Biomedical Engineering Reference
In-Depth Information
prefabrication reactionswithdifferentbiocompatiblepolymers, etc.
The following sessions describe detailed methods of chemical mod-
ification and hydrogelation of HA by using HA, HA derivatives, and
cross-linkers.
9.4.1 Hydrogel Formation by Direct Cross-Linking Methods
9.4.1.1 Diepoxy cross-linking method
Diepoxy cross-linkers have been employed for fabrication of HA
hydrogels via hydroxyl groups by using PEO diglycidyl ether, ethyl-
eneglycoldiglycidylether,1,4-butanedioldiglycidylether,andpolyg-
lycerolpolyglycidyletherunderbasicconditions. 21 , 37 Whilediepoxy
compounds demonstrated formation of ester linkages between
carboxyl groups at acidic condition, they formed ether linkages
betweenhydroxylgroupsatbasiccondition.Furthertwo-stepexper-
iments were performed on the basis of these results: an HA hydro-
gel was formed with diepoxyoctane via ester intra- and inter-
molecular linkages between HA at acid condition at a first step, and
then via ether linkages at basic condition. 38 This method demon-
stratedayieldofhydrogelformationthroughacross-linkingmethod
(Fig. 9.10).
9.4.1.2 Bifunctional amine cross-linkers
AsmentionedearlierintheHAderivertizationsession,carbodiimide
reactions are processed via the reactions between carboxylic acid
and amines. Simple fabrication of HA hydrogels via this carbodi-
imide reaction is achieved by using solely carbodiimide to induce
intra- and intermolecular cross-linking of HA with amine-derived
HA (Fig. 9.11). 38
To overcome no induction of similar reactions with HA in solu-
tion due to the formation of unreactive acylureas, Kuo et al . 39
Figure 9.10. Hydrogelformationviachemicalreactionofdiepoxideswith
HA-OH. 16 , 21
 
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