Biomedical Engineering Reference
In-Depth Information
an overall 3D construct. After one layer is fabricated, it is often stabilized before the next layer is
printed to provide a flat new printing surface. For LbL LDW, liquid hydrogel, or hydrogel precursor
suspending a desired biologic, is used as a transfer material, similar to the 2D printing method. The
hydrogel is deposited at preprogrammed coordinates, according to the specific layer design. Once
the printed layer is completed, it is gelled by either cross-linking the polymer solution, or inducing
polymerization. Gelation can be triggered by a number of different cross-linking or polymerization
mechanisms (e.g. thermal, ionic, pH, or enzymatic), depending on the hydrogel or hydrogel blend.
The rate of gelation for each of these mechanisms differs, and generally a fast gelation time is desired
to maintain pattern fidelity. Once the layer is gelled, the printing surface is stabilized, and the process
can be repeated to add additional layers until the overall construct is completed.
Another method of performing LbL fabrication with LDW utilizes a hydrogel precoated on the
substrate, rather than in the transferred material. Thin-film coating mechanisms can consistently make
thin layers of liquid hydrogel polymer or precursor on a substrate at a desired height. The selected
material is transferred into the liquid hydrogel layer in a programmed pattern. The layer is gelled,
and a new printing layer is produced by the addition of new hydrogel solution, again coated to the de-
sired layer thickness. This technique is very similar to the previous method, but may hold advantages
if each layer needs only a small amount of printed substance, relative to the overall bulk material.
These techniques can be repeated for a desired number of layers. 3D resolution is determined by the
hydrogel coating mechanism's control over the height of the newly laid hydrogel layer. The average
height for individual layers with one such coating technique, blade-coating, approaches approximately
40
m
m (
Gruene et al., 2011b
). Combinations of hydrogel materials previously used in LbL LDW, as
well as other candidate materials, have been listed in
Figure 5.3
. LbL LDW has been used for
in vitro
and
in vivo
skin tissue, an osteosarcoma model, and cardiac regeneration (
Koch et al., 2012; Gaebel
et al., 2011; Catros et al., 2011
). Beyond creating tissue models, 3D LDW can be used to study cell-
to-cell signaling. One powerful example of 3D LDW studied the coculture signaling and migration
between adipose-derived stem cells and endothelial colony forming cells in hyaluronic acid and fibrin
gelsu (
Gruene et al., 2011a
).
The LbL LDW printing technique appears to be very similar to another LbL technique, ink-jet
printing, which has also been adapted for biological applications. Ink-jet printing deposits hydrogel
material, which suspends cells, directly from a nozzle to a substrate, either spot by spot or by con-
tinuous flow. Discrete layers of printed material are often gelled prior to printing additional layers.
The advantages of ink-jet printing include that it is generally less expensive than LDW, and offers
higher throughput.
5.4.3
LDW MICROBEADS
Microbeads are spheroidal microstructures that can encapsulate a desired biologic, and have
been investigated for applications ranging from drug delivery to cell culture (
Xie et al., 2009;
Amsden et al., 1997
). For cell-based applications, microbeads are fabricated from cross-linkable
polymers, or precursor as used for hydrogels. Like bulk hydrogels, microbeads provide cells with a
3D environment, but there are distinct advantages to the microbead structure. Nutrient diffusion into
bulk hydrogels occurs slowly, and large gels may even require a bioreactor to prevent encapsulated
cells from suffering from ischemic effects or buildup of metabolic waste. Microbeads, on the other
hand, have a high surface area-to-volume ratio, allowing for more rapid exchange of nutrients and
Search WWH ::
Custom Search