Biomedical Engineering Reference
In-Depth Information
Sciperio Inc. (www.sciperio.com) claims to be developing a new
in vivo
direct-deposition
machine for the fabrication of
in vivo
tissue using advanced minimally invasive techniques, vision
and diagnostic imaging systems, biological sensing systems, ultrashort-pulse-laser tissue ablation,
and the fabrication and assembly of 3-D tissue constructs. The system described is essentially a
dream tissue engineering factory, which has been envisaged by several researchers. According to
Sciperio, the tool will be able to deposit a wide variety of cells (e.g., stem cells, endothelial cells,
chondrocytes, T-cells, dendritic cells), growth factors, nutrients, ECM proteins, and biocompatible
structural materials with exquisite precision.
Envisiontec (www.envisiontec.de) has developed the bioplotter technology, invented at the
Freiburg Materials Research Centre in 1999. The system is based on a 3-D dispenser and allows
processing a magnitude of materials including various biochemical systems and even living cells.
CAD data handling and machine/process control are done through a system-specifi c pseudo-3-D
CAD/CAM software. The bioplotter principle is based on dispensing a plotting material into a
plotting medium to cause solidifi cation of the material and to compensate gravity force through
buoyancy. In the presence of a temperature-controlled plotting medium, the solidifi cation of the
material during plotting into the medium can be modulated by precipitation reactions, phase transi-
tions, or chemical reactions. The bioplotter is the only commercial RP system available at fairly
reasonable cost.
Neatco and Dimarix (www.dimatix.com) have created a cartridge-style printhead that allows
users to fi ll their own ll uids and print immediately with different materials. For the moment the sys-
tems are still used for liquid printing DNA arrays or sensors, but they can potentially be employed
for organ printing. Each single-use cartridge has 16 nozzles linearly spaced at 254 µm with a typical
drop size of 10 pL and can be replaced to facilitate printing of a series of fl uids.
There is no doubt that in future the number of scaffolds available on the market will increase
steadily. It should, however, be kept in mind that the road ahead to the real medical applications of
RP scaffolds is still long and arduous. An emerging critical factor that should be considered in all
design and processing phases is the application of good manufacturing practice (GMP) principles
and standards to RP methods and products for biomedical use. Scaffolds should be considered as
biomedical devices for advanced therapeutics, and RP technologies are therefore a key part of the
manufacturing and validation processes.
4.10 DISCUSSION: LIMITATIONS AND CRITIQUES
In this review, we have given a general description of the state of the art of RP methods for the reali-
zation of scaffolds for tissue engineering applications. There is no doubt that the microstructural
environment of a cell conditions its behavior, and scaffold-based tissue engineering is founded on
this very principle. However, as yet we do not have any rules or guidelines on just what this micro-
structure should be and in general very little effort has been made toward defi ning structural design
parameters. Until we establish architectural canons for biological tissue, the main advantage of RP
technologies over other material processing methods is their ability to generate reproducible and
repetitive structures with controlled porosity, which do not vary from batch to batch and at present
adhering to an industrial rather than biological requirement.
As summarized in Table 4.1, it is clear that a large variety of RP techniques exist, and the choice
of one method with respect to another depends on manufacturing effi ciency and the desired resolu-
tion as well as on the polymer chosen for fabrication; there is no optimal or unique RP method. Each
RP technique must be matched with a particular organ considering cell density, cell size, organiza-
tional and nutritional requirements, as well as mechanical matching between scaffold and tissue.
It can also be argued that RP fi ts the tissue engineering paradigm better than the classical
subtractive fabrication methods such as milling or turning. In RP the object or prototype is created
through an additive process not dissimilar to the process of biological development in which cells
