Biomedical Engineering Reference
In-Depth Information
Table 9.6
Classification of the most frequently applied hydrogel solidification mechanisms in RP
processing
Types of hydrogel solidification
in RP systems
After scaffold fabrication
During scaffold fabrication
Forming physical
hydrogels
Forming chemical
hydrogels
Post-fabrication treatment
Precipitation
Liquid-solid phase
transition
- agar;
- Pluronic* F127;
- ...
Reaction in the
hydrogel
- PEGDA;
- hyaluronan meth-
acrylate;
- ...
Reaction with
a medium
- fibronectin +
thrombin;
- gelatin + EDC
- ...
- infiltration
- forming chemical
hydrogels after the
formation of a physical
network
- reaction with a medium
(e.g. sodium alginate in
CaCl
2
-solution)
- chitosan solution;
- collagen dispersion;
- ...
tissue regeneration requires strengths of 10-1,500 MPa, while soft tissue strengths
are typically located between 0.4 and 350 MPa [
244
]. As a part of it, preserving the
mechanical integrity of the scaffold contributes substantially to the completion of
this demand. The latter appears to be of utmost importance with respect to hydro-
gels and will for that reason be discussed in this subsection. Moreover, it is possible
to enhance the control over not only the mechanical properties, but even the biologi-
cal effects and degradation kinetics by hierarchical design of scaffolds with micron
to millimetre features [
233
]. In the case of hydrogel performance, degradation rates
are controlled by hydrolysis, enzymatic reactions or simply by dissolution of the
matrix (e.g. ion exchange in Ca
2+
crosslinked alginate systems).
The process of obtaining a construct with suitable strength starts with the
solidification and simultaneous shaping of the material in a certain pattern. An over-
view summarizing the most frequently applied and different solidification mecha-
nisms is given in Table
9.6
. Although our discussion focuses on hydrogel materials,
other materials could easily be incorporated into this scheme.
The application of natural as well as synthetic hydrogels in TE and as cell embed-
ding materials has been a review topic of several authors [
11,
25,
32,
65
] . The
solidification or gelling mechanisms of hydrogels include inherent phase transition
behaviour and crosslinking (ionic or covalent) approaches. Regarding the former
mechanism, careful control over the printing temperatures can provide for some
hydrogels a phase transition from solution to gel state, in particular for polymers with
a lower critical solution temperature (LCST) behaviour (e.g. Pluronic
®
F127).
However, this behaviour is reversible. The formation of an ionically crosslinked net-
work through the use of multivalent counterions, e.g. sodium alginate and Ca
2+
ions,
provides more control over the mechanical integrity. Nevertheless, these ions could be
leached out in long-term culture, or even be exchanged by other ionic molecules,
compromising the control over the construct properties. Therefore, in most cases,
covalent network formation is required in order to precisely enhance the mechanical
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