HYALURONAN-BASED HYDROGEL SCAFFOLDS - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 174

Figure 9.11. Hydrogel formation via Chemical reactions of bifunctional
amines to HA-COOH. 19 − 21
developed a new bis -carbodiimide cross-linking technique. Sev-
eral bis -carbodiimides were synthesized and covalently bound to
HA through a mechanism similar to the acylurea formation, thus
producing aromatic or aliphatic inter-molecular cross-linking of
HA. Finally, several efforts to make reactions between HA's car-
boxyl groups and the amines of bifunctional cross-linkers have
been attempted. Several research groups made use of reactions
via carbodiimide and 1-hydroxybenzotriazole to couple activated
amines(e.g.,adipicdihydrazide[ADH])toHA'scarboxylgroups.Car-
bodiimide and N -hydroxysulfosuccinimide were used for coupling
reactions between HA' carboxylic acid and primary amines (e.g.,
1,4-diaminobutane dihydrochloride) under mild basic conditions. 18
Similarly, Vercryusse et al .andOh et al . have employed a variety
of polyvalent hydrazide cross-linkers (two to six hydrazides per
cross-linker and the succinate-NHS ester reaction) for synthesis of
HAhydrogelsviacarbodiimide-mediatedreactions 40 andgraftingof
bioactive molecules as well as for testing of its molecular degrada-
tion (Figs. 9.12 and9.13). 23
Recently, HA hydrogels fabricated through ADH cross-linking
have been prepared with some defined mesh sizes for tests of its
adhesion and proliferation of the lung carcinoma cell line H460M 41
and the adhesion barrier with antiadhesion drugs such as the glu-
cocorticoidreceptoragonistbudesonidewithintheabdominopelvic
cavity following surgery or other injuries. 42 While the defect
sites either with or without hydrogel addition induced a large
amount of adhesion, the site with hydrogel containing budesonide
Figure 9.12. Hydrogel formation via chemical reactions of dihydrazide
with HA. 17 − 21 , 24 , 25