INJECTABLE HYDROGELS AS BIOMATERIALS - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 189

Polymeric aldehydes derived from polysaccharides can be used for develop-
ing injectable fast gelling systems due to their chemical reactivity. Polymeric alde-
hydes are mainly developed using periodate chemistry from polysaccharides
having vic - diols. An in situ gelling system formed by self cross-linking oxidized
alginate and gelatin in the presence of small concentrations of borax without
using any extraneous cross-linking agent has been reported [Balakrishnan and
Jayakrishnan, 2005]. The fast gelling composition was found to be non-toxic as
evidenced from in vitro cell culture studies. The ability of the gels to function as a
heptocyte encapsulation matrix and as a wound dressing has been demonstrated
[Balakrishnan et al., 2005]. The evaporative water loss through the gel has been
found to be closer to the range appropriate to maintain proper fl uid balance on
the wound bed, indicating its potential as an injectable wound dressing. More-
over, the presence of borax has been shown to have some antibacterial properties
promoting accelerated wound healing.
One of the potent applications of injectable systems is to act as barriers
to prevent tissue adhesion following surgery or other injuries. An in situ gelling
injectable hyaluronic acid-based system with marked in vivo anti - adhesion
property was developed. The injectable system is based on hyaluornic acid-
aldehyde and hyaluronic adipic dihydrazide. A fast gelation reaction occurs by
mixing these two solutions due to the formation of a hydrazone compound. The
system has also shown effi cacy to be used as an effective drug delivery vehicle to
enhance biological activity in vitro and in vivo [Yeo et al., 2007a,b]. Apart from
HA, several other polysaccharides have also been investigated to develop inject-
able gels using similar chemistries [Ito et al., 2007].
Another versatile in situ gelling system developed is known as “click gels”
based on “click chemistry.” Room temperature gelation happens when hyaluronic
acid (HA) bearing azido groups is reacted with an alkyne derivative of HA in the
presence of catalytic amounts of cuprous chloride. The gelation is due to dipolar
cycloaddition or Huisgen reaction, a type of click chemistry process. The study
demonstrated the feasibility of varying the cross-linking density of the gel, as well
as the effi cacy of the gel as a drug and cell delivery vehicle [Crescenzi et al., 2007].
Another emerging technique for developing an in situ gelling system is based
on enzyme-catalyzed cross-linking reaction. Several cross-linking systems using
polymers containing glutaminamide and amines in the presence of transgluta-
minase (TG) and calcium ions as co-factors have been developed [Sperinde and
Griffi th, 1997; Sanborn et al., 2002; McHale et al., 2005]. A glutaminamide-
functionalized poly(ethylene glycol) and poly(lysine-co-phenylalanine) was used
by Sperinde and Griffi th to form injectable gels in the presence of TG. TG medi-
ated covalent cross-linking occurs via the formation of an amide linkage between
the carboxy amide groups of peptidyl glutamine residues and primary amine of
lysine residues. Several synthetic and natural polymers functionalized with tyra-
mine, tyrosine or aminophenol side groups are currently under development that
can form in situ gels by phenol or aniline derivative coupling using hydrogen per-
oxide as an oxidant catalyzed by horseradish perodidase (HRP) [Sofi a et al., 2002;
Kurisawa et al., 2005; Kobayashi et al., 2001; Jin et al., 2007].