Tailoring bone microenvironment with 2D layered materials

The bone repair niche, including the physiological and pathological microenvironment, is a complex system that interferes with various cellular/noncellular activities. Thus, a rational perspective of designing tunable biomaterials with the modulation of the bone microenvironment is in high demand in pre/clinical practice for the management of refractory bone defects in combination with severe bone diseases. Two-dimensional (2D) layered materials are emerging biomaterials for bone microenvironment engineering because of their inherent biocompatibility, osteo-inductivity, osteo-conductivity, optical properties, enzyme mimetics, and mechanical properties. In this study, we focus on the latest advances in developing 2D layered materials in bone regeneration, bone cancer therapies, bone-related infections eradication, and articular cartilage repair. In addition, the specific action mechanisms and design regimens of 2D-layered material-based nanoplatforms are clarified. Finally, the current challenges are discussed, and the key inspirations for further broadening the pre/clinical applications of 2D layered materials in orthopedic disorder therapy are proposed.