3D-Printed Alginate Scaffolds Incorporated with Synergistic Strontium/Magnesium -Doped Bioglass Nanoparticles for Bone Regeneration: An In Vivo Evaluation in Rabbit Cranial Defects

Nonunion fractures remain a major orthopedic challenge, highlighting the need for improved bone tissue engineering (BTE) strategies. This study hypothesized that incorporating Sr/Mg-doped 58S bioglass nanoparticles into 3D-printed alginate (Alg) scaffolds would improve their physicochemical, mechanical, and biological properties and enhance bone regeneration. Structural characterization showed that Sr/Mg-doping reduced bioglass size and produced interconnected porous scaffolds. Under wet conditions, Alg scaffold incorporating 2.5%Sr/Mg-doped 58S bioglass showed the highest Young’s modulus (0.4356 ± 0.0244 MPa), whereas under dry conditions, the Alg scaffold incorporating 5%Sr/Mg-doped 58S bioglass achieved the highest value (0.1945 ± 0.0519 MPa). In vitro studies demonstrated biocompatibility and enhanced cell attachment and proliferation. After 7 days, Alg scaffold incorporating 5%Sr/Mg-doped 58S bioglass showed the highest cell viability: 101.09 ± 7.4% for L929 fibroblasts and 82.38 ± 3.4% for human adipose-derived mesenchymal stem cells (hADSCs). In a rabbit critical-sized cranial defect model, this scaffold achieved the highest bone healing rate (53.42%), reducing the defect volume to 6.65 mm³. Histological analyses confirmed reduced necrosis and inflammation, increased collagen deposition, and enhanced new bone formation. Overall, 5% Sr/Mg doping improved scaffold mechanical and biological performance, supporting its potential for BTE while maintaining favorable cellular responses and promoting bone regeneration.