Biomedical Engineering Reference
In-Depth Information
9.5
Fundamentals on Rapid Prototyping in Scaffold-Free
Tissue Engineering
In general, the application of scaffolds in a TE approach is straightforward, but
still subject to some challenges [
266,
267
]. These can be divided in two distinct
categories: (1) complications posed by host acceptance (immunogenicity,
inflammatory response, mechanical mismatch) and (2) problems related to cell
cultures (cell density, multiple cell types, specific localization). It is surprisingly
interesting that, during embryonic maturation, tissues and organs are formed
without the need for any solid scaffolds [
268
]. The formation of a final pattern or
structure without externally applied interventions, in other words the autonomous
organization of components, is called self-assembly [
269,
270
] . A premise con-
cerning the self-assembly and self-organizing capabilities of cells and tissues is
worked out in the field of scaffold-free TE. This idea poses an answer to the
immunogenic reactions and other unforeseen complications elicited through the
use of scaffolds. One way of implementing this self-assembly concept is the use
of cell sheet technology, which was demonstrated by L'Heureux and colleagues
for the fabrication of vascular grafts [
271,
272
]. In a similar way, the group of
Okano engineered long-lasting cardiac tissue based on cell sheet strategies [
273-
275
]. Remarkably, some have already reached clinical trials [
275,
276
] . An alter-
nate approach was selected by McGuigan and Sefton [
33
] , who encapsulated
HepG2 cells in cylindrical sub-millimetre gelatin modules, followed by endothe-
lializing the surfaces. A construct with interconnected channels that enabled per-
fusion was generated through random self-assembly of the cell/hydrogel modules.
However, the implementation of RP technologies offers another even more fasci-
nating perspective on scaffold-free TE, and is commonly termed “bioprinting” or
“organ printing”.
We define organ printing as the engineering of three-dimensional living struc-
tures supported by the self-assembly and self-organizing capabilities of cells deliv-
ered through the application of RP techniques based on either laser [
277-
280
] ,
inkjet [
218,
227,
229,
235,
281-
286
] , or extrusion/deposition [
191,
195,
287-
292
]
technology. An emerging laser-based RP technique called biological laser printing
(BioLP) stems from an improved matrix assisted pulsed laser evaporation direct
write (MAPLE DW) system. The improvement is realized by incorporation of a
laser absorption layer and thus eliminating the direct interaction with the biological
materials. The principle is illustrated in Fig.
9.9
. Prior to laser exposure, a cell sus-
pension layer is formed on top of the absorption layer. Then, a laser beam is focused
on the interface of the target, which causes a thermal and/or photomechanical ejec-
tion of the cell suspension towards the substrate [
277
]. Target and substrate are both
able to move in the planar field.
The workflow of inkjet- or extrusion-based bioprinting can be represented by
Fig.
9.10
. In short, balls of bio-ink are deposited in well-defined topological patterns
into bio-paper sheets. The bio-ink building blocks typically have a spherical or cylin-
drical shape, and consist of single or multiple cell types. Several bio-ink preparation
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