Tetrahedral Framework Nucleic Acid Composite Hydrogel Loaded with Naringin for Full Alveolar Bone Regeneration

The complexity of the endogenous tissue structure and exogenous healing environment complicates the study of alveolar bone regeneration in regenerative medicine. Naringin (Nar), a flavonoid monomer found in traditional Chinese medicines, induces osteogenesis in bone marrow mesenchymal stem cells (BMSCs) <i>in vivo</i> and therefore is well suited for bone injury treatment. However, the clinical applications of Nar are limited by its low bioavailability and room-temperature solubility in water. To address these drawbacks, Nar was herein loaded on tetrahedral framework nucleic acids (tFNAs), which are formed by the complementary pairing of four single-stranded DNA molecules and show excellent prospects for delivering small-molecule drugs and nucleic acid sequences. The resulting tFNA-Nar nanocomposite (TNC) exhibited a high stability and cellular uptake efficiency, and the effects of this composite on the biological behavior and osteogenic properties of BMSCs were elucidated using <i>in vitro</i> assays. Furthermore, a rat model of full-thickness alveolar bone defects was developed and treated with a chitosan hydrogel and TNC as composite scaffolds for alveolar bone regeneration. The results of morphological, immunohistochemical, and immunofluorescence analyses performed at 2 and 4 weeks posttreatment indicated that TNC effectively promoted the remodeling of the cortical and cancellous alveolar bones and shed light on the underlying molecular mechanism. Thus, TNC was concluded to combine the advantages of tFNAs and Nar and facilitate full-thickness alveolar bone repair, holding promise as a nucleic acid-based nanomaterial for bone tissue regenerative medicine.