Synthesis and Characterization of Dual Stimuli-Sensitive Biodegradable Polyurethane Soft Hydrogels for 3D Cell-Laden Bioprinting.

Three-dimensional bioprinting serves as an attractive platform to fabricate customized tissue-engineered substitutes from biomaterials and cells for the repair or replacement of injured tissues and organs. A common challenge for 3D bioprinting materials is that the structures printed from the biodegradable polymer hydrogels tend to collapse because of the poor mechanical stability. In this study, dual stimuli-responsive biodegradable polyurethane (PU) dispersions (PUA2 and PUA3) were synthesized from an eco-friendly waterborne process. Acrylate group was introduced in the PU chain end to serve as a photosensitive moiety for UV-induced cross-linking and improvement of the printability, while mixed oligodiols in the soft segment remained to be the thermosensitive moiety. The photo/thermal-induced morphological changes of PU nanoparticles were verified by dynamic light scattering, small-angle X-ray scattering, and rheological measurement of the dispersions. It was observed that these PU nanoparticles became more rod-like in shape after UV treatment and formed compact packing structures upon further heating. With the thermosensitive properties, these UV-cured PU dispersions underwent rapid thermal gelation with gel moduli in the range 0.5-2 kPa near body temperature. The rheological properties of the PU hydrogels including dynamic viscoelasticity, creep recovery, and shear thinning behavior at 37 °C were favorable for processing by microextrusion-based 3D printing and could be easily mixed with cells before printing to produce cell-laden constructs. The dual-responsive hydrogel constructs demonstrated higher resolution and shape fidelity as well as better cell viability and proliferation than the thermoresponsive control. Moreover, the softer hydrogel (PUA3) with a low modulus (<1 kPa) could offer neural stem cells a tofu-like, stable, and inductive 3D microenvironment to proliferate and differentiate. We expect that the photo/thermoresponsive biodegradable polyurethane ink may offer unique rheological properties to contribute toward the custom-made bioprinting of soft tissues.