HYALURONAN-BASED HYDROGEL SCAFFOLDS - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 170

Figure 9.3. Carbodiimide-mediated chemical reaction of HA. 17 − 21
Figure 9.4. Functionalization of HA with primary amines. 24 , 25
carbodiimide reaction is very sensitive to pH, frequently leading to
the formation of unreactive intermediate acylurea from carboxylic
acid,dependingonthereactionconditions,verylowcouplingyields
could beobtained(Fig. 9.3). 17 − 21
To avoid this problem, amino dihydrazaide has been employed
by the Prestwich group and others, forming functional amine end
groups. 22 Further grafting of bioactive molecules was performed
under mild basic conditions to its new primary amine end groups
viathe succinate-NHS ester reaction (Fig. 9.4). 23
9.3.3 Sulfydrylation (HA-SH)
Functionalizationof HA withthiolshasbeen developed for coupling
bioactivecompounds(Fig.9.5)andasubsequentself-couplingreac-
tionwithunsaturatedgroupsviaMichael-typeadditionreactionsby
the research groups of Hubbell 26 − 29 and Noh. 7 , 30 − 32 After coupling
the amino dihydrazide to the carboxylic acid of HA, an HA deriva-
tivewithdisulfidegroupsisformed.Thereductionofdisulfideleads
to sulfydryl end groups, which are important for further chemical
reactions such as acrylates end groups.
AsanotherexampleofanHAderivativewiththiolendgroups,the
HA has been coupled under basic conditions with ethylene sulfide
with some precipitation, probably due to ethylene sulfide oligomer-
ization (Figs. 9.6 and 9.7). 34 , 35 HA with sulfydrylate was obtained