PCL/SSAD bioactive scaffolds loaded aminoguanidine-functionalized MSN for enhanced diabetic bone regeneration

Diabetic bone regeneration is hindered by factors such as hyperglycemia, accumulation of advanced glycation end products (AGEs), and inflammation, presenting a significant clinical challenge. In this study, functionalized mesoporous silica nanoparticles (MSN) loaded with aminoguanidine (AG, MSN@AG) were incorporated into skin secretion of Andrias davidianus (SSAD) and poly (ε-caprolactone) (PCL) electrospun fibers, creating a bioactive scaffold (SSAD/PCL/MSN@AG, SPMA) that provides sustained release of AG and osteogenic factors. It effectively inhibited free radical generation, AGEs toxicity and inflammation, and recruited bone marrow mesenchymal stem cells (BMSCs) with excellent biocompatibility and better BMSCs viability, osteogenic differentiation, and mineralization under high-glucose microenvironment in vitro . Furthermore, in vivo evaluation in a diabetic mice skull defect model showed that the SPMA scaffold ameliorated local inflammation and improved vascularization, significantly accelerating new bone formation and defect repair. This study provides a simple preparation of PCL pro-osteogenic scaffolds with bioactive, hydrophilic and altering functions of the high-glucose microenvironment, which offers a new repair strategy for diabetic bone defects.