Potential Applications of Multifunctional Tetrahedral Framework Nucleic Acids in Bone Tissue Engineering

Though bone defects are common, treating critical-sized bone defects remains a significant clinical challenge. A potential strategy for bone repair that avoids the need for autogenous bone grafts is bone tissue engineering (BTE). Recently, BTE strategies incorporating vascularization, neurorestoration, and immunomodulation of bone substitutes are regarded as a comprehensive and promising method for bone repair. Despite advancements, existing approaches struggle to achieve overall bone regeneration. Emerging DNA nanotechnology, specifically tetrahedral framework nucleic acids (tFNAs), presents a transformative approach due to their rapid self-assembly, structural stability, efficient cellular uptake, multiple biological activities, and excellent biocompatibility. tFNAs allow for flexible modifications with various bioactive molecules, including oligonucleotides, peptides, and small molecular drugs, thus strengthening their targeting and therapeutic abilities. tFNAs can enhance osteogenesis by promoting mesenchymal stem cell viability and differentiation, thereby stimulating bone formation. Furthermore, tFNAs integrated with scaffolds contribute to the development of advanced biomaterials with superior osteoinductive properties. tFNAs also influence angiogenesis, neurorestoration, and immunomodulation, all of which are crucial for bone repair. This review not only examines the potential applications of multifunctional tFNAs in BTE but also provides critical insights into the advantages, challenges, and prospects of tFNAs in BTE.