Additive manufacturing and in vitro characterization of scaffolds consisting of PCL/P2O5-free bioactive glasses composites with angiogenic and osteogenic potential

The development of scaffolds with osteogenic and angiogenic properties represents an attractive strategy for regenerating large bone defects. This study describes the fabrication and characterization of bioactive glass-based composite scaffolds for bone regeneration applications. Scaffolds comprising polycaprolactone (PCL) and two different bioactive glasses (BGs), derived from white sand (BG-WS) and yellow sand (BG-YS), at an 80:20 wt% ratio were fabricated with a star-shaped pore geometry. Chemical characterization confirmed the presence of characteristic groups from PCL and BGs. The incorporation of BGs led to increased compressive moduli in the composites compared to PCL scaffolds only. Dissolution products, particularly from PCL/BG-YS, promoted enhanced vascular pattern formation of human umbilical endothelial vein cells (HUVECs) co-cultured indirectly with human mesenchymal stromal cells (hMSCs). Direct culture of hMSCs on PCL/BG-WS and PCL/BG-YS composite scaffolds resulted in greater VEGFA production compared to PCL scaffolds alone. The expression of the early osteogenic marker RUNX2 was upregulated on day 7 in response to both composite scaffolds, while ALPL expression increased only with the PCL/BG-WS scaffolds on day 28. Additionally, late osteogenic gene markers (COL1A1 and OCN) were both upregulated on day 28 in PCL/BG-WS scaffolds. Lastly, the measurement of analytes secreted by hMSCs showed higher secretion levels on day 7 than 28, with PCL scaffolds yielding higher concentrations of IL-10, TNF-α, and CCL2 than composite scaffolds. Overall, both PCL/BG-WS and PCL/ BG-YS scaffolds demonstrated osteogenic, angiogenic, and potential immunomodulatory properties. Notably, PCL/BG-WS exhibited the strongest osteogenic responses, which may be attributed to its Ti4+ ion content, highlighting the critical role of BG composition in modulating the biological performance of the composites. The findings of this study indicate that combining naturally-derived P2O5-free BGs with PCL to fabricate 3D composite scaffolds enhances osteogenic and angiogenic properties of the final constructs, emphasizing their potential in bone regeneration.