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Zhu et al. HA in tissue engineering

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Figure 2: The morphology of hyaluronic acid (RESTYLANE ) using Figure 3: The gross view of cross-linked hyaluronic acid using
scanning electron microscopy BDDE at the concentration of 0.8%
alcohols and aryl fatty alcohols can be bound to HA withstand greater mechanical force [19] .
moleculesin order to improve the chemical properties
of HA and its stability as a tissue engineering scaffold, It is almost certain that most kinds of vertebrate cells
as well as to extend its maintenance in the human body. synthesize HA at some point in their natural history.
The purpose of HA cross-linking is to convert it from When fibroblasts, mesothelial or certain other kinds
solid state to hydrogel state under mild conditions and of cell are plated out in tissue culture, they surround
to prolong its maintaining time in the human body [17] . themselves in a few hours with a transparent gel-like
Besides, the mechanical strength of crosslinked HA HA which can protect themselves against damage
can be remarkably improved compared to the non- by immune cells, impedes virus infection and may be
crosslinked one, which makes it more suitable for important in mitosis [19] .
tissue engineering applications.
CELL-MATRIX INTERACTIONS IN HA
The cross-linking reaction of HA can be divided HYDROGEL SCAFFOLDS
into complete or incomplete one. The complete
cross-linking reaction causes the HA molecules to
be covalently attached to the continuous polymer At present, different origins derived stem cells are the
network so that HA is no longer soluble in the water. most universally used seed cells in tissue engineering.
While the incomplete reaction prompts part of the HA can interact with many stem cell surface receptors,
covalent binding reactions of HA molecules, resulting inducing intracellular signal transduction through
in partial solubility after the reaction. 1-ethyl-3-(3- the connection with these receptors and activating
dimethylaminopropyl) carbodiimide, divinyl sulfone, corresponding proteins in a direct or indirect pattern [20] .
glutaraldehyde, butanediol-diglycidyl ether are the
most common crosslinking agents [Figure 3] [18] . Through signal transduction receptors, HA can
affect the most essential cell activities including
The biological property of HA proliferation, survival, movement and differentiation.
HA is synthesized by HA synthesis (HAS) on the cell One of the most important receptors is CD44, which
membrane. And it is the only glycosaminoglycan provides an agent for maintaining and anchoring the
that is not synthesized in the Golgisome. There are proteoglycan polymer to the cytoplasmic membrane.
three different HAS in mammals, HAS1, HAS2 and CD44 plays an important role in tissue formation
HAS3. The three enzymes are located on different by mediating the remodeling of extracellular
chromosomes, producing HA with different molecular matrix, intercellular interactions, and cell-matrix
weights [11] . The expression of HAS isoenzymes interactions [21] . In addition, the close connection with
varies under different status of morphogenesis and the cytoskeleton allows CD44 to induce intracellular
pathology. For example, HA in infants is of abundant signal transduction, thereby experiencing changes in
quantity, however, in the process of growing up it is the extracellular matrix environment and triggering
gradually replaced by collagen fibers and proteolycins cellular responses [22] . Besides, CD44 receptors are
which accounts for the fact that mature tissue can of widespread concern because they are essential to

Plastic and Aesthetic Research ¦ Volume 4 ¦ December 29, 2017 221