Biomedical Engineering Reference
In-Depth Information
tissues, we have incorporated the use of non-invasive electrical stimulus to charac-
terize and control the human fi broblast adhesion and movement in the 3D collagen
gel model (Sun et al.
2004
). The cell movements in the 3D collagen gel were shown
to depend on both electrical stimulus strength and collagen concentration. A small
non-invasive electrical stimulus (0.1 V/cm) was found to be suffi cient to induce 3D
cell migration, while the collagen concentration of ~0.6 mg/ml appeared to repre-
sent the optimal scaffold network environment. However, the same electrical stimu-
lus failed to induce 2D cell movement. This observation provides a clue that
biophysically unconstrained 2D cell adhesion may represent the “exaggerated state”
of cell adhesion, and that the suffi cient and necessary cell adhesion found in the 3D
collagen gel, which resembles in vivo cellular responses, is likely weaker than that
found on 2D substrate. It is interesting to note that this induced human fi broblast
movement in 3D collagen gel is both integrin- and Ca
2+
dependent (Sun and Cho
2004
). Treatment of cells with anti-integrin antibodies prevents electrically induced
cell movement. While the absence of extracellular Ca
2+
suppresses the 3D cell
movement, inhibition of the cell-surface receptor-coupled phospholipase C (PLC)
completely prevents 3D cell migration, suggesting molecular association among
integrin, PLC, and intracellular Ca
2+
. Elucidation of the electrocoupling molecular
mechanisms involved 3D cell movement could lead to controlled and designed
manipulation of 3D cell adhesion and migration, and may be used to complement
the microfabrication techniques that have been successfully applied to tissue
engineering.
4.2
Nanofabrication
Recent progress in nanotechnology provides a variety of methods for fabricating
materials with nanostructure and nanochemistry similar to that naturally occurring
in the cell surrounding. Both micro- or nanoengineering techniques are aimed to
control physicochemical and biological properties of synthetic materials, which are
thought to be essential for guiding complex cellular processes and directing cell
behavior and functions (Curtis
2004
; Lutolf and Hubbell
2005
) . These nanoscale
features include, but not limited to distribution of receptor-binding ligands and sur-
face-bound growth factors, surface nanotopography, presentation of domains sus-
ceptible for cell-triggered degradation, and remodeling. Molecular mechanisms
found in the natural ECM that regulate cellular functions are being incorporated in
fabrication of synthetic extracellular environment at nanoscale. For example, mount-
ing data support the notion that cells respond to the precise nanoscale spatial
organization of adhesion ligands (Irvine et al.
2002
). This is perhaps related to the
intrinsic adhesion protein (e.g., integrin) properties to cluster in order to form
focal adhesion contacts and mediate appropriate cellular responses. While ran-
domly distributed adhesion ligands appear to support cell attachment, neither full
cell spreading nor haptokinetic or chemokinetic motility was observed. Moreover,
the size of ligand cluster controls strength of cell-substratum adhesion, cytoskeleton
