Norbornene-functionalized methylcellulose as a thermo- and photo-responsive bioink

Three-dimensional (3D) bioprinting has emerged as an important tool to fabricate scaffolds with complex structures for tissue engineering and regenerative medicine applications. For extrusion-based 3D bioprinting, the success of printing complex structures relies largely on the properties of bioink. Methylcellulose (MC) has been exploited as a potential bioink for 3D bioprinting due to its temperature-dependent rheological properties. However, MC is highly soluble and has low structural stability at room temperature, making it suboptimal for 3D bioprinting applications. In this study, we report a one-step synthesis protocol for modifying MC with norbornene (MCNB), which serves as a new bioink for 3D bioprinting. MCNB preserves the temperature-dependent reversible sol-gel transition and readily reacts with thiol-bearing linkers through light-mediated step-growth thiol-norbornene photopolymerization. Furthermore, we rendered the otherwise inert MC network bioactive through facile conjugation of integrin-binding ligands (e.g. CRGDS) or via incorporating cell-adhesive and protease-sensitive gelatin-based macromer (e.g. GelNB). The adaptability of the new MCNB-based bioink offers an attractive option for diverse 3D bioprinting applications.