Chitosan Derivatives - Chitosan Based Hydrogels: Functions and Applications - page 83

NH 3 +

HOH 2 C

HO O 1st tier

OH

O

O

O

NH 3 +

HOH 2 C

COO -

OH

COO -

HO OH

O

O O

O O

O

HO

O HO

HN O HO

HN

HS

O

S O

OH + 2nd tier

OH

O

N

O

O

O

N-(CH 2 O)nN O

N

O

O

O

+

S

O N 3rd tier

GCGYGRGDSPG

H 2 N

H

O

Figure 2.38
Three-tiered membrane/coating structure and their respective chemistries. First tier: chitosan membrane/coat-
ing; second tier: polyanion-PEG conjugate (e.g., alginate-PEG conjugate), which forms a polyelectrolyte complex
with the first tier. Third tier: ligand (e.g., RGD) conjugated to the second tier by maleimidyl chemistry. (From
Wan, A. C. A. et al. 2008. Langmuir 24: 2611-2617. With permission.)

tier) and the ligand (third tier). Human marrow stromal cells (hMSCs) seeded onto RGD-
modified chitosan membranes exhibit good adhesion and spreading of cells and could be
further endowed with signals to affect stem cell proliferation and/or differentiation. The
RGDS sequence is immobilized on chitosan scaffolds by the formation of imide bonds
between amino groups on chitosan and carboxyl groups on peptides. The concentration of
the immobilized RGDS in chitosan is measured to be on the order of 10 −12 mol/cm 2 [307].
The GRGDS sequence is a very intriguing member of the RGD family. R V β 3 , R V β 5 , and
RIIbβ 3 are integrins most reported to be involved in bone function [308]. They can be
immobilized on the chitosan film surface with 10 −9 mol/cm 2 . Using photochemical immo-
bilization technology, RGDS sequences can be immobilized onto chitosan films with
10 −7 mol/cm 2 of relatively higher concentrations (as shown in Figure 2.39) . Nishimura and
coworkers [309] established a facile and efficient method for the conjugation of chitosan
with sulfhydryl-containing synthetic peptide on the basis of 2-iminothiolane-mediated
selective cross-linking in a mild and homogeneous solution ( cf. Figure 2.40). Chitosan-
RGDSGGC conjugates exhibited excellent cell adhesion and proliferation activity for chon-
drocytes and fibroblasts.

2.11.8 graft Copolymerization based on living radical Polymerization

Great progress has been made in the last decade on the development of controlled/living
radical polymerization methods [310,311]. The most widely used controlled/living radical
polymerization (CLRP) methods are nitroxide-mediated polymerization, atom transfer rad-
ical polymerization (ATRP), and degenerative-based methods such as reversible addition
fragmentation transfer (RAFT) and iodine transfer. These methods are applicable to a wide
range of monomers, solvents, and end functionalities. CLRP methods allow the synthesis of