INJECTABLE HYDROGELS AS BIOMATERIALS - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 188

A new class of thiol-based system has been proposed to circumvent some
of these limitations. The thiolated polymers can form degradable networks
through Michael-addition-type reaction through acrylate, acrylamide or vinyl
sulfone groups as well as by direct polymerization of thiol acrylates [Lutolf and
Hubbell, 2003; Vernon et al., 2003]. The thiol-based systems enable the formation
of a cross-linked network with better control over the cross-link density, elimi-
nate high molecular weight degradation products as the degradable segments get
incorporated throughout the network, could even eliminate the need for a photo-
initiator, allow samples to be cured to depths exceeding ten cm, and therefore
have signifi cant potential as an in situ gelling system for cell encapsulation
[Rydholm et al., 2005].
Another unique strategy to overcome the concerns of cell or tissue damage
due to direct UV exposure is by forming an in situ gellable photo polymerizable
system with a long induction period. Di-acrylated Pluoronic F127 has shown
to have a long induction period after UV irradiation before macrosocpic gelation
can occur. The polymer solution can therefore be injected after UV irradiation
and will attain the gel state following injection [Lee and Tae, 2007]. Further
studies on these unique injectable systems will demonstrate their potential for
various biomedical applications.

6.3.2 Hydrogels Formed by Fast Chemical
Reaction/Physical Transitions
The versatility of thiolated polymers allows for the development of in situ gelling
polymers without using initiators. Michael type reaction has therefore been inves-
tigated to form in situ gels. A hyaluronic acid based hydrogel was formed in situ
using thiolated hyaluronic acid [Shu et al., 2006]. However, the rate of gelation of
thiolated polymers is very slow, making them less than optimal candidates as in-
jectable systems. The addition of acrylated polymers to thiolated polymers sig-
nifi cantly increased the rate of gelation, thereby making them suitable for use as
injectable systems. Recently, Michael-addition has also been used to develop in-
jectable in situ forming chitosan-based hydrogels. Chitosan was functionalized
with acrylate groups and then reacted with thiolated poly(ethylene oxide) to
form the in situ forming gels [Kim et al., 2007].
Polymerization of acrylated polymers can also be performed without photo
irradiation in the presence of redox reagents, such as ammonium persulfate, as
free radical generators. Biodegradable injectable hydrogel material based on
the oligomer “oligo(poly(ethylene glycol) fumarate)” polymerized using redox
reagents is another class of PEG-based biomaterial developed for treating carti-
lage lesions [Holland et al., 2005]. The effi cacy of the injectable hydrogel system
as an excellent protein delivery vehicle has also been demonstrated [Park et al.,
2005]. Rabbit marrow mesenchymal stem cells encapsulated in the fumarate gels
showed the ability to differentiate into chondrocytes in the presence of slowly
released transforming growth factor-

1). The studies demonstrate the
potential of the system for cartilage tissue engineering [Park et al., 2007].

β 1 (TGF - β