Functionalized alginate-based bioinks for microscale electrohydrodynamic bioprinting of living tissue constructs with improved cellular spreading and alignment

Bioprinting has been widely investigated for tissue engineering and regenerative medicine applications. However, it is still difficult to reconstruct the complex native cell arrangement due to the limited printing resolution of conventional bioprinting techniques such as extrusion- and inkjet-based printing. Recently, an electrohydrodynamic (EHD) bioprinting strategy was reported for the precise deposition of well-organized cell-laden constructs with microscale filament size, whereas few studies have been devoted to developing bioinks that can be applied for EHD bioprinting and simultaneously support cell spreading. This study describes functionalized alginate-based bioinks for microscale EHD bioprinting using peptide grafting and fibrin incorporation, which leads to high cell viability (>90%) and cell spreading. The printed filaments can be further refined to as small as 30 μm by incorporating polyoxyethylene and remained stable over one week when exposed to an aqueous environment. By utilizing the presented alginate-based bioinks, layer-specific cell alignment along the printing struts could be observed inside the EHD-printed microscale filaments, which allows fabricating living constructs with cell-scale filament resolution for guided cellular orientation. Graphic abstract: [Figure not available: see fulltext.].