Hyaluronic Acid-based Scaffolds for Brain Tissue Engineering - Hyaluronic Acid for Biomedical and Pharmaceutical Applications - page 127

by adding various crosslinkers and catalysts, such as carbodiimide,
hydroxybenzotriazole, and N -hydroxysuccinimide.
Since the hydrophilic polyanionic surface of HA does not
thermodynamically favour cell attachment and subsequent tissue
formation, two major strategies have been used to improve the cell
attachment onto HA-based scaffolds. One is to physically coat or
mix ECM proteins onto the HA scaffold and the other method is to
chemically link ECM proteins or their functional domains to the HA
backbone by covalent bonding. The cell adhesion and migration can
be enhanced by modifying HA hydrogels with ECM components or
their peptide motifs, namely laminin, arginine-glycine-aspartic acid
(RGD), isoleucine-lysine-valine-alanine-valine (IKVAV), poly(D-
lysine) or poly(L-lysine) (PLL). Hou and co-workers were the first to
report significant results in this area. For instance, they observed that
the modification of HA with laminin improved tissue reconstruction,
reducing the number of astrocytes gathering around the boundary
of the host tissues and the HA hydrogel scaffold and promoting
new fibre formation within the scaffolds [35]. Besides laminin, some
biomimetic peptide motifs such as RGD and IKVAV were immobilised
onto HA hydrogels to promote cell adhesion. RGD modification was
demonstrated to significantly enhance cell migration into implants
[36], which is similar to the situation in IKVAV modification [37].
Blending HA with collagen is also a good option to promote cell
adhesion and thus enhance neural regeneration. Wang and Spector
reported that blending HA with collagen enabled the fabrication of
scaffolds with suitable mechanical properties for CNS regeneration
[38].
6.4.2 Delivery of Bioactive Cues using Hyaluronic Acid-
based Scaffolds
Modification of HA-based scaffolds with bioactive peptides or
proteins is a feasible method for promoting CNS regeneration. As
the main ECM component with a high molecular weight of over
2 million, HA has several advantages as a biomaterial for controlled