Wood-based nanocellulose and bioactive glass modified gelatin–alginate bioinks for 3D bioprinting of bone cells

摘要

A challenge in the extrusion-based bioprinting is to find a bioink with optimal biological andphysicochemical properties. The aim of this study was to evaluate the influence of wood-basedcellulose nanofibrils(CNF) and bioactive glass(BaG) on the rheological properties of gelatin–alginatebioinks and the initial responses of bone cells embedded in these inks. CNF modulated the flowbehavior of the hydrogels, thus improving their printability. Chemical characterization by SEM-EDXand ion release analysis confirmed the reactivity of the BaG in the hydrogels. The cytocompatibility ofthe hydrogels was shown to be good, as evidenced by the viability of human osteoblast-like cells(Saos-2) in cast hydrogels. For bioprinting, 4-layer structures were printed from cell-containing gels andcrosslinked with CaCl2. Viability, proliferation and alkaline phosphatase activity (ALP)weremonitored over 14 d. In the BaG-free gels, Saos-2 cells remained viable, but in the presence of BaG theviability and proliferation decreased in correlation with the increased viscosity. Still, there was aconstant increase in the ALP activity in all the hydrogels. Further bioprinting experiments wereconducted using human bone marrow-derived mesenchymal stem cells(hBMSCs), a clinicallyrelevant cell type. Interestingly, hBMSCs tolerated the printing process better than Saos-2 cells and theALP indicated BaG-stimulated early osteogenic commitment. The addition of CNF and BaG togelatin–alginate bioinks holds great potential for bone tissue engineering applications.