Development and Application of Naturally Renewable Scaffold Materials for Bone Tissue Engineering - The Nanoscience and Technology of Renewable Biomaterials - page 299

Hyaluronan is another polysaccharide that has made a large impact on bone tissue
engineering. Hyaluronan, also known as hyaluronic acid, is an anionic, nonsulfated,
high molecular weight glycosaminoglycan and was first isolated from the vitreous body
of the eye (22). It is a natural mucopolysaccharide that consists of alternating residues
of D-glucuronic acid and N-acetyl-D-glucosamine. Commercially, hyaluronan can be
derived from bacterium such as streptococcus zooepidium and extraneous bovine mate-
rials. Hyaluronan's main function is to provide tissue hydration based on its hygroscopic
nature (22). It functions as the backbone of the proteoglycan aggregates necessary for
the integrity of articulating cartilage such as found in joints. Hyaluronan is preferentially
expressed by cells during wound healing to aid in cell migration and proliferation. Due
to the correlation of hyaluronan expression during wound healing, researchers have long
been supplementing bone defects with exogenous hyaluronan in combination with bone
graft materials. Hyaluronan and its derivatives have been used as topical, injectable, and
wholly implantable biomaterials for the delivery of bioactive compounds (86). In fact,
it is the orginal lastoviscous biomaterial for applications in eye surgery, bone surgery,
otology, plastic surgery, and rheumatology (87). From a biomechanical perspective,
by itself or with fibropectin, it may be a potentially optimal bioimplant for vocal fold
defects and scarring (88). Interestingly, like chitosan, it too demonstrates antibacterial
activity, especially when applied for guided tissue regeneration surgery (89). Addition-
ally, it has shown enhanced activity for the treatment of noninfected, mechanical corneal
lesions where the time for epithelial defect closure was significantly reduced compared
to nontreated corneas (90).
The versatility of hyaluronic acid for biomedical applications is seemingly limitless,
especially with respect to its use for prodrugs, delivery vehicle, and tissue scaffold. In
the area of prodrugs, hyaluronic acid can be modified chemically to develop polymeric
structures for simple drug applications such as analgesics (91). When grafted with
poly(ethylene glycol) (PEG), it was possible to incorporate insulin preferentially into the
PEG phase of this copolymer to provide 'leakage' (92). Indeed, the release was solely
dependent upon the PEG content.
In terms of delivery vehicle, it has been used as an osteogenic or chondrogenic delivery
vehicle upon a similar modification (to PEG) with glucuronic acid (93). These types of
carrier have been shown by this work to be superior in terms of their delivery volume and
osteo- or chondrogenic ability relative to traditional porous calcium phosphate ceramics.
Finally, and most relevant to this chapter, hyaluronan's tolerability and biocompati-
bility as a three-dimensional tissue scaffolding matrix is very acceptable. For example,
studies done with rabbit autologous mesenchymal progenitor cells showed that the cells
adhered and proliferated on hyaluronan (94). In Vivo , when the cell-seeded hyaluro-
nan was implanted, there was no inflammatory response and the scaffold completely
degraded after four months of implantation.
Surgical applications have also benefited from composite structures that include
hyaluronan, specifically hyaluronan in combination with alginates (95). Alginates are
linear polysaccharides, derived from seaweed, and are composed of D-mannuronic and
L-guluronic acid residues. When in the presence of divalent cations, notably calcium,
a semisolid gel can be formed through the ionic crosslinking between the carboxylic
acid groups located along the polymer chain. This entrapment is known as the eggbox
model where two chains are ionically bound to the calcium ion (96). This system