Extrusion-based 3D bioprinting enables the fabrication of complex, cell-laden constructs for applications in biomedical engineering and cultivated meat. Alginate–gelatin hydrogels reinforced with cellulose have emerged as promising bioinks due to their rheological tunability and initial cytocompatibility. However, conventional formulations often lack long-term stability and fail to support adequate cell–matrix interactions, limiting their applicability in tissue maturation processes. To address these challenges, we evaluated alginate di-aldehyde (ADA)–gelatin hydrogels reinforced with bacterial cellulose as bioinks for C2C12 myoblasts. ADA introduces covalent Schiff base interactions with gelatin, enhancing cellular adhesion and reducing gelatin leaching, but its susceptibility to hydrolysis compromises scaffold’s stability. Here, we demonstrate that bacterial cellulose improved hydrogel stability, and that continuous supplementation of Ca²⁺ in the culture medium sustained long-term ionic crosslinking, resulting in stable constructs with high cell viability over time. This combined strategy, leveraging ADA chemistry, cellulose reinforcement, and dynamic Ca²⁺ supplementation, offers a new route to designing bioinks that balance cytocompatibility with structural robustness, advancing the development of functional scaffolds for both regenerative medicine and cultivated meat production.
Guadalupe et al. (Tue,) studied this question.