nguyen Thi
authors.initials: NT
authors.lastname: Thuy Linh
authors.forename: Yee-Han
authors.initials: YH
authors.lastname: Tee
authors.forename: Talha
authors.initials: T
authors.lastname: Arooz
authors.forename: Guping
authors.initials: G
authors.lastname: Tang
authors.forename: Choon-Hong
authors.initials: CH
authors.lastname: Tan
authors.forename: Hanry
authors.initials: H
authors.lastname: Yu
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007452:Iodates / Q000737:chemistry / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D007452:Iodates; D011108:Polymers; D011094:Polyethyleneimine; D003094:Collagen; D006909:Hydroxyproline