Laponite Nanocomposite Hydrogels for Bone Tissue Engineering: A Critical Review of Bioactivity and Translational Perspectives

Bone tissue engineering has emerged as a promising alternative to conventional grafting approaches for treating critical-sized bone defects. To overcome the limitations of conventional biomaterials, considerable effort has been directed toward the development of bioactive nanocomposite hydrogels. Among the nanomaterials used in these systems, Laponite (LAP), a synthetic nanoclay composed of disk-shaped nanosilicate platelets, stands out due to its unique physicochemical properties, including high surface area, shear-thinning behavior, ionic dissolution products, and strong interactions with polymers, proteins, and cells. Across diverse polymer systems, incorporation of LAP consistently improves rheological and mechanical performance, facilitating injectable formulations while enhancing structural stability and shape fidelity for extrusion-based bioprinting. However, the magnitude and biological consequences of these effects depend on polymer chemistry, LAP concentration and dispersion, crosslinking, and construct architecture. LAP nanocomposite hydrogels also exhibit pronounced osteoinductive capacity, promoting osteogenic differentiation of mesenchymal stem cells through sustained release of bioactive ions, including silicon, magnesium, and lithium, and activation of bone-related signaling pathways. In addition, LAP-containing hydrogels influence key components of the regenerative microenvironment by supporting angiogenesis and modulating immune responses. Preclinical studies across multiple animal defect models generally demonstrate enhanced bone formation, mineralization, vascularization, and defect healing compared with LAP-free controls. Despite these encouraging findings, important translational challenges remain. Long-term biocompatibility, degradation behavior, biodistribution of degradation products, manufacturing reproducibility, scalability, and regulatory requirements have not yet been comprehensively addressed. Furthermore, most evidence is derived from short- to medium-term preclinical studies, with limited data from large-animal models and no established clinical applications to date. Collectively, this review provides a balanced assessment of LAP nanocomposite hydrogels, highlighting both their considerable potential and the key scientific, safety, and regulatory barriers that must be overcome to enable successful clinical translation.