Tetrahedral Framework Nucleic Acid-Based Small RNA Delivery: Prospects and Challenges in Bone and Cartilage Regeneration.

Bone and cartilage defects represent major clinical challenges, with an increasingly urgent need for effective repair and regeneration. In recent years, small RNA-based regulatory strategies, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), have emerged as promising candidates for promoting bone and cartilage regeneration. However, achieving efficient and safe targeted delivery remains a critical challenge. Tetrahedral framework nucleic acids (tFNAs), a type of three-dimensional DNA nanomaterial with precise structure and excellent biocompatibility, serve dual functions as both intelligent delivery carriers and bioactive scaffolds, offering innovative solutions to this challenge. This review systematically outlines the advantages and research progress of tFNAs in this field, with a particular focus on their latest strategies and mechanisms as carriers for loading small RNAs that promote bone and cartilage regeneration. Additionally, the article summarizes cutting-edge investigations into enhancing the targeting ability, stability, and therapeutic efficacy of tFNAs through functional modifications and integration with biomaterials, and discusses the challenges and future directions for clinical translation.