Formation of Chitosan-Based Hydrogels Network - Chitosan Based Hydrogels: Functions and Applications - page 200

Chitosan

NH + NH +

COO -

N-H N-H

COO -

C=O C=O

Covalent bond

NHSO - OSO -

Heparin Alginate

Figure 4.13
Heparin-functionalized chitosan-alginate PEC. (From Ho, Y. C. et al. 2009. Int J Pharm 376: 69-75. With
permission.)

Chondrocytes seeded in the chitosan-alginate-heparin-bFGF actually show significant
higher viability. bFGF is a primary promoter of cell proliferation, which stimulates the
proliferation and migration of chondrocytes. Moreover, heparin can recognize and bind
bFGF via the bioaffinity interaction, and coupling of heparin onto the scaffold is beneficial
for the stable conjugation of bFGF under mild conditions. This may in turn help in preserv-
ing the bioactivity of the cell growth factor [152].

4.3.2 interpenetrating Network

Entangled polymer networks can be further strengthened by interlacing secondary poly-
mers within the cross-linked networks. Here, a cross-linked chitosan network is allowed
to swell in an aqueous solution of polymer monomers. These monomers are then polym-
erized, forming a physically entangled polymer mesh called an interpenetrating polymer
network (IPN). There are also semi-IPNs, where only one of the polymer networks is
cross-linked, while the second polymer remains in its linear state. If the second polymer
is also cross-linked, a full-IPN is formed. There are several chitosan-based semi-IPNs and
full-IPNs. This technique allows for the specific selection of polymers that can comple-
ment the deficiencies of one another. Although the cross-linking density, hydrogel poros-
ity, and gel stiffness can be adjusted in IPN-based hydrogels according to the target
application, they have difficulty encapsulating a wide variety of therapeutic agents, espe-
cially sensitive biomolecules. In addition, IPN preparation requires the use of toxic agents
to initiate or catalyze the polymerization or to catalyze the cross-linking. Complete
removal of these materials from the hydrogel is challenging, making the clinical applica-
tion problematic [6].

4.3.2.1 Semi-IPNs

The states of water in hydrogels and their relative amounts exert a considerable effect on
the permeability and selectivity of hydrogel membranes. The activity of biological
systems, such as proteins and enzymes, depends on how the water molecules associate
with these biopolymers. Cross-linked chitosan-polyether semi-interpenetrating polymer
network (cr-CS-PE semi-IPN) was synthesized and the state and mobility of water in
cr-CS-PE semi-IPN were investigated using differential scanning calorimetry (DSC) and
nuclear magnetic resonance (NMR), respectively. The results indicate that the states and