BIOMATERIALS FOR BIOPRINTING - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 131

6.3.1.1 Ionic Cross-linking
Ionic hydrogel is one of the most commonly used physical hydrogel. It has a reversible characteristic
that helps to ensure consistent viscosity during printing. Moreover, it has excellent cytocompatibility
since no other chemicals are used. These interactions can be between oppositely charged polyelectro-
lytes or between polyelectrolytes and charged molecules. The length of the polymers and their charges
determine the strength of the ionic interactions. However, due to its simplicity in cross-linking interac-
tions, its construct is also mechanically weak.
6.3.1.2 Thermal Cross-linking
Thermo-sensitive gelation and cross-linking is triggered by interactions between polymer chains in the
solution. These interactions are usually reversible and form cross-linked polymers at low temperatures,
but viscous solutions above a specific temperature. This behavior can be commonly seen in many natu-
rally occurring, water-soluble polymers, such as gelatin and carrageenan.
However, researchers have developed a reverse thermal behavior hydrogel that forms a gel at higher
temperatures but melts at lower temperatures ( Yoshioka et al., 1994 ). This mechanism of gelation is
related to the temperature dependency of polymer-solvent interaction and a heterogenous polymer
microstructure. Part of the chain becomes more hydrophobic at higher temperatures, inducing a local
cross-linking, and consequently, a gelation process. Some of the common hydrogels that participate in
such behaviors are methylcellulose and Poly( N -isopropylacrylamide) hydrogels.
6.3.1.3 Stereocomplex Cross-linking
Stereocomplex formation of hydrogel occurs between polymers of opposite chirality, interactive with
one another ( Hennink et al., 2004 ). They have similar characteristics in terms of properties and advan-
tages as ionic cross-linked hydrogel. These hydrogels usually take longer to stabilize.
6.3.2 CHEMICAL
Chemically cross-linked hydrogels are formed by chemically binding the chains of polymer with one
another. These polymers are permanent and can be generated by covalently cross-linking hydrophilic
polymers or converting hydrophobic polymers into hydrophilic polymers. Since these hydrogels' for-
mation is permanent, dispensing of such materials is usually done before cross-linking reaction has
occurred.
6.3.2.1 Free Radical Polymerization
Free radical polymerization is one of the most frequently used techniques in bioprinting to cre-
ate chemically cross-linked hydrogels. Polymer with vinyl groups are usually polymerized to
form hydrogel using redox reaction or through the use of thermal or photo-initiator. The photo-
initiators used are wavelength-specific and must meet a minimum energy level before reaction
can occur. These reactions are usually fast and the gels are usually permanently cross-linked.
However, UV light exposed to cells has to be controlled as the UV radiation may cause cellular
necrosis due to the heat released during curing. Long exposure time may also cause damage and
mutations in the DNA of the cells, leading to long-term damage to cellular metabolic activity.
Thus, the intensity of the UV light is usually limited to between 5 and 10 mW/cm 2 to prevent such
occurrence ( Cho et al., 2009 ).