Cellulose Nanocrystal-Enhanced Thermal-Sensitive Hydrogels of Block Copolymers for 3D Bioprinting

The hydrogel formed by polyethylene glycol-aliphatic polyester block copolymers is an ideal bioink and biomaterial ink for three-dimensional (3D) bioprinting because of its unique temperature sensitivity, mild gelation process, good biocompatibility, and biodegradability. However, the gel forming mechanism based only on hydrophilic-hydrophobic interaction renders the stability and mechanical strength of the formed hydrogels insufficient, and cannot meet the requirements of extrusion 3D printing. In this study, cellulose nanocrystals (CNC), which is a kind of rigid, hydrophilic, and biocompatible nanomaterial, were introduced to enhance the hydrogels so as to meet the requirements of extrusion 3D printing. First, a series of poly(ε-caprolactone/lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone/lactide) (PCLA-PEG-PCLA) triblock copolymers with different molecular weights were prepared. The thermodynamic and rheological properties of CNC-enhanced hydrogels were investigated. The results showed that the addition of CNC significantly improved the thermal stability and mechanical properties of the hydrogels, and within a certain range, the enhancement effect was directly proportional to the concentration of CNC. More importantly, the PCLA-PEG-PCLA hydrogels enhanced by CNC could be extruded and printed through temperature regulation. The printed objects had high resolution and fidelity with effectively maintained structure. Moreover, the hydrogels have good biocompatibility with a high cell viability. Therefore, this is a simple and effective strategy. The addition of the hydrophilic rigid nanoparticles such as CNC improves the mechanical properties of the soft hydrogels which made it able to meet the requirements of 3D bioprinting.