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This study constructed a multifunctional hydrogel integrated DNA nanostructure system (HM-TDN@AA), by combining DNA tetrahedrons loaded with Asian acid (AA) with hyaluronic acid methacrylate hydrogel, to optimize the delivery efficiency of AA. By regulating inflammatory responses, angiogenesis and cell metabolism, it achieved synergistic promotion of bone regeneration. Research Background
The acid in Asia has problems such as low solubility, insufficient bioavailability and lack of targeting ability. Moreover, the bone regeneration process involves complex and coordinated interactions among various aspects such as inflammation regulation, vascular formation and cell metabolism. The current solutions are unable to achieve multi-dimensional precise regulation.
Main Content
The HM-TDN@AA composite system was designed and constructed, integrating DNA tetrahedral-mediated drug delivery with metabolic regulation. It targeted the key regulatory node of STAT3. By inhibiting osteoclast formation, enhancing the osteogenic activity of mesenchymal stem cells, and increasing the angiogenic activity of endothelial cells, it reshaped the immune niche and activated the mitochondrial oxidative phosphorylation pathway, coordinating the multi-step regulation related to bone regeneration. Research Design
Using Asian acid (AA), DNA tetrahedron, and hydroxyethyl methacrylate hyaluronic acid (HAMA) hydrogel as core materials, a composite delivery system was constructed to focus on the remodeling of the immune microenvironment, the regulation of cell activity, and the activation of metabolic pathways during bone regeneration. Through multi-dimensional mechanisms, bone regeneration promotion was achieved in a coordinated manner. Result
This composite system effectively enhances the local retention ability and bioavailability of AA, achieving controlled drug release; successfully inhibits osteoclast formation, significantly enhances the osteogenic activity of mesenchymal stem cells and the angiogenic activity of endothelial cells; effectively reshapes the immune niche, activates mitochondrial oxidative phosphorylation-related metabolic pathways, and achieves coordinated regulation of inflammation, angiogenesis and cellular metabolism, providing strong support for bone regeneration.
Thought extension
It provides a new direction combining nanodelivery technology and metabolic regulation for complex regulatory problems in scenarios such as craniofacial bone defect healing, offering new ideas and references for research in bone-immune coupling and vascularized bone regeneration fields.
Original source:
1. Journal name: Advanced Science (Impact factor: 14.1) 2. Publication date: 2025-12-19 3. DOI: 10.1002/advs.202518796 (original link: https://doi.org/10.1002/advs.202518796) 4. Authors: Yiwen Huang, Yiming Zhang, Yisheng Feng, Qixiang Yang, Beiyuan Gao, Haiyang Xu, Cheng Huang, Kaili Lin, Yuanzhi Xu, Peiqi Zhu
