SRS139 - PCL-cobalt bioactive glass composite scaffolds for stratified bone regeneration

Abstract Background Critical-sized bone defects (CSDs) are difficult to treat, particularly in diabetic patients, where impaired angiogenesis, chronic inflammation, and abnormal bone turnover hinder healing. Standard techniques such as autologous bone grafting and the induced membrane method are limited by donor morbidity, graft resorption, and multiple procedures. Bioactive glass (BG, for example 45S5) promotes osteogenesis via ionic release (Ca²⁺, Si⁴⁺, PO₄³⁻). Cobalt silicate bioactive glass (CoSiBG) may enhance this by stabilising hypoxia-inducible factor-1α (HIF-1α), thereby upregulating VEGF and supporting angiogenesis. Aims This study evaluated whether incorporating CoSiBG into polycaprolactone (PCL) scaffolds altered physicochemical, osteogenic, and angiogenic performance compared with 45S5 and controls. Methods PCL scaffolds with 45S5 or CoSiBG (5–50 wt%) were fabricated via solvent casting. Physicochemical properties were characterised by SEM, rheology, contact angle, dissolution, and degradation testing. Human bone marrow mesenchymal stem cells were cultured for 1–7 days. Proliferation (PrestoBlue, PicoGreen), osteogenesis (ALP activity), and angiogenesis (VEGF secretion) were quantified and normalised to DNA. Results BG incorporation increased ion release dose-dependently, elevating pH and accelerating degradation. CoSiBG released Co²⁺ at concentrations consistent with hypoxia-mimetic activity. Low-dose CoSiBG (5 wt%) produced the highest VEGF/DNA ratios without impairing viability. ALP activity was comparable across 45S5 and CoSiBG groups, confirming preserved osteogenic potential. Conclusions PCL–CoSiBG composites provided controlled ion release, stimulated pro-angiogenic signalling, and maintained osteogenesis. Optimised low-dose formulations show promise for addressing impaired vascularisation and bone regeneration in CSDs, supporting their progression to translational studies in high-risk patients, particularly those with diabetes.