BIOMATERIALS FOR BIOPRINTING - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 136

FIGURE 6.3
Chemical structure of hyaluronic acid.
inversely proportional to the degree of crystallinity. Its degraded product includes chitosan with
lower molecular weight, N -acetyl-D-glucosamine residues, and chitogligomers ( Ren et al., 2005 ).
6.4.1.6 Hyaluronic acid
Hyaluronic acid (HA) is a linear polysaccharide consisting of a repeating disaccharide of (1-3) and
(1-4)-linked b -D-glucuronic acid, and N -acetyl- b -D-glucosamine units (Alberts et al., 1994 ). The mo-
lecular structure is shown in Figure 6.3 . It is a highly hydrated polyanionic macromolecule ( Khan
and Ahmad, 2013 ) and can be found in almost every mammalian tissue and fluid. It has been widely
used in wound healing and the synovial fluid of joints. A number of methods can be used to form HA
hydrogels, such as covalent cross-linking with hydrazide derivatives, polyfunctional epoxides, car-
bodiimides, self-crosslink, and esterification ( Collins and Birkinshaw, 2013 ). The reactive groups of
HA (-OH and -NHCOCH 3 ) provides cross-linking sites for hydrogel formation or can be modified
for enhanced properties ( Khan and Ahmad, 2013 ). HA is naturally degraded by hyaluronidase, which
allows cells to regulate the clearance of the material locally.
6.4.2 SYNTHETIC HYDROGELS
Synthetic hydrogels are some of the earliest biomaterials used as scaffolds in tissue engineering. The
natural hydrogels presented in Section 4.1.1 are becoming increasingly popular due to their inherent
biocompatibility. Comparatively, synthetic hydrogels have shown their benefits (e.g. highly tunable and
consistent properties, and large-scale production capacity) in the field of regenerative medicine. This
subsection presents three of the most commonly used synthetic hydrogels.
6.4.2.1 Poly(2-hydroxethyl methacrylate)
Poly(2-hydroxethyl methacrylate) (PHEMA) hydrogels have been used as implant materials since the late
1960s. They are synthesized using free radical precipitation polymerization of 2-hydroxyethyl methac-
rylate ( Slaughter et al., 2009 ). The resultant hydrogel is biologically inert but relatively weak. It is also a
highly resistant material to protein adsorption and cell adhesion. However, it has been found that PHEMA
implants undergo delayed, episodic calcification in vivo (Belkas et al., 2005 ). PHEMA is a neutrally
charged gel and the molecular structure of neutrally charged PHEMA repeat units is shown in Figure 6.4 .