Polymer-Bioactive Glass Composite Scaffolds for Bone Regeneration: Incorporating P2o5-Free Bioactive Glasses With Osteogenic and Angiogenic Properties

The continuing aging of the population and the increasing prevalence of diseases affecting the musculoskeletal system are driving research into the development of advanced implantable materials. Among these, bioactive glasses (BGs) from the SiO 2 -CaO-Na 2 O system have shown promise for promoting bone regeneration due to their osteogenic and angiogenic properties. In this study, two BG formulations were combined with polycaprolactone (PCL) and additively manufactured into 3D porous scaffolds for bone regeneration applications. The resulting composite scaffolds (PCL/BG-WS and PCL/BG-YS, 80:20 wt%) were characterized and evaluated for their angiogenic and osteogenic properties in vitro . Additionally, the influence of the scaffolds on the paracrine function of human mesenchymal stromal cells (hMSCs) was assessed. Characterization confirmed the expected presence of both PCL and BG components. Mechanical testing showed that incorporating BG particles increased the compressive modulus compared to PCL-only scaffolds. In vitro , the dissolution products from the composite scaffolds containing BGs, particularly PCL/BG-YS, enhanced vascular pattern formation of human umbilical vein endothelial cells (HUVECs) in an indirect co-culture setup. Furthermore, direct culture of hMSCs on the PCL/BG-WS and PCL/BG-YS composite scaffolds resulted in greater VEGFA production compared to PCL scaffolds alone. The addition of both BG-WS and BG-YS to PCL promoted upregulation of RUNX2 expression on day 7 in hMSC cultures, while ALPL expression was upregulated only in PCL/BG-WS composite scaffolds on day 28. However, ALP activity was lower on composite scaffolds than on PCL-only scaffolds. Regarding late osteogenic gene markers, COL1A1 and OCN were both upregulated on day 28 in PCL/BG-WS scaffolds. Finally, measurements of cytokine secretion by hMSCs showed higher overall concentrations on day 7 compared to day 28, with PCL scaffolds yielding higher concentrations of IL-10, TNF-α, and CCL2 than the composite scaffolds. These results highlight the potential of BG-reinforced scaffolds for promoting both angiogenesis and osteogenesis in bone tissue engineering.