INJECTABLE HYDROGELS AS BIOMATERIALS - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 191

[Behravesh et al., 2002; Fisher et al., 2004]. PEG-grafted polyphosphazenes form
another class of injectable biodegradable hydrogels developed for biomedical
applications. The unique feature of these hydrogels is that the versatility of
polyphosphazenes would enable the development of systems with controllable
degradation and release profi les for drug/cell delivery applications [Sohn et al.,
2004; Park and Song., 2006; Kang et al., 2006a,b].
Another non-degradable polymer extensively investigated as a thermogel-
ling system is based on Poly(N-isopropylacryamide) (pNiPAAm) or its copoly-
mers [Schild, 1992]. The low biocompatibility and non-degradability of the
homo - polymer limits the in vivo applications of pNiPAAm; however, several
copolymeric systems are currently under evaluation as potential injectable ther-
mosensitve polymers. A promising system recently developed is a copolymer of
NiPAAm with water-soluble chitosan. The polymer has shown to undergo gela-
tion at 37 °C and the effi cacy of the system as a cell delivery vehicle has also been
demonstrated. The feasibility of using the system for the minimally invasive treat-
ment of vesicouretral refl ux with an endoscopic procedure through a single injec-
tion has been suggested [Cho et al., 2004]. Copolymer of NiPAAm with gelatin
has also been investigated as a thermogelling injectable biodegradable system for
cell encapsulation. Encapsulated smooth muscle cells showed high proliferation
and matrix synthesis in the case of gels with high pNiPAAm to gelatin ratio
presumably due to the hydrophobicity of NiPAAm units leading to larger aggre-
gates within the matrix and thereby providing high porosity and pore size struc-
ture to the matrix [Ohya et al., 2005].
Many natural polymers exhibit innate thermosensitve gelation process and
therefore have been investigated as in situ gelling systems. Methyl cellulose is
a biocompatible polysaccharide that exhibits thermo gelling properties. The
thermogelation of methyl cellulose has been attributed to the hydrophobic
interaction between polymeric molecules containing methoxy groups. As the
temperature of the aqueous solution of the polymer increases to 37 °C, hydrogen
bonds between the polymer and surrounding solvent break, and hydrophobic in-
teraction between the polymer chains led to gel formation. This simple sol-gel
transition in methyl cellulose has been used for developing injectable biomateri-
als. A fast gelling, injectable system was developed by blending methyl cellulose
with HA (to take advantage of the unique visocoelastic properties of HA) for
intrathecal delivery of bioactive molecules [Gupta et al., 2006; Shoichet et al.,
2007]. Bioactive methyl cellulose derivatives were also prepared by chemically
grafting protein to methyl cellulose backbone after periodate oxidation. The
oxidized and functionalized methyl cellulose promoted neuronal adhesion,
proliferation and viability and hence has potential for neuronal tissue engineer-
ing [Stabenfeldt et al., 2006].
Hydroxy butyl chitosan (HBC) is another class of temperature-sensitive
water soluble polysaccharide that is attracting signifi cant attention. Dang et al.
evaluated the feasibility of encapsulating mesenchymal stem cells and interverte-
bral disk cells in rapidly gelling HBC composition as an injectable matrix/cell
therapeutic for treating degenerative disk disease. The gels maintained a certain