BIOMATERIALS FOR BIOPRINTING - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 130

6.2.8 DEGRADATION
The degradation rate of a material is usually matched with the rate of tissue regeneration ( Dhanda-
yuthapani, 2011 ). This is to ensure that the scaffold can still provide the necessary support for cells to
regenerate completely. If the degradation rate is too short, the hydrogel support may be encapsulated
by fibrous tissue when implanted into the body, blocking the overall cellular regeneration. If the deg-
radation rate is too long, chronic inflammatory response may set in, which in turn will cause greater
damage to the body.
Unlike solid polymers, hydrogels undergo purely bulk degradation since they are hydrated within the
structures. To control the degradation of these polymers, researchers have come up with hydrogels that
have been copolymerized with peptides sensitive to enzymatic degradation ( Drury and Mooney, 2003 ).
One such research by Lei controlled the degradation with the use of polyethylene glycol (PEG) hydro-
gel that incorporates with matrix metalloproteinase (MMP) sensitive peptides ( Lei et al., 2010 ). These
peptides respond to local protease activity on the cell surface and degrade accordingly.
Determination of these changes in degradation can be characterized by observing changes in their
weight, elastic modulus, and swelling degree with respect to their initial condition. The hydrolysis and
enzymatic degradation of the hydrogel polymers reduce the efficiency of the cross-linking mechanism
in the gel thus reducing the above properties of the gel ( Lee et al ., 2004 ).
6.3 HYDROGEL CROSS-LINKING MECHANISM
In general, all biomaterials used for bioprinting are made of cross-linking mechanisms that can be
categorized as either physical or chemical. The type of cross-linking initiated on the hydrogel will
yield either a reversible or a permanent gel, which in turn will affect the printing process. Perma-
nent hydrogels created by chemical cross-linking require postcuring, but have higher mechanical
strength compared to their physically cross-linked counterparts. The different cross-linking mecha-
nisms also determine the mechanical strength of the scaffold and the compatibility of the cells with
the hydrogel.
In the cross-linked state, hydrogels can attain an equilibrium swelling in aqueous solutions depend-
ing on the cross-linking density. These hydrogels are also not homogenous ( Drumheller and Hub-
bell, 1995 ). They have regions of low water swelling clusters that are dispersed within the regions of
high swelling clusters. This may be caused by hydrophobic aggregation of cross-linking molecules
leading to higher cross-linking density clusters within the region. Phase separation and formation of
water-filled voids can occur in some circumstances during gel formation, depending on the solvent
composition, temperature, and solid concentration used.
6.3.1 PHYSICAL
Physically cross-linked hydrogels are formed by molecular entanglements, and other secondary
forces such as ionic, hydrogen bonding, and hydrophobic forces ( Campoccia et al., 1998 ). They are
mostly reversible; however, they cannot easily become homogenous as the clusters of molecular
entanglements, or hydrophobic and ionic domains found within the polymer chains, are nonhomog-
enous ( Hoffman, 2002 ). These free chain ends or chain loops create a temporary network defect
within the gels.