INJECTABLE HYDROGELS AS BIOMATERIALS - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 179

for biomedical applications. Stimuli sensitive hydrogels have been broadly classi-
fi ed into two systems: stimuli-responsive systems and stimuli-sensitive gelling
systems.
Stimuli-responsive systems show marked swelling and de-swelling changes
or degradation in response to various stimuli. The property has been used for
controlling the release of entrapped molecules as well as pulsatile release of drugs
or macromolecules from hydrogel depot systems. Bio-responsive hydrogels
change properties (swelling/de-swelling, degradation) in response to selective
biological recognition events such as nutrient, growth factor, receptor, antibody,
enzyme or whole cell [Ulijin et al., 2007]. The release of insulin from bio-respon-
sive hydrogels in response to raised blood sugar is one of the interesting systems
developed [Fischel-Ghodsian et al., 1988]. Bio-responsive hydrogels are also used
for bio-sensing applications. Kim et al., developed a whole cell sensing system
based on the interaction of immobilized lymphocytes with target peptides [Kim
et al., 2006]. Similarly, Hubbell et al., have developed a PEG-based ECM mim-
icking hydrogel scaffold that permits cell migration via the enzymatic cleavage of
oligopeptides used as cross-linkers. These oligopeptides are cleavable by matrix
metalloproteinases (MMPs), which belong to a family of enzymes that play a
signifi cant role during tissue remodeling. The presence of oligopeptides in the
gel allows the invading cells to degrade the hydrogels by secreting MMPs,
facilitating complete tissue regeneration [Lutolf and Hubbell, 2005]. Stimuli-re-
sponsive hydrogels, therefore, fi nd applications in diagnostics, drug delivery and
tissue regeneration.
In the case of stimuli-sensitive gelling systems, the aqueous polymer solution
change into a gel in response to a particular stimulus, thus enabling the formation
of gel in situ . The practical biomedical applications of these materials arise from
their injectability that allows for non-invasive treatment strategies. An injectable
in situ -gelling system can be injected into a complex defect site and gelled to form
a solid structure of exactly the same dimension. The in situ formed gels generally
show increased adhesion to surrounding tissue due to the intimate contact of the
gel with the tissue during formation and by the mechanical interlocking resulting
from surface micro-roughness [Elisseeff et al., 1999]. Biocompatible injectable
stimuli-sensitive gelling polymers are potential biomaterials for drug delivery and
tissue engineering applications.
This chapter reviews various types of injectable in situ gelling hydrogels cur-
rently being investigated as biomaterials, mainly for tissue regeneration with an
emphasis on photo, chemical and thermo-gelling polymers.
6.3 INJECTABLE IN SITU FORMING GELS
Recent years saw an exponential increase in research towards developing in situ
gelling materials due to their considerable applicability interest in such areas
as protein and cell carriers, implants as well as other medical devices. Their
advantages as protein delivery vehicle include ease of formulation, high-loading