3D bioprinting allows the fabrication of 3-dimensional (3D) structures containing living cells whose 3D shape and architecture are matched to a patient. The feature is desirable to achieve personalized treatment of trauma or diseases. However, realization of this promising technique in the clinic is greatly hindered by inferior mechanical properties of most biocompatible bioink materials. Here, we report a novel strategy to achieve printing large constructs with high printing quality and fidelity using an extrusion-based printer. We incorporate cationic 2 nanoparticles in an anionic polymer mixture, which significantly improves mechanical properties, printability and printing fidelity of the polymeric bioink due to electrostatic interactions between the nanoparticles and polymers. Addition of cationic-modified silica nanoparticles to an anionic polymer mixture composed of alginate and gellan gum results in significantly increased zero-shear viscosity (1062 %) as well as storage modulus (486 %). As a result, it is possible to print a large (centimeter-scale) porous structure with high printing quality, whereas the use of the polymeric ink without the nanoparticles leads to collapse of the printed structure during printing. We demonstrate such a mechanical enhancement is achieved by adding nanoparticles within a certain size range (<100 nm), and depends on concentration and surface chemistry of the nanoparticles as well as the length of polymers. Furthermore, shrinkage and swelling of the printed constructs during crosslinking are significantly suppressed by addition of nanoparticles compared to the ink without nanoparticles, which leads to high printing fidelity after crosslinking. The incorporated nanoparticles do not compromise biocompatibility of the polymeric ink, where high cell viability (> 90%) and extracellular matrix secretion are observed for cells printed with nanocomposite inks. The design principle demonstrated can be applied for various anionic polymer-based systems, which could lead to achievement of 3D bioprinting-based personalized treatment.

The field of bioprinting has made significant recent progress towards engineering tissues with increasing complexity and functionality. It remains challenging, however, to develop bioinks with optimal biocompatibility and good printing fidelity. Here, we demonstrate enhanced printability of a polymer-based bioink based on dynamic covalent linkages between nanoparticles (NPs) and polymers, which retains good biocompatibility. Amine-presenting silica NPs (ca. 45 nm) were added to a polymeric ink containing oxidized alginate (OxA). The formation of reversible imine bonds between amines on the NPs and aldehydes of OxA lead to significantly improved rheological properties and high printing fidelity. In particular, the yield stress increased with increasing amounts of NPs (14.5 Pa without NPs, 79 Pa with 2 wt% NPs). In addition, the presence of dynamic covalent linkages in the gel provided improved mechanical stability over 7 days compared to ionically crosslinked gels. The nanocomposite ink retained high printability and mechanical strength, resulting in generation of centimetre-scale porous constructs and an ear structure with overhangs and high structural fidelity. Furthermore, the nanocomposite ink supported both in vitro and in vivo maturation of bioprinted gels containing chondrocytes. This approach based on simple oxidation can be applied to any polysaccharide, thus the widely applicability of the method is expected to advance the field towards the goal of precision bioprinting.

The field of bioprinting has made significant recent progress towards engineering tissues with increasing complexity and functionality. It remains challenging, however, to develop bioinks with optimal biocompatibility and good printing fidelity. Here, we demonstrate enhanced printability of a polymer-based bioink based on dynamic covalent linkages between nanoparticles (NPs) and polymers, which retains good biocompatibility. Amine-presenting silica NPs (ca. 45 nm) were added to a polymeric ink containing oxidized alginate (OxA). The formation of reversible imine bonds between amines on the NPs and aldehydes of OxA lead to significantly improved rheological properties and high printing fidelity. In particular, the yield stress increased with increasing amounts of NPs (14.5 Pa without NPs, 79 Pa with 2 wt% NPs). In addition, the presence of dynamic covalent linkages in the gel provided improved mechanical stability over 7 days compared to ionically crosslinked gels. The nanocomposite ink retained high printability and mechanical strength, resulting in generation of centimetre-scale porous constructs and an ear structure with overhangs and high structural fidelity. Furthermore, the nanocomposite ink supported both in vitro and in vivo maturation of bioprinted gels containing chondrocytes. This approach based on simple oxidation can be applied to any polysaccharide, thus the widely applicability of the method is expected to advance the field towards the goal of precision bioprinting.

Crosslinked SU-8 is a promising material for microfluidic and bio-MEMs applications because of its excellent optical properties, chemical stability, biocompatibility and low absorption of analytes. Thus, devices made out of SU-8 are very well suited for specialized applications such as live cell imaging. However, the design of monolithic SU-8 devices is often limited because the bonding of SU-8 layers usually requires a special bonding apparatus. Here, we present a reliable and user-friendly bonding method for SU-8 layers, which eases the fabrication of 3D SU-8 microfluidic devices. The top layer and the main layer of an SU-8 channel were bonded at pressures of 1, 2, 3, 4 and 8 kPa. The resulting bonding was free of voids in all cases, and the maximum bond strength was 6.5  ±  1.9 MPa, which is sufficient for most microfluidic applications. All the devices exhibited excellent stability under flow conditions. The device bonded at the lowest applied pressure (1 kPa) was tested for 24 h under a flow shear stress of 280 dynes cm−2 and showed no sign of leakage. Thus, the presented low-pressure bonding is a promising technique to fabricate SU-8 microfluidic devices.