Formation of a Novel Heparin-Based Hydrogel in the Presence of Heparin-Binding Biomolecules

Abstract

An injectable, heparin-based hydrogel system with the potential to be gelled with cells was developed. First, heparin was modified to have thiol groups by the modification of carboxylic groups of heparin with cysteamine using carbodiimide chemistry. Thiol functionalization of heparin carboxylic groups was controlled from 10% to 60% of the available COOH groups, and the retained bioactivity of the modified heparin, characterized by its binding affinity to antithrombin III, decreased with increasing functionalization. Then, the thiol-functionalized heparin was reacted with poly(ethylene glycol) diacrylate to form a hydrogel. The gelation kinetics and mechanical properties of the final gel state could be tuned by controlling cross-link density. Fibroblast cell encapsulation using this hydrogel revealed the nontoxicity of the present system. Cell proliferation inside the hydrogel was observed, and it was significantly enhanced (more than 5-fold) by the addition of fibrinogen into the hydrogel during gelation.