INJECTABLE HYDROGELS AS BIOMATERIALS - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 187

expression allowing longer lasting therapeutic effect without repeated treatment
[Quick and Anseth, 2003]. Photopolymerization has shown to increase the stabil-
ity of encapsulated plasmid DNA when administrated in vivo . Moreover, since
photointiatiated polymerization allows spatial and temporal control of gelation,
the process could permit creation of patterned matrices in vivo with different
concentrations of the transfecting agents as well as plasmids that encode several
different tissue inducing proteins.
Even though photo gelation is a mild process, the encapsulated DNA was
found to denature within the photo polymerized gel. It has been found that the
denaturation of plasmid DNA is not due to the light used (

365 nm) but due to
the free radicals that induce photo polymerization. Later studies by Anseth et al.,
revealed that addition of radical scavengers such as vitamin C and complexing
plasmid DNA with transfection agents (such as protamine sulfate) could preserve
the integrity of the plasmid DNA during photo polymerization. The feasibility of
photo cross-linkable injectable gel to encapsulate and release plasmid DNA in an
active, supercoiled form in a sustained manner has been demonstrated. Photo
cross-linked PEG hydrogels released DNA for periods of six to one hundred
days, with nearly linear or delayed burst release profi les and the released DNA
exhibited high biological activity as evidenced from cell culture studies [Quick
and Anseth, 2004 ].
Apart from synthetic polymers, several degradable natural polymers
modifi ed with acrylic groups have been investigated as injectable photo cross-
linkable systems for biomedical applications [Leach et al., 2003]. Since natural
polymers are present in many tissues, they provide a better biomimetic environ-
ment for tissue engineering application compared to synthetic polymers. The ef-
fi cacy of hyaluronic acid based photo cross-linked gels as a potential matrix for
creating a tissue engineered heart valve has been demonstrated by encapsulating
valvular interstitial cells with high viability in photo cross-linked gels. High ma-
trix and signifi cant elastin production by the encapsulated cells were observed
after six weeks in culture [Masters et al., 2005]. The effi cacy of hyaluornic acid
injectable gels for cartilage tissue engineering has also been demonstrated
[Nettles et al., 2004]. A recent study demonstrated the effi cacy of functionalized
chondroitin sulfate as an effi cient photo cross-linkable tissue adhesive system
[Wang et al., 2007]. Chondroitin sulfate was functionalized with methacrylate
groups for photo cross-linking and aldehyde groups for chemically bridging the
hydrogel to the tissue proteins. In vitro and in vivo studies (in goat models) dem-
onstrated the mechanical stability of the construct during tissue repair in cartilage
defects [Wang et al., 2007].
Even though degradable injectable photo cross-linkable systems present
unique advantages for a wide range of biomedical applications, some of the limi-
tations of the system include residual high molecular weight compounds upon gel
degradation, mild toxicity associated with the photoinitiators, limited control
over the network evolution mechanism during chain-growth, and also light
attenuation by the initiators restricting the maximum attainable cure depth of
only a few millimeters [Rydholm et al., 2005; Baroli, 2006].

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