Transient inter-cellular polymeric linker

Biomaterials. 2007 Sep;28(25):3656-67. doi: 10.1016/j.biomaterials.2007.04.034. Epub 2007 May 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Cell Adhesion / drug effects
  • Cell Aggregation / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Collagen / metabolism
  • Extracellular Matrix / chemistry
  • Humans
  • Hydroxyproline / metabolism
  • Iodates / chemistry
  • Iodates / pharmacology
  • Microscopy, Electron, Scanning
  • Molecular Structure
  • Polyethyleneimine / chemistry
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Polymers / pharmacology
  • Tissue Engineering / methods*

Substances

  • Biocompatible Materials
  • Iodates
  • Polymers
  • Polyethyleneimine
  • Collagen
  • Hydroxyproline