Soft, Deformable Polyurethane-Boronic Acid Nanoparticles as Dynamic Cross-Linkers to Construct 3D-Bioprintable Hydrogels.

Addition of nanoparticles in a hydrogel can enhance its three-dimensional (3D) printability. However, the role of soft, deformable nanoparticles in the 3D printability of a hydrogel network has not been explored so far. In this study, two boronic acid-functionalized polyurethane (PU) nanoparticles PUB and PUB' are synthesized as soft dynamic nanocross-linkers to construct a 3D bioprintable hydrogel. The soft segment of PUB consists of poly(ε-caprolactone) (PCL) solely while that of PUB' consists of PCL, poly(d,l-lactide), and poly(3-hydroxybutyrate) in a 0.7/0.2/0.1 molar ratio. Small-angle X-ray scattering (SAXS) reveals that PUB nanoparticles are nearly spherical while PUB' nanoparticles are ellipsoidal. A PUB'-cross-linked poly(ethylene glycol) hydrogel based on dynamic click chemistry has greater shear modulus and creep resistance than a PUB-cross-linked hydrogel. When printed through a small (160 μm) nozzle, the PUB'-based hydrogel exhibits superior stackability and filament resolution. Time-resolved SAXS analysis unveils that PUB' nanoparticles elongate and maintain a stable ellipsoidal morphology in the network during gelation, contributing to a higher packing density (particle volume fraction 38%) and 3D stackability of the hydrogel. Meanwhile, PUB nanoparticles transform from spherical to ellipsoidal and are eventually flattened, leading to a low packing density (particle volume fraction 18%) of the hydrogel. Moreover, endothelial cells laden in both hydrogels show high vitality (∼92%). The unique shape deformation phenomenon of the PU-boronic acid nanocross-linker during gelation and the resulted high-density packing in the dynamic network provide insights into the role of soft nanoparticle morphology in the stackability of a dynamic self-healing hydrogel and the role of particle packing in designing 3D hydrogel inks.