INJECTABLE HYDROGELS AS BIOMATERIALS - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 190

Several protein-based self-assembling hydrogels are currently being investi-
gated as unique, injectable biomaterials for wide range of applications. Most of
these proteins/peptides self assemble in the presence of appropriate stimuli to
form nanostructured matrices highly suitable for tissue engineering applications.
A self-assembling peptide composed of typically 8-16 amino acids has been
developed as an injectable system [Zhang, 2003]. The peptide will be in solution
at low pH and osmolarity but rapidly assemble to form fi bers of

5 - 10 nm in
diameter at physiological pH and osmolarity. The gels formed were found to be
highly cytocompatible towards many types of mammalian cells [Holmes et al.,
2000; Semino et al., 2003; Davis et al., 2005]. The potential of these injectable self-
assembling gels as drug delivery vehicles has also been demonstrated [Nagai
et al., 2006]. The studies demonstrate the versatility of chemical cross-linking sys-
tems as injectable biomaterials for biomedical applications.

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6.3.3 Thermogelling Polymers
Thermogelation is one of the most favored and extensively investigated strategies
for developing in situ gelling polymers. Pluoronics and various PEG-based poly-
mers form the most widely investigated thermogelling polymers. Pluoronics
present several advantages such as mild processing and gelling process, ability
to increase the stability of encapsulated proteins, and good biocompatibility.
The biomedical applications of Pluoronics based polymers as a drug or macro-
molecular delivery vehicle have been reviewed [Ruel-Gariepy and Leroux, 2004].
However, the low mechanical integrity of the gel, non-degradability, limited
stability with quick dissolutions and high permeability limits its biomedical
application [Liu et al., 2007].
Several degradable block co-polymers with hydrolytically sensitive blocks
such as poly(lactic acid/glycolic acid) or poly(caprolactone) as the hydrophobic
units and poly(ethylene glycol) as the hydrophilic units were therefore developed
[Cohn et al., 2006; Jeong et al., 2000; Chen et al., 2005]. The thermogelling
properties, combined with their biocompatibility and biodegradability, make
these polymers potential candidates for various applications. Furthermore, these
polymers have signifi cant potential as injectable drug delivery vehicles due to
the ability of these polymers to solubilize highly hydrophobic drugs.
Another unique approach to incorporate thermogelling properties to macro-
molecules is by grafting PEG to various polymers. Bhattarai et al. were able to
develop thermo-reversible hydrogels from chitosan functionalized with PEG.
PEG grafting signifi cantly increased the solubility of chitosan at neutral pH and
enabled gelation at physiological pH [Bhattarai et al., 2005a,b]. However, further
cross-linking using genipin has been suggested for developing protein delivery
vehicles due to the high permeability of the PEG-grafted gels. Mikos et al. have
developed a thermosensitve triblock copolymeric system by combining methoxy
poly(ethylene glycol) with poly(propylene fumarate). The system provides the
additional advantage of further chemical cross-linking using fumarate double
bonds. The thermogels are being evaluated as chondrocyte delivery vehicles