Abstract
https://onlinelibrary.wiley.com/doi/full/10.1002/adfm.202400431
Aqueous two-phase emulsion (ATPE)-based bioinks, a creative innovation for bioprinting, enable the fabrication of complex 3D cell-laden hydrogels with macroporous structure, which promote cellular activities within the scaffold. However, these bioinks intrinsically lack stability and specific biofunctionality, potentially limiting their application for targeted tissue engineering. This study proposes a new perspective by introducing less than 0.1% phosphorylated cellulose nanofibrils (pCNF), a 1D nanofibril top-down produced from natural biomasses, into a dextran/methacrylated gelatin (GelMA)-based ATPE system for extrusion-based bioprinting of preosteoblastic cells, aiming to fabricate macroporous hydrogels with osteogenic differentiation potential. The pCNF that is selectively partitioned in the GelMA phase can not only improve the emulsion stability and alter the rheological behaviors of the ATPE-based bioink, but also enhance the damping capacity and mineralization ability of the crosslinked hydrogels. Furthermore, macroporous hydrogels with pCNF demonstrate increased cell activity and higher viability in post-printing, along with higher alkaline phosphatase activity and osteoblastic gene expression. Importantly, the organized interfaces within the hydrogel facilitate the formation of macroscopic biomineralized nodules in vitro. The incorporation of multifunctional pCNF in the ATPE system significantly boosts the physiochemical and biological performance of the macropore-forming bioink, transforming them into a suitable platform for engineering in vitro bone models.
