Hyaluronic Acid Incorporation into Scaffolds for Bone and Cartilage Regeneration - Hyaluronic Acid for Biomedical and Pharmaceutical Applications - page 24

2.4 Typical Chemical Modifications of Hyaluronic Acid
to Form Scaffolds for Bone and Cartilage
Although HA is degraded rapidly by hyaluronidase in vivo [36], its
facile tunability helps to overcome this limitation [4]. HA can be
chemically modified to increase its half-life, thus helping to control
the degradation and mechanical stability of the scaffold [4, 37, 38].
Properties of the scaffolds can be tailored by altering the molecular
weight (MW) of the HA macromer, the percentage of modification
and so on. Modifications via esterification, etherification, thiol/
disulfide chemistry, and amidation, among others, primarily focus
on reactions with (a) the carboxylic acid group (-COOH) of the
glucuronic acid subunit or (b) the hydroxyl group (-OH) of the
acetylglucosamine subunit ( Figure 2.1 ) [37].
2.4.1 Esterification and Etherification
Esterification and etherification are the two most commonly used
methods to modify HA to form a scaffold while maintaining its
biocompatibility [39, 40]. The -COOH group of the glucuronic acid
subunit can be reacted with an alcohol, for example benzyl alcohol,
to form an ester, in this case benzyl ester ( Figure 2.1a ) [40]. This
modification also increases the hydrophobicity of the HA macromer,
thus prolonging its degradation time. These hydrophobic modified HA
compounds can be made into scaffolds via electrospinning, for example,
into fibres, meshes, and membranes. In particular, this chemistry is used
to prepare the commercially available HYAFF 11 scaffold [39-42].
In contrast, etherification modifies the -OH group on the
acetylglucosamine subunit. Two primary methods of etherification
involve reacting HA under basic conditions with either glycidyl
methacrylate, forming one type of methacrylated HA ( Figure 2.1f ),
or methacrylic anhydride, forming another methacrylated HA
( Figure 2.1g ) [43, 44]. Scaffolds are then formed through crosslinking
via photoinitiated polymerisation [37]. The generated free radicals
initiate a chain-growth polymerisation of the reactive groups on