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LETTERS
In situ collagen assembly for integrating
microfabricated three-dimensional
cell-seeded matrices
BRIAN M. GILLETTE, JACOB A. JENSEN, BEIXIAN TANG, GENEVIEVE J. YANG, ARDALAN BAZARGAN-LARI,
MING ZHONG AND SAMUEL K. SIA*
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York 10027, USA
* e-mail: ss2735@
Published online: 30 May 2008; doi:10.1038/nmat2203
Microscale fabrication of three-dimensional (3D) extracellular Nevertheless, micropatterning and integration of diverse 3D
matrices (ECMs) can be used to mimic the often inhomogeneous natural ECM materials remains technically challenging because:
and anisotropic properties of native tissues1–3 and to construct (1) the microfabrication technique must accommodate diverse
in vitro cellular microenvironments4–6 . Cellular contraction mechanisms for the gelling of natural ECM (such as temperature
of fibrous natural ECMs (such as fibrin and collagen I) can change or enzymatic action); (2) established techniques for
detach matrices from their surroundings and destroy intended patterning 3D ECM (ref. 19) require ranges of viscosity and
geometry7–9 . Here, we demonstrate in situ collagen fibre assembly conductivity that are incompatible with important natural ECMs
(the nucleation and growth of new collagen fibres from (such as collagen or Matrigel); (3) rapid contraction of natural
preformed collagen fibres at an interface) to anchor together ECM by cells7,9 can destroy intended ECM geometry and
multiple phases of cell-seeded 3D hydrogel-based matrices disintegrate interfaces among multiple ECM phases.
against cellular contractile forces. We apply this technique t
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