Biomedical Engineering Reference
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scaffolds loaded with TGF-1 were reported to promote cartilage regenera-
tion [43, 44]. CS scaffolds loaded with epidermal growth factor resulted
in the promotion of chondrogenesis [45]. The CS/( N,N -dicarboxymethyl)
scaffolds, loaded with BMPs, have been reported to induce the healing of
articular cartilage lesion in rabbit [46].
1.4.2 HA-basedMaterials
Hyaluronan (HA), a ubiquitous component of the extracellular matrix
(ECM) of all connective tissues, is a non-sulfated glycosaminoglycan
(GAG), consisting of repeating disaccharide units ( b -1,4-D-glucuronic acid
and b -1,3- N -acetyl-D-glucosamine) [47]. The ECM is a network composed
of covalent and non-covalent interactions between GAGs and proteins.
For example, chondroitin sulfate is covalently linked to proteoglycans
which, in turn, have HA-binding modules that form multivalent high-
affi nity interactions with HA. These protein-ligand interactions stabilize
and organize the ECM [48, 49], regulate cell adhesion and motility [50, 51],
and mediate cell proliferation and differentiation [52]. As a consequence,
HA and its derivatives have been widely investigated as materials for cell
growth and tissue repair in biomedical applications [53-62].
HA has also been modifi ed by the addition of functional group using
crosslinking method to form a hydrogel [63]. This maintained chondro-
cyte viability and phenotype, and promoted the chondrogenic differen-
tiation of MSCs when cultured in both in vitro and in vivo [63]. However,
ECM distribution is limited without adequate space for diffusion due to
slow degradability of this hydrogel. Ideally, scaffold degradation should
match with ECM deposition and accumulation. Degradation can alter the
diffusion of nutrients and waste, cell-scaffold interactions, and the distri-
bution and retention of ECM proteins. Therefore, to control degradation
of a scaffold, it is crucially important to select an appropriate approach:
either chemical crosslinking and/or copolymerization of functional group
on the backbone of HA. The MSCs encapsulated in HA functionalized
hydrogels retained a rounded cell morphology [64], and the tuning of
temporal scaffold properties can control neocartilage production by MSCs
in this gel. The most important criterion of hydrogel must be the mechani-
cal stability and control of degradation which can be done via crosslink-
ing of methacrylate and aldehyde groups, ultimately leading to cartilage
repair [65]. A careful balance of slow and fast degradable components and
mechanical stability are the most important criteria for optimal growth of
functional cartilage tissue.
HA is known to interact with chondrocytes via various surface recep-
tors involved in sophisticated signaling pathways, which allow chondro-
cytes to maintain their original phenotype [66]. In addition, HA has been
conjugated to alginate, CS and fi brin gel matrices to provide artifi cial ECM
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