Dense Type I Collagen Matrices That Support Cellular Remodeling and Microfabrication for Studies of Tumor Angiogenesis and Vasculogenesis in Vitro

Biomaterials. 2010 Nov;31(33):8596-607. doi: 10.1016/j.biomaterials.2010.07.072. Epub 2010 Aug 19.

Abstract

Type I collagen is a favorable substrate for cell adhesion and growth and is remodelable by many tissue cells; these characteristics make it an attractive material for the study of dynamic cellular processes. Low mass fraction (1.0-3.0 mg/ml), hydrated collagen matrices used for three-dimensional cell culture permit cellular movement and remodeling, but their microstructure and mechanics fail to mimic characteristics of many extracellular matrices in vivo and limit the definition of fine-scale geometrical features (<1 mm) within scaffolds. In this study, we worked with hydrated type I collagen at mass fractions between 3.0 and 20 mg/ml to define the range of densities over which the matrices support both microfabrication and cellular remodeling. We present pore and fiber dimensions based on confocal microscopy and longitudinal modulus and hydraulic permeability based on confined compression. We demonstrate faithful reproduction of simple pores of 50 μm-diameter over the entire range and formation of functional microfluidic networks for mass fractions of at least 10.0 mg/ml. We present quantitative characterization of the rate and extent of cellular remodelability using human umbilical vein endothelial cells. Finally, we present a co-culture with tumor cells and discuss the implications of integrating microfluidic control within scaffolds as a tool to study spatial and temporal signaling during tumor angiogenesis and vascularization of tissue engineered constructs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Coculture Techniques
  • Collagen Type I / pharmacology*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Gels
  • Humans
  • Mechanical Phenomena / drug effects
  • Microfluidics
  • Microscopy, Confocal
  • Microtechnology / methods*
  • Neoplasms / blood supply*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / pathology*
  • Neovascularization, Physiologic / drug effects*
  • Porosity / drug effects
  • Rats
  • Time Factors

Substances

  • Collagen Type I
  • Gels