Bioactive nanoparticle reinforced alginate/gelatin bioink for the maintenance of stem cell stemness

Highlights: • A novel bioactive nanoparticle reinforced bioink enhances stemness of MSCs. • Addition bioactive nanoparticles in bioink shows good printability. • Silicon ions play an important role in stemness maintenance. Mesenchymal cells (MSCs) are an attractive option as seed cells for bioprinting. However, loss of stemness and undesired differentiation reduces their effectiveness. In this study, 12 nm bioactive nanoparticles (BNPs) which could release silicon (Si) ions were used to enhance the properties of alginate/gelatin hydrogel bioink to maintain MSC stemness. By specifically leveraging biochemical signals of BNPs, bioink with defined stiffness towards osteogenic and adipogenic potential, independent of pore structure, were designed by incorporating with different concentration of BNPs. These bioink were characterized by printability, mechanical and rheological properties as well as osteogenic and adipogenic potentials. Notably, the effect of 2% BNPs addition in alginate/gelatin hydrogel on MSC stemness maintenance was confirmed by the expression of stemness markers. At higher concentrations of BNPs (5%), printability was impacted by the gelling process. We further confirmed the enhanced stemness maintenance by sweat gland lineage commitment of bioprinted MSCs in vitro. Overall, our study proved that alginate/gelatin hydrogel bioink reinforced by BNPs in the optimal concentrations could retain MSC stemness as well as support MSC growth and prolong the desired differentiation. These findings may provide a new approach to achieve the ideal therapeutic potential of MSCs in 3D bioprinting application.