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Zhu et al. HA in tissue engineering
[5]
maintain cartilage phenotype and HA catabolism . used in a variety of fields. The ideal tissue engineering
HA-containing materials can also interact with proteins scaffold should have good cell adhesion to support the
or cells through the receptor for hyaluron-mediated growth of seed cells, however, HA tends to have weak
motility or intercellular adhesion molecule-1. cell adhesion. Therefore, modifications like heparin
decorated, Arg-Gly-Asp (RGD) sequence linking are
There are also some reports that HA-based indispensable [29-31] .
scaffolds can directly induce or promote stem cell
differentiation [22] . In vitro experiments conducted by HA in vascular tissue engineering
Meng et al. [23] demonstrated that HA-based scaffold In tissue engineering construction, a scaffold has to
can induce stem cells into cartilage in basal medium maintain its structure for several months or longer
without the addition of growth factors. The increased before extracellular matrix is deposited. Since the
expression of an important HA receptor like CD44, diffusion of nutrients and essential gases to cells
also suggested the interaction of cells with HA [24] . In is typically limited to a depth of 150-250 μm from a
addition, Choi et al. [25] reported that HA oligomers capillary (3-10 cells thick) [32] , tissue constructs must
in the skin substitute models could promote the permit in-growth of a blood capillary network to
survival of basal stem cells. Their experiments nourish and sustain the viability of cells within . HA
[4]
demonstrated that a recognized skin stem cell can be chemically modified to promote angiogenesis
marker p63 expression was elevated in the skin without changing its original biocompatibility or
substitute model added HA oligomer (400-2000 Da), weak immunogenicity [33] . HA can be degraded into
therefore, HA may also help to maintain stemness [25] . oligomers (HA oligomers, HAO) (4-25 dose units)
Huang et al. [26] also reported that mesenchymal stem by hyaluronidase in vivo. These HAOs have a high
cells grown on chitosan-HA membranes performed biological activity and are capable of affecting
better in maintaining stemness markers (Oct4, Sox2 cell behavior including angiogenesis through
and Nanog) than cells cultured on common dishes. monovalent bond to the host cells [3,34] . Silva et al.
[2]
On the contrary, if CD44 was blocked by the antibody, demonstrated that gellan gum-HA hydrogel can be
then the cells would lose their ability to maintain the degraded by hyaluronidase and release various
spherical form while the stemness gene expression amounts and sizes of HA oligomers that are capable
would also decline. It indicated that HA may assist in of promoting the proliferation of human umbilical
maintaining stemness through CD44 [26] . vein endothelial cells.Besides, in the mice hind limb
ischemia model, HA-cell composite can significantly
HAIN TISSUE ENGINEERING promote angiogenesis. A series of in vitro and in vivo
experiments have shown that long-chain (native high
Tissue transplantation is one of the most frequent and molecular weight) HA at physiological concentrations
most important treatments in plastic and reconstructive has the ability to resist inflammation and inhibit
surgery. However, autologous transplantation is often angiogenesis. Long-chain HA can bind to CD44, and
limited by the insufficiency and trauma of donor site, inhibit cell proliferation, cell cycle in the key signal
while allogeneic transplantation is faced with immune transduction, thereby inhibiting angiogenesis.While
rejection, donor scarcity, transplant infection and HAO will compete with long-chain HA for binding
other risks. The emergence of tissue engineering is to CD44 and prompt mitosis and angiogenesis [35] .
a promising technique to overcome these problems The CD44-HA oligosaccharide interactions that
above. primarily cause these pro-mitotic effects have also
been shown to stimulate matrix metalloproteinase-2
Tissues or even organs can be regenerated by and -9 production and thereby increase cell invasion
the coordination of seed cells, scaffold and growth through extracellular matrix barriers to facilitate vessel
factors. The histocompatibility, chemical modification sprouting and outgrowth [36] . Since the pro-angiogenic
and biodegradability of HA make it an ideal scaffold HA oligomers cannot by themselves be crosslinked to
for tissue engineering. The properties of hydrogel yield solid biomaterials, and can also potentially incite
can mimic the water content of human tissue and inflammatory/activated cell responses, they must be
contribute to the exchange of oxygen, nutrition and presented on other scaffolding biomaterials, either
metabolic waste [27,28] . In addition, the fluid morphology synthetic or natural [37,38] . Another method is to mix with
makes it possible to inject the scaffold through a tiny the more bioinert long-chain HA in such a manner as
needle hole, which can greatly reduce the trauma and to fulfill the physical and mechanical requirements of
infection rate of the operation. Therefore, it has been the biomaterial, elicit the desired biologic responses,
[4]
one of the hotspots in tissue engineering materials and and yet deter excessive and long-term inflammation .

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