INJECTABLE HYDROGELS AS BIOMATERIALS - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 192

extent of mechanical integrity and the encapsulated cells proliferated and produced
a matrix within the gel during a period of up to two weeks [Dang et al., 2006].
Another chitosan-based thermogelling system that is attracting signifi cant
attention is chitosan-glycerophosphate mixture [Chenite et al., 2000; 2001]. The
uniqueness of the system lies in the transformation of pH-gelling cationic chito-
san solution into a thermally sensitive, pH-dependent gel forming solution capa-
ble of gelling at physiological temperature without any chemical modifi cation or
cross-linking. To produce thermo-gelling solution, polyols bearing single anionic
groups such as glycerol-, sorbitol, fructose or glucose-phosphate salts are slowly
added to a chitosan solution at a low temperature. The mechanism of gelation has
been attributed to a combination of favorable hydrogen bonding, electrostatic
interactions and hydrophobic interactions between polymer chains and with the
polyols. The thermogelling chitosan-glycerophosphate solution can be easily
administered endoscopically within the body or through injections to form in situ
gelling systems. The injectable system has been found to form homogeneous gel
implants after injection in many body compartments—subcutaneously, intrarticu-
larly, intra-muscularly, as well as in bone and cartilage defects. The good cytocom-
patibility of the gel was established using in vitro cell culture studies. The
mild gelling process of chitosan-glycerophosphate makes it a potential delivery
vehicle for bioactive proteins. A study investigated the effi cacy of chitosan-
glycerophosphate to deliver BMP-2 ectopically in a subcutaneous pouch in rats.
Figure 6.4 shows the feasibility of chitosan-glycerophosphate to subcutaneously
deliver active BMP-2, leading to de novo cartilage and bone formation in an
ectopic site [Chenite et al., 2000].
Chitosan-glycerophosphate solution, when mixed with whole blood, has
shown to coagulate in situ within 15 minutes when applied to cartilage defects
in vivo [Hoemann et al., 2007]. Furthermore, the chitosan-glycerophosphate-
blood mixture was found to have tissue adhesivity with minimal gel shrinkage,
showing its potential as an injectable scaffold for cartilage tissue engineering. The
chitosan-glycerophosphate-blood mixture has also been investigated to treat
marrow-stimulated chondral defects in rabbit and sheep cartilage repair models.
The application of chitosan-glycerophosphate-blood has been found to signifi -
cantly increase more cellular and hyaline repair leading to cartilage repair well
integrated with a porous subchondral bone structure compared to marrow stimu-
lation alone [Hoemann et al., 2005]. The increased healing of chondral defects
using chitosan-glycerophosphate-blood has been attributed to greater levels of
provisional tissue vascularization and bone remodeling activity due to the pres-
ence of in situ gels [Chevrier et al., 2007].
This author's laboratory has developed a similar injectable thermo-gelling
system based on chitosan using inorganic phosphate salts as the neutralizing and
thermo-gelling agent [Nair and Laurencin, 2007]. The in situ gelling system was
developed by adding ammonium hydrogen phosphate (AHP) to a chitosan solu-
tion at a low temperature. The system has been found to be highly versatile, with
gelling time varying from fi ve minutes to several hours at 37 °C, by varying the
concentration of the phosphate salt. Compared to the chitosan-glycerophosphate