Hyaluronic Acid Incorporation into Scaffolds for Bone and Cartilage Regeneration - Hyaluronic Acid for Biomedical and Pharmaceutical Applications - page 37

Cartilage Regeneration

2.7.2 Hyaluronic Acid Combinations with Other Materials

HA has been combined with a number of naturally derived and
synthetic polymers to improve its osteoconductive/osteoinductive and
mechanical properties for use in bone repair applications. A mixture
of HA, CS, and dermatan sulfate led to healing of a critical size rat
calvarial defect [88]. Interestingly, unfilled defects in the treated
animals also healed, suggesting a potential systemic effect [88]. In
another study, membranes of collagen and HA were formed by self-
assembly (in one step, in contrast to the layer-by-layer techniques
described below) at the interface of the two solutions; BMP-2 was
incorporated by addition to the collagen solution. These membranes
sustained the release of BMP-2 and led to greater alkaline phosphatase
activity by MSC in vitro and to ectopic mineral deposition in vivo
[89]. A different formulation of collagen combined with sulfated HA
led to increased calcium phosphate deposition and tissue non-specific
alkaline phosphatase expression, more so than with native (non-
sulfated) HA [90]. As another example, a thermoresponsive hydrogel,
consisting of HA- g -chitosan- g -poly( N -isopropylacrylamide), was
used to encapsulate bone marrow-derived MSC. The constructs
promoted cell proliferation, alkaline phosphatase activity, and
mineralisation in vitro as well as led to ectopic bone formation in vivo
[91]. Additionally, amphiphilic graft copolymers of HA (at various
weight percentages) and high density polyethylene, achieving storage
moduli in the range of 2.4 to 15.0 MPa, supported bone marrow
stromal cell attachment and mineralisation in vitro [92].

Additionally, HA has been combined with other materials to improve
its ability to complex osteogenic growth factors. Heparin is a sulfated
GAG that can bind BMP-2 and has been incorporated into HA
scaffolds to sustain the release of this molecule [93, 94]. Interestingly,
while HA scaffolds functionalised with heparin slowed the release of
BMP-2 and maintained its osteogenic activity in vitro , HA scaffolds
with BMP-2 but without heparin (thus having a higher burst release)
led to more bone formation in an ectopic site in vivo [93]. In another
study, BMP-2 complexed with dermatan sulfate or heparin prior to
loading in an HA hydrogel extended the release of the BMP-2 in vitro