Endogenous dysregulated energy and amino acid metabolism delay scaffold-guided large volume bone regeneration in a diabetic rat model with Leptin receptor deficiency.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Scaffold-guided bone regeneration (SGBR) offers a promising solution for treating large-volume bone defects. However, its efficacy in compromised healing environments, such as those associated with metabolic conditions like Type 2 Diabetes (T2D), remains poorly understood. This study evaluates the potential of 3D-printed polycaprolactone (PCL) scaffolds for large-volume bone regeneration in preclinical models simulating T2D-induced metabolic challenges. Our results reveal that scaffolds alone are insufficient to overcome the metabolic barriers to effective bone regeneration. Metabolomic analysis of regenerating tissue identified significant disruptions in key metabolic pathways involved in energy production and amino acid synthesis in T2D rats compared to controls. Notably, aconitic acid, ornithine, and glycine levels were elevated in non-diabetic conditions, whereas phosphoenolpyruvate was markedly increased under T2D conditions. Secondary harmonic generation (SHG) imaging further demonstrated impaired collagen organization within T2D regenerating tissue, correlating with disrupted collagen synthesis critical for bone matrix formation. In vitro, the exogenous supplementation of alpha-ketoglutarate (α-KG)-a crucial citric acid cycle intermediate-enhanced mineralized tissue formation in human adipose-derived mesenchymal stem cells (hAdMSCs) from T2D donors, achieving levels supe

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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