Tuning the Properties of Hydrogel Microspheres by Adding Chemical Cross-linking Functionality to Sodium Alginate

Two novel types of hydrogel microspheres (MS) are presented. First, one-component microspheres (1-comMS) were produced from sodium alginate (Na-alg) equipped with thiol-functionalized hydroxyl groups. The functionalization pathway included the conversion of Na-alg into tetrabutylammonium alginate, insertion of new carboxyl groups, grafting of α-amine-ω-thiol poly(ethylene glycol), and restoration of the sodium salt. This modification conserves all original carboxyl groups of Na-alg and allows for covalent disulfide bond formation in addition to ionic cross-linking. Second, two-component microspheres (2-comMS) were obtained from a mixture of Na-alg and Na-alg functionalized with cysteamine. This functionalization was achieved by grafting cystamine dihydrochloride on some carboxyl groups followed by the reduction to cysteamine. Using the one-step MS formation process developed for both MS types, very fast ionic gelation with calcium ions conserves the spherical shape of the polymer solution droplets upon extrusion into the gelation bath, while simultaneously occurring slow covalent cross-linking reinforces the hydrogels. The physical properties of both MS types are adjustable by varying the polymer concentration, the degree of grafting, and the mixing ratio. In vitro cell microencapsulation studies confirmed the cytocompatibility of 1-comMS and 2-comMS.