Bioessential Inorganic Molecular Wire-Reinforced 3D-Printed Hydrogel Scaffold for Enhanced Bone Regeneration

Materials with physicochemical properties and biological activities similar to those of the natural extracellular matrix are in high demand in tissue engineering. In particular, Mo₃Se₃⁻ inorganic molecular wire (IMW) is a promising material composed of bioessential minerals and possess nanometer-scale diameters, negatively charged surfaces, physical flexibility, and nanotopography characteristics, which are essential for interactions with cell membrane proteins. Here, an implantable 3D Mo₃Se₃⁻ IMW enhanced gelatin-GMA/silk-GMA hydrogel (IMW-GS hydrogel) is developed for osteogenesis and bone formation, followed by biological evaluations. The mechanical properties of the 3D printed IMW-GS hydrogel are improved by noncovalent interactions between the Mo₃Se₃⁻ IMWs and the positively charged residues of the gelatin molecules. Long-term biocompatibility with primary human osteoblast cells (HOBs) is confirmed using the IMW-GS hydrogel. The proliferation, osteogenic gene expression, collagen accumulation, and mineralization of HOBs improve remarkably with the IMW-GS hydrogel. In in vivo evaluations, the IMW-GS hydrogel implantation exhibits a significantly improved new bone regeneration of 87.8 ± 5.9% (p < 0.05) for 8 weeks, which is higher than that from the gelatin-GMA/silk-GMA hydrogel without Mo₃Se₃⁻ IMW. These results support a new improved strategy with in vitro and in vivo performance of 3D IMW enhanced scaffolds in tissue engineering.