ArticleBioactive materials2025
Bidirectional modulation of glycolysis using a multifunctional nanocomposite hydrogel promotes bone fracture healing in type 2 diabetes mellitus.
Article in Bioactive materials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Ternary mTOR-targeted conductive nanofibrous scaffolds with bioactive peptides orchestrate immune-metabolic-fibrotic balance for diabetic bone regeneration.Bioactive materials · 2026Article
- Glucose metabolism in osteoporosis: A potential therapeutic target (Review).International journal of molecular medicine · 2026Review
- Single cell multi-omics guided hydrogel enables closed-loop therapy for renal osteodystrophy.Nature communications · 2026Article
- A Self-Adaptive Programming Strategy Enables Local Microenvironment Modulation and Temporal Immunomodulation for Diabetic Infected Bone Regeneration.Advanced healthcare materials · 2026Article
- Hypoxia-Inducible Factor 1α in Type 2 Diabetes Mellitus: Mechanisms and Therapeutic Perspectives.Biology · 2026Review
- Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks.International journal of molecular sciences · 2026Review
- Smart immunomodulatory polysaccharide hydrogels promote diabetic bone regeneration by regulating the inflammation-angiogenesis-osteogenesis axis.Materials today. Bio · 2026Article
- High-performance hydrogels in orthopedics: Structural design, performance tuning, and clinical potential.Materials today. Bio · 2026Review
- [Effects of polyvinyl alcohol-boric acid-based functionalized hydrogels on HSFs and HaCaT cells].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2026Article
- HIF-1α at the intersection of hypoxia, ferroptosis-associated stress, and cell death crosstalk in osteomyelitis.Frontiers in cell and developmental biology · 2026Review
- HIF-1α-centered metabolic reprogramming in osteoarthritis: cell type-specific effects and intercellular crosstalk among chondrocytes, BMSCs, and macrophages.Frontiers in immunology · 2026Review
- Piezo1-Fstl1 Axis in Fracture Healing: Modulation of the Chondrocyte Inflammation-ROS-Mitochondrial Damage Cascade and Application of Smart Delivery System.International journal of biological sciences · 2026Article
- Fueling bone loss: the immunometabolic reprogramming of the bone microenvironment in diabetic osteoporosis.Frontiers in immunology · 2026Review
- Targeting innate immunity to modulate bone metabolism: a novel strategy for osteoporosis treatment.Frontiers in aging · 2026Review
- The Sirt1-Piezo1 Axis Promotes Bone Formation and Repair in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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13 authors.
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Abstract
Fracture healing in patients with type 2 diabetes mellitus (T2D) is markedly impaired, characterized by a prolonged inflammation phase and defective osteoblast differentiation at the fracture site. In this study, we identified aberrant cellular glycolysis at T2D fracture sites, with bone marrow mesenchymal stem cells (BMSCs) exhibiting suppressed glycolysis and macrophages displaying enhanced glycolysis, mediated by the dysregulation of hypoxia-inducible factor-1α (HIF-1α). To rectify these metabolic imbalances, we developed a multifunctional nanocomposite PN@MHV hydrogel. Myricitrin, a flavonoid glycoside, forms the MHV hydrogel by cross-linking with HA-PBA and PVA via hydrogen bonds, and upregulates glycolysis through HIF-1α, thus promoting osteoblast differentiation under high glucose environment. To further regulate the inflammatory microenvironment, we incorporated nanoparticles loaded with PX-478, a HIF-1α specific inhibitor, into the hydrogel, with folic acid covalently modified to target proinflammatory M1 macrophages. This PN@MHV hydrogel bidirectionally regulated glycolysis via HIF-1α, enhancing osteoblast differentiation while attenuating macrophage-mediated inflammation. Comprehensive in vitro and in vivo experiments in a T2D fracture mouse model confirmed the hydrogel's ability to improve the inflammatory microenvironment and accelerate bone healing. Our findings underscore the therapeutic potential of targeting cellular glycolysis as a promising approach for enhancing fracture healing in diabetic patients.
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