Bioprinting of bioglass-alginate/carboxymethyl cellulose for bone tissue engineering

Bone regenerative medicine requires suitable substitutes that promote osteogenesis. Most of the bio-macromolecular hydrogels are promising because they are biocompatible and biodegradable, but their viscoelastic properties make them challenging to use, especially in 3D bioprinting applications. This study aimed to enhance the mechanical properties of a bone substitute made of bioprinted alginate, carboxymethyl cellulose, and 58S bioglass. We used dual cross-linking and optimized the concentration of cross-linking agents to improve hydrogel biological activity and mechanical stability. The compression test indicated that the combination of Ca²⁺ and Fe³⁺ significantly improved the mechanical properties of the alginate/carboxymethyl cellulose hydrogel. The hydrogel crosslinked with 4% Ca²⁺ and 1.5% Fe³⁺ showed the highest Young's modulus. The study also found that the hydrogel rigidity influenced cell proliferation capability during bioprinting, as observed in the cell viability results. At day 7, the cell viability of the bioprinted constructs cross-linked with 0.5% and 1% Fe³⁺ exhibited significant increases. Similarly, these groups also demonstrated the highest alkaline phosphatase (ALP) activity at the same time. Results suggested that cross-linking density and resultant rigidity achieved by optimal concentrations of Fe³⁺ have very significant effects on cell viability and osteogenesis.