GelMA Hydrogels Integrated With aptamer CH6‐Functionalized Tetrahedral DNA Nanostructures for Osteoporotic Mandibular Regeneration

Osteoporotic bone regeneration is challenging due to impaired bone formation. Tetrahedral DNA nanostructures (TDN), promising nucleic acid nanomaterials, have garnered attention for their potential in osteoporotic mandibular regeneration owing to their ability to enhance cellular activity and promote osteogenic differentiation. Osteoblasts play a critical role in bone regeneration; however, intracellular delivery of TDN into osteoblasts remains difficult. In this study, a novel osteoblast-targeted CH6 aptamer-functionalized TDN (TDN-CH6) is aimed to develop for osteoporotic mandibular regeneration. This results demonstrated that TDN-CH6 exhibits superior osteoblast specificity and efficient recruitment to bone fracture sites. Furthermore, TDN-CH6 significantly enhances cellular activity and osteogenic differentiation compared to TDN alone. Notably, Gelatin Methacryloyl (GelMA) hydrogels incorporating TDN and TDN-CH6 shows improved biological performance and are favorable for osteoporotic mandibular regeneration, suggesting that this platform represents a promising strategy for addressing complex bone defects.