Thermally stable strontium- and magnesium-enriched bioactive glass scaffolds promote bone regeneration and angiogenesis: An in vivo comparative study with 45S5

The development of biomaterials to actively support both bone formation and vascularization represents a key challenge in regenerative medicine. Two novel bioactive glasses, Bio_MS and BGMS10, enriched with therapeutic ions such as strontium and magnesium and characterized by high thermal stability, were fabricated into porous scaffolds using the foam replica method and compared to the conventional 45S5 Bioglass®. The materials were evaluated for their ionic release, angiogenic potential (using the chorioallantoic membrane-CAM assay) and bone regenerative capacity in vivo (using rabbit models with femur/tibia defects). Ion release analyses revealed controlled and sustained release of biologically active ions (Ca, Mg, Sr, Si) from Bio_MS and BGMS10 scaffolds. By CAM assay, both the novel scaffolds enhanced vessel density and branching, indicating a good pro-angiogenic effect. After 60 days of implantation, SEM/X-EDS and histomorphometric analyses demonstrated extensive new bone formation and effective osteo–scaffold coupling for all three BGs, even if Bio_MS scaffold showed the highest affinity index. Histological observations confirmed abundant osteoblast laminae and limited osteoclastic activity around Bio_MS, whereas BGMS10 samples showed higher osteoclast presence, possibly due to their elevated Mg release. In summary, these results showed that all bioactive glasses show no significant differences in terms of osteoconductive potential, although Bio_MS, having faster ionic dissolution and higher affinity index than the others, seems in a more advanced stage of dissolution, inducing early osteogenesis, as evidenced by the presence of abundant osteoblastic laminae close to its surface; these features make it a strong candidate for bone-defect repair and broader regenerative medicine applications.