Biomedical Engineering Reference
In-Depth Information
tissues must have a prearranged spatial architecture in order to function correctly, much attention
has shifted to designer scaffolds. This hypothesis is based on the fact that a large number of organs
possess a well-defi ned internal structure, which is essential to their function. Thus, in order to
realize 3-D constructs for tissue repair and reconstruction, it is necessary to guide cell growth on
structures with an established topology, which replicates that of natural tissue. As a result, several
different microfabrication techniques for biomaterial scaffolds have been developed. Most of these
techniques arise from preexisting manufacturing methodologies such as photolithography, silicon
micromachining, and the realization of pseudomechanical microcomponents. We can distinguish
two groups of methodologies: one based on the realization of two-dimensional (2-D) structures and
the other on the fabrication of 3-D scaffolds. In this chapter, we focus exclusively on 3-D methods
borrowed from the well-established fi eld of computer-aided design/computer-aided manufacturing
(CAD/CAM) and rapid prototyping (RP).
4.2 MICROFABRICATION OF THREE-DIMENSIONAL
STRUCTURES: RAPID PROTOTYPING
RP, which is synonymous with solid free-from fabrication (SFF), refers to the fabrication of 2-D
or 3-D structures using a preprogrammed computer graphics fi le containing layer-by-layer maps of
the structures. Figure 4.1 schematizes this structure in terms of the liver, one of the most complex
organs in the body. These maps are reconstructed through computer-aided fabrication (usually an
x-
,
y-
,
z
-positioning system), much as a 3-D printer would do. Each layer is about 0.01-1 mm thick
(this depends very much on the manufacturing process as well as the resolution required), and a
3-D object is built-up through the assembly of successive 2-D layers, or what we call a pseudo-
3-D (PS3D), sometimes also known as 2½ D. Nowadays RP is the chosen method of production
for manufacturing complex objects, surpassing traditional techniques such as milling and turning.
However, it should be noted that rapid is a relative term, and it usually takes several minutes to
several hours to produce an object.
The RP process can be subdivided into three main units:
•
•
•
Generation and conversion of the CAD model
Realization of the prototype
Postprocessing
In the fi rst phase, a 3-D object is decomposed into a stratifi ed structure using appropriate soft-
ware, such as AutoCAD. The layers are then codifi ed into step-by-step instructions for the control
system, which drives the
x-
,
y-
,
z
-positioner. Currently, RP for tissue engineering scaffolds is associ-
ated with the use of CAD design fi les originating from computerized tomography (CT) data. Their
most appropriate application is in the bone tissue engineering, where high-resolution micro-CT
can reveal structural features of the order of 5 µm. In the case of soft tissues, architecture is not
only harder to defi ne, but also more diffi cult to image with high resolution, because information on
structure is reconstructed largely from histological specimens. Conversion of histological images
into a layer-by-layer and step-by-step scaffold is hindered by the lack of contrast and nonspecifi city
of stains (such as eosin and hematoxylin). It is very diffi cult to identify cell contours and separate
them from the contents of the extracellular matrix (ECM). Soft-tissue scaffolds are therefore gener-
ally constructed with a repetitive grid consisting of squares, triangles, or hexagons. In fact, one of
the most challenging aspects of scaffold design for nonbony biological tissues is the extraction of
structural features, and the conversion of these into a repetitive algorithm describing an appropriate
locus of points or lines in a given plane.
Once the architecture has been chosen, the three-axis positioners proceed to the actual fabrica-
tion of the structure, following the location maps provided by the controller. This process can be
quite complicated, since binders, powders, and fi llers are usually involved.
