ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
A DNA Tetrahedron Delivery Asiatic Acid to Reprogram Mitochondrial Metabolism for Promoting Bone Regeneration via STAT3 Phosphorylation.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Hydrogel Implementing Drug Delivery in Cranial Bone Tissue Engineering.Journal of functional biomaterials · 2026Review
- Temporal-responsive hydrogels reprogramming energy metabolic pathway in the bone-angiogenic cascade for diabetic bone regeneration.Materials today. Bio · 2026Article
- A DNA Tetrahedron Delivery Asiatic Acid to Reprogram Mitochondrial Metabolism for Promoting Bone Regeneration via STAT3 Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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10 authors.
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Abstract
Craniofacial bone defects remain a significant clinical challenge due to the complex healing process among immune regulation, vascularization, and osteogenesis. Asiatic acid (AA), a natural pentacyclic triterpenoid, has shown promise in modulating inflammation and promoting bone repair, yet its clinical application is hampered by poor solubility, low bioavailability, and lack of targeted delivery. Here, a multifunctional hydrogel-integrated DNA nanostructure system is reported, in which AA-loaded DNA tetrahedra are embedded within a Hyaluronic Acid Methacrylate (HAMA) hydrogel（HM-TDN@AA） to enhance local retention, bioavailability, and controlled release. The HM-TDN@AA system significantly inhibited osteoclastogenesis and enhanced the osteogenic and angiogenic activity of mesenchymal stem cells and endothelial cells, respectively. In vivo implantation in a calvarial defect model revealed early enhancement of vascularization and remodeling of the immune niche, followed by robust bone formation. Transcriptomic profiling of bone tissue uncovered a metabolic reprogramming signature characterized by activation of mitochondrial oxidative phosphorylation (OXPHOS) pathways. Network pharmacology and molecular docking further identified STAT3 as a key regulatory node targeted by AA. Collectively, the findings demonstrate that the HM-TDN@AA platform orchestrates bone regeneration by simultaneously modulating inflammation, angiogenesis, and cellular metabolism. This study provides a novel strategy that integrates nanostructure-assisted drug delivery with metabolic control to enhance osteoimmune coupling and vascularized bone regeneration.
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