Promising work on bioactive glasses (BAGs) in bone defect regeneration has led to their clinical implementation. However, the effects of the ionic dissolution products of different types and the physical interaction modalities of BAGs on the behavior and function of mesenchymal stromal cells (MSCs) of human patients have not received sufficient attention. Recently, we showed that the in vitro response of hMSC to micron-sized, monodispersed BAGs is dependent on dosage, composition, and mode of interaction¹. Two commercially available and widely used types of BAGs, namely the silicate BAGs 45S5 and 1393, were used to study hMSC cell behavior. Interestingly, exposure to 1393 BAG resulted in superior metabolic activity, proliferation, and cell spreading compared to 45S5 BAG in similar dosage, suggesting that additional cellular functions could also be differentially modulated by both glasses¹. In the context of bone regeneration, the hMSCs’ potential to secrete angiogenic factors as well as deposit mineralized matrix upon exposure to BAG dissolution products was investigated in the present study. Aside from dose-dependent effects of both glasses, 45S5 BAG induced a significant pro-angiogenic response, demonstrated by robust tube formation in HUVECs in the presence of MSC conditioned media. 1393 BAG, on the other hand, stimulated osteogenesis by upregulating osteogenic gene expression and mineralized matrix deposition. Based on these results, combining the pro-angiogenic 45S5 BAG and the pro-osteogenic 1393 BAG might be an attractive strategy to target the multiple processes underlying bone regeneration. These results highlight how different BAGs can be utilized to promote MSC-mediated bone regeneration.

The bone infection osteomyelitis (typically Staphylococcus aureus) requires a multistep treatment process including: surgical debridement, long-term systemic high-dose antibiotics, and often bone grafting. With antibiotic resistance becoming increasingly concerning, alternative approaches are urgently needed. Herein, we develop a one-step treatment for osteomyelitis that combines local, controlled release of non-antibiotic antibacterials (copper) within a proven regenerative scaffold. To maximise efficacy we utilised bioactive glass – an established material with immense osteogenic capacity – as a copper ion delivery reservoir. Copper ions have also been shown to stimulate angiogenesis and induce MSC differentiation down an osteogenic lineage. To eliminate grafting requirements, the copper-doped BG was incorporated into our previously developed collagen scaffolds to produce multifunctional antibacterial, osteogenic, and angiogenic scaffolds. Scaffolds were fabricated by freeze-drying a co-suspension of collagen and bioactive glass particles (+/− copper doping, referred to as CuBG and BG, respectively) at a range of different concentrations (0–300% w/w bioactive glass/collagen). Scaffolds demonstrated a 2.7-fold increase in compressive modulus (300% CuBG vs. 0%; p≤0.01), whilst maintaining >98% porosity. The 300% CuBG scaffolds showed significant antibacterial activity against Staphylococcus aureus (p≤0.001). In terms of osteogenesis, both 100% and 300% CuBG scaffolds increased cell-mediated calcium deposition on the scaffolds at day 14 and 28 (p≤0.05 and p≤0.001), as confirmed by alizarin red staining. 100% CuBG scaffolds significantly enhanced angiogenesis by increased tubule formation (p≤0.01) and VEGF protein production (p≤0.001) (all ≥n=3). In summary, this single-stage, off-the-shelf treatment for osteomyelitis shows potential to minimise bone grafting and antibiotic dependence, while reducing hospital stays and costs.