In vitro evaluation of antibacterial activity and biocompatibility of synergistically cross-linked gelatin-alginate hydrogel beads as gentamicin carriers

Abstract

This work aimed to develop biodegradable millimeter-scale spherical hydrogel beads with highly interconnected pores, which effectively serve dual functions for cell growth and antibiotic release. Sodium alginate and gelatin were used as the matrix for the hydrogel beads, which were synergistically cross-linked by using different ratios of the cross-linkers N-ethyl-N-(3-dimethylaminopropyl) carbodiimide and calcium chloride. Spherical porous hydrogel beads after sucrose leaching were prepared with particle sizes of 2–3 and 4–6 mm. Their physicochemical properties, including pore size, surface and cross-sectional morphology, degree of crosslinking and free amines, swelling, and degradation, were measured. Selected 2–3 mm hydrogel beads were further impregnated with gentamicin and analyzed for biocompatibility and antibacterial activity. The results showed that the synergistically cross-linked hydrogel was an internally porous structure with a porosity of about 80% and a uniform pore size distribution between 90 and 212 μm, with no significant difference in the average pore size of 160 μm for all beads. After soaking for 24 h, the beads absorbed approximately 50 times their weight (w/w) while maintaining a stable pore size without significant swelling. The cross-linker concentration of carbodiimide/CaCl2 was chosen to be 1/0.5 wt% to reduce the cytotoxicity that might be caused by the release of Cl ions. The polar interaction of the hydrogel with gentamicin accelerate the degradation of the beads after impregnation with the antibiotic gentamicin, resulting in a burst release of the antibiotic. Therefore, the gentamicin-impregnated hydrogel beads had better antibacterial activity compared with the hydrogel without antibiotics. However, these gentamicin-impregnated beads had reduced resistance to hydrogel degradation and biocompatibility. The developed hydrogel beads had good antibacterial activity and can be used in combination with different medical devices to further improve biocompatibility and reduce the risk of surgical failure caused by infection.