Biomedical Engineering Reference
In-Depth Information
and also led to greater ectopic bone formation
in vivo
, compared to
HA hydrogels without dermatan sulfate or heparin [94].
HA scaffolds have also been modified by other chemical treatments to
improve their osteogenic and mechanical properties. Divinylsulfone-
crosslinked HA was incubated in a simulated body fluid to form
an apatite layer [95]. These constructs supported better alkaline
phosphatase activity and osteocalcin gene expression by MC3T3-E1
cells than cells grown on an atelocollagen sponge [95]. Further,
the HA constructs led to higher levels of bone formation
in vivo
in a rat calvarial defect model [95]. Similarly, HYAFF 11 sponges
treated with bioactive glass and supersaturated simulated body fluid
promoted biomimetic apatite crystal formation and proliferation
and mineralisation of MSC [96]. As a final example, to improve
the mechanical properties of HA, carbon nanotubes functionalised
with HA were used to create reinforced hydrogels. These hydrogels
did not exhibit signs of toxicity, and both HA hydrogels with and
without carbon nanotubes led to an increase in bone formation in a
rat molar extraction socket model [97, 98].
2.7.3 Hyaluronic Acid Carriers with Calcium Phosphate
Particles
HA has been used, both in soluble and crosslinked forms, as a carrier
for calcium phosphate particles to stimulate bone regeneration. In a
subcutaneous implantation model, an injectable paste-like material,
consisting of beta-tricalcium phosphate (β-TCP), methylcellulose,
and HA, increased the half-life of the β-TCP particles and ultimately
vascularisation of the implantation bed [99]. In a unilateral tibial
defect model in rabbits, the same formulation promoted a significant
increase in new bone volume fraction after one week; however, by
4 weeks, there was no difference in bone formation compared to
controls [100]. Similarly, medical grade HA of three different MW
(900,000 - Artz; 1,900,000 - Suvenyl; and 6,000,000 - Synvisc)
were evaluated as carriers for octacalcium phosphate granules in a
mouse subperiosteal calvarial model [101]. The formulations with
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