Nanocellulose-Reinforced 4D Printed Hydrogels: Thermoresponsive Shape Morphing and Drug Release

Four-dimensional (4D) printed polymer composite hydrogels with stimuli-responsive shape-morphing features are attractive to fabricate dynamic multifunctional structures for the upcoming next generation of biomedical applications. Poly(N-isopropylacrylamide) (PNIPAM) is an attractive polymer choice, as it undergoes a phase transition at a temperature similar to our body, but it suffers from poor printability and low mechanical properties. In the present work, we demonstrated a thermoresponsive hydrogel printing ink, PNIPAM/Alginate (Alg) reinforced with elastic biosourced nanocellulose fibers, to enable anisotropic shape morphing at and above 36 °C. During direct ink writing, a shear-induced alignment of cellulose fibrils within the ink followed by ionic and light-driven cross-linking of the gel led to an improved shape fidelity of the bilayer printed architectures. Printed TEMPO-oxidized CNF (TCNF)-reinforced hydrogels revealed appreciable overall and higher directional mechanical properties as compared to the CNF-reinforced construct. The TCNF-based sample showed tensile strength, Young’s modulus, and toughness values of 150 kPa, 6.77 MPa, and 83 kJ m^–3 and 50 kPa, 7.3 MPa, and 16 kJ m^–3 in the longitudinal and transverse directions, respectively. Furthermore, a higher value of controlled drug release from the TCNF-containing printed sample than that from the casted sample revealed promising benefits of the former for antimicrobial activity. The cross-linked temperature-dependent degree of swelling, on immersion in water, of the printed dynamic hydrogel with temperature-programmable control is showcased by the optimized ink formulation. Different mechanical and physical properties in different printing directions, due to intrinsic anisotropy and fiber direction alignment, provided a facile method for 4D printing of thermoresponsive shape-morphing functional architectures. The present strategy reveals potential for exploration of the devised sustainable ink formulation in a variety of biomedical applications such as tissue engineering and soft robotic devices.