Engineering of in vitro 3D capillary beds by self-directed angiogenic sprouting

PLoS One. 2012;7(12):e50582. doi: 10.1371/journal.pone.0050582. Epub 2012 Dec 4.

Abstract

In recent years, microfluidic systems have been used to study fundamental aspects of angiogenesis through the patterning of single-layered, linear or geometric vascular channels. In vivo, however, capillaries exist in complex, three-dimensional (3D) networks, and angiogenic sprouting occurs with a degree of unpredictability in all x,y,z planes. The ability to generate capillary beds in vitro that can support thick, biological tissues remains a key challenge to the regeneration of vital organs. Here, we report the engineering of 3D capillary beds in an in vitro microfluidic platform that is comprised of a biocompatible collagen I gel supported by a mechanical framework of alginate beads. The engineered vessels have patent lumens, form robust ~1.5 mm capillary networks across the devices, and support the perfusion of 1 µm fluorescent beads through them. In addition, the alginate beads offer a modular method to encapsulate and co-culture cells that either promote angiogenesis or require perfusion for cell viability in engineered tissue constructs. This laboratory-constructed vascular supply may be clinically significant for the engineering of capillary beds and higher order biological tissues in a scalable and modular manner.

Publication types

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

MeSH terms

  • Alginates
  • Capillaries / growth & development*
  • Cells, Cultured
  • Coculture Techniques
  • Glucuronic Acid
  • Hexuronic Acids
  • Humans
  • Immunohistochemistry
  • Microfluidics
  • Neovascularization, Physiologic*
  • Tissue Scaffolds

Substances

  • Alginates
  • Hexuronic Acids
  • Glucuronic Acid

Grant support

This study was supported in part by a NSF Science and Technology Center (EBICS) grant and the Singapore-MIT Alliance (SMART). JMC acknowledges financial support from the Singapore Agency for Science, Technology and Research (A*STAR) National Science Scholarship, and the 2011 L’Oreal-UNESCO For Women In Science Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.