Design and Synthesis of Photoreactive Polymers for Biomedical Applications - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 256

ratio was measured using micropatterning on the titanium substrate [31].
The resultant titanium surface was found to be effi cient in EGF immobili-
zation and in enhancement of cell growth.
11.2.2 Polysaccharides
11.2.2.1 HyaluronicAcid
Hyaluronic acid (HA) is a linear polysaccharide of (1- b -4) D-glucuronic
acid and (1- b -3) N -acetyl-D-glucosamine. It is an anionic, usually nonsul-
fated glycosaminoglycan distributed widely throughout connective, epi-
thelial, and neural tissues. Its molecular weight often reaches the millions.
One of the chief components of the extracellular matrix, HA contributes
signifi cantly to cell proliferation and migration and might also be involved
in the progression of some malignant tumors. Artifi cially sulfated HA was
coupled with azidophenyl groups and the UV-reactive hyaluronic acid
was employed to construct an antithrombogenic surface [32]. In addition,
it is known that the level of HA regulates gene expression, signaling, pro-
liferation, motility, adhesion, metastasis, and morphogenesis of embry-
onic stem (ES) cells in vivo . In humans, the HA content in vivo is greatest
in undifferentiated ES cells and during early embryogenesis. Therefore,
HA is being used widely to culture and propagate stem cells, and the fab-
rication of biodegradable three-dimensional HA scaffolds enriched with
multipotent stem cells seems to be a promising strategy for the repair of
irreversibly injured tissues. HA scaffolds support the undifferentiated
proliferation of ES cells in the absence of feeder cell layers and retain their
ability to differentiate after release from HA hydrogels. Moreover, it is
known that the effect of HA on the cellular environment varies according
to its molecular weight (MW). For example, it is generally accepted that
low-MW HA (LMW-HA) is angiogenic and is involved in tumor metas-
tasis, whereas high-MW HA (HMW-HA) is viscous, nonadherent to cells,
and acts as a lubricant. On the other hand, HMW-HA is believed to adhere
to cells in a polyvalent manner, leading to the formation of pericellular
sheaths that do not facilitate cell-cell and cell-growth factor interactions.
LMW-HA interacts with cellular receptors in a monovalent manner and
may lead to clustering of cell surface receptors (e.g., CD44) to activate
intracellular signaling cascades.
We have prepared photoreactive HMW-HA and LMW-HA, immobi-
lized them onto tissue culture substrates, and compared and contrasted
their effects on murine ES cells in vitro [33]. We hypothesized that they
would affect ES cell behavior differently. We demonstrated the presence
and interaction of the HA receptors CD44 and CD168 on these ES cells
and examined how these cell receptor-HA interactions determined cell
fates in vitro .