Biomedical Engineering Reference
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stream. Together, these inherent biocompatibility, biodegradability and
non-immunogenicity properties, make HA an attractive natural material
for the construction of hydrogels in tissue remodelling, especially in the
nervous system.
1.2.2 Construction of Hyaluronic Acid Hydrogel for
Mimicking Extracellular Matrix
To design a good hydrogel scaffold, the formation of the crosslinked
network is the most important step because many important properties
such as swelling, mechanical properties and degradation are closely
linked to this structure. For the construction of hydrogels, HA is usually
fabricated by chemical techniques, using many small molecules as the
crosslinkers, such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
(EDC), adipic acid hydrazide(ADH) and divinyl sulfone [19]. The
crosslinkers fabricate the liner polymers of HA into a stable porous
structure, like a sponge, which has a high water content. This typical
structure is presented in the observation by Tian and co-workers
with scanning electron microscopy (SEM) (
Figure 1.1
), in which the
hydrogel of HA with polylysine is crosslinked by ADH and EDC in
the ratio of 10:1 (w/w, HA: polylysine) [20]. Several authors have
reported that the elastic modulus of this HA hydrogel shows it to
be a soft gel [20-22] , and it usually exhibits the typical features of
a weak gel, with similar viscoelasticity, architecture and stiffness to
that of the brain or spinal cord tissue [23, 24]. In addition to these
desired physical properties, as a natural material in ECM, the HA
gels possess good degradability by hyaluronidase and then break into
oligosaccharide fragments, as reported by Shu and co-workers [25].
Also, Goodison and co-workers [26] have reported that HA gels
have good compatibility with tissue and cells, providing an effective
support to the survival, spreading, growth and even differentiation
of cells, through interacting with cell receptors and then influencing
signalling pathways in the cells. Furthermore, there have been studies
reporting that the HA gel readily forms secondary constructions
by means of various physical entrapments of particles or chemical
integration of biological molecules [27-30]. Modified HA hydrogels
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