Double-Network Polyurethane-Gelatin Hydrogel with Tunable Modulus for High-Resolution 3D Bioprinting

Three-dimensional (3D) bioprinting is a technology to print materials (bioink) with cells into customized tissues for regeneration or organoids for drug screening applications. Herein, a series of biodegradable polyurethane (PU)-gelatin hydrogel with tunable mechanical properties and degradation rates were developed as the bioink. The PU-gelatin hydrogel demonstrated good printability in 24–31 °C and could print a complicated structure such as the nose-shaped construct. Due to the excellent shear thinning and fast strain recovery properties, the PU-gelatin hydrogel also had long working windows for bioprinting (over 24 h), stacking ability (up to 80 layers), and feasibility for high-resolution printing (through an 80 μm nozzle). The structure stability of the PU-gelatin hydrogel was maintained by two-stage double-network formation through Ca2+ chelation and thermal gelation at 37 °C without any toxic cross-linking reagent. The compressive modulus of printed PU-gelatin hydrogel constructs increased in about 3-fold by the treatment of CaCl2 solution for 15 min and enhanced further after incubation because of the thermal sensitivity of PU at 37 °C. Mesenchymal stem cells (MSCs) printed with the PU-gelatin hydrogel through the 80 μm nozzle showed good viability, high mobility, and ∼200% proliferation ratio (or an ∼300% proliferation ratio through a 200 μm nozzle) in 10 days. Furthermore, the MSC-laden PU-gelatin constructs containing small molecular drug Y27632 underwent chondrogenesis in 10 days. The novel series of PU-gelatin hydrogels with tunable modulus, long working window, convenient bioprinting process, and high-resolution printing possibilities may serve as new bioink for 3D bioprinting of various tissues.