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

[[abstract]]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 degrees 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 mum nozzle). The structure stability of the PU-gelatin hydrogel was maintained by two-stage double-network formation through Ca(2+) chelation and thermal gelation at 37 degrees 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 degrees C. Mesenchymal stem cells (MSCs) printed with the PU-gelatin hydrogel through the 80 mum nozzle showed good viability, high mobility, and approximately 200% proliferation ratio (or an approximately 300% proliferation ratio through a 200 mum 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