Bone tissue engineering has risen to tackle the challenges of the current clinical need concerning bone fractures that is already considered a healthcare system problem. Scaffold systems for the repair of this tissue have yielded different combinations including biomaterials with nanotechnology or biological agents. Herein, three-dimensional porous hydrogels were engineered based on gelatin as a natural biomaterial and reinforced with synthetic saponite nanoclays. Scaffolds were biocompatible and shown to enhance the inherent properties of pristine ones, in particular, proved to withstand pressures similar to load-bearing tissues. Studies with murine mesenchymal stem cells found that scaffolds had the potential to proliferate and promote cell differentiation. In vivo experiments were conducted to gain insight about the ability of these cell-free scaffolds to regenerate bone, as well as to determine the role that these nanoparticles in the scaffold could play as a drug delivery system. SDF-1 loaded scaffolds showed the highest percentage of bone formation, which was corroborated by osteogenic markers and new blood vessels. Albeit a first attempt in the field of synthetic nanosilicates, these results suggest that the designed constructs may serve as delivery platforms for biomimetic agents to mend bony defects, circumventing high doses of therapeutics and cell-loading systems.