Biomimetic Polysaccharides and Derivatives for Cartilage Tissue Regeneration - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 12

environments [67]. However, the hydrophilic, polyanionic surfaces of HA
biomaterials do not thermodynamically favor cell attachment and tissue
formation [68]. Therefore, to enhance cell interactions, surfaces coated
with ECM proteins such as type I collagen and fi bronectin, have been
developed by creating physically or covalently linked functional domains
[69, 70]. Physical and biological characteristics of HA in its purifi ed form,
such as water solubility, rapid resorption, short residence time in the tis-
sue, etc., limit its application as biomaterial [71]. Several attempts have
been made to modify HA molecular structure and improve its properties.
Covalent photo-induced crosslinking has been used to overcome these
limitations and to provide long-term stability and increased mechani-
cal strength [72]. For instance, porcine chondrocytes, encapsulated in
photopolymerized HA hydrogels maintained viability and were able
to produce neocartilage within the porous networks during 8 weeks
in in vitro experiments [73]. The ethyl and the benzyl esters of hyaluro-
nan named HYAFF®7 and HYAFF®11, respectively, are two of the most
characterized hyaluronan derivative polymers. Both physicochemi-
cally and biologically they degrade at predictable rates through hydro-
lysis of the ester bonds (around 2 months for complete hydrolysis) [71].
Human chondrocytes, grown onto HYAFF®11 3D scaffolds, are able to
re-express in vitro their differentiated phenotype [74], and to reduce the
expression and production of molecules involved in cartilage degenera-
tive diseases [75]. Histological evaluation of repaired tissue by HYAFF®11
scaffold, employed in chondrocyte transplantation in vivo , demonstrated
a signifi cant improvement of the quality of the healing in comparison to
defects without grafted chondrocytes (Figure 1.3) [76].
1.4.3 Alginate-basedMaterials
Alginate is a naturally occurring linear polysaccharide, composed of
(1-4)-linked b -D-mannuronic acid (M units) and a -L-guluronic acid (G units),
with varying proportion and sequential distribution along the polymer
chain. This polymer is known to be biocompatible [77] and forms hydro-
gels in the presence of multivalent cations (i.e., Ca 2+ ) by ionic interaction
between the carboxylic acid groups, located on the backbone of this poly-
mer and the chelating cation [78]. Researchers have developed calcium
crosslinked alginate hydrogels for a variety of biomedical applications,
including cell culture and transplantation, drug delivery and wound
dressing [79-82]. Generally alginate is used in its physical form of hydro-
gels, which do not signifi cantly enhance cell migration and proliferation,
mainly due to their small pore sizes (nm scale). In order to achieve macro-
porous structure of scaffold, the lyophilization of alginate hydrogels was
employed [83]. In a separate study, Eiselt et al. [83] developed a method for
fabrication of macroporous alginate beads with high porosity (78%) and