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.

Biomaterials used in regenerative medicine should be able to support and promote the growth and repair of natural tissues. Bioactive glasses (BGs) have a great potential for applications in bone tissue engineering [1, 2]. As it is well known BGs can bond to host bone and stimulate bone cells toward osteogenesis. Silicate BGs, e.g. 45S5 Bioglass® (composition in wt.%: 45 SiO₂, 6 P₂O₅, 24, 5 Na₂O and 24.5 CaO), exhibit positive characteristics for bone engineering applications considering that reactions on the material surface induce the release of critical concentrations of soluble Si, Ca, P and Na ions, which can lead to the up regulation of different genes in osteoblastic cells, which in turn promote rapid bone formation. BGs are also increasingly investigated for their angiogenic properties.

This presentation is focused on cell behavior of osteoblast-like cells and osteoclast-like cells on BGs with varying sample geometry (including dense discs for material evaluation and coatings of highly porous Al₂O₃-scaffolds as an example of load-bearing implants). To obtain mechanically competent porous samples with trabecular architecture analogous to those of cancellous bone, in this study Al₂O₃ scaffolds were fabricated by the well-known foam replication method and coated with Bioglass® by dip coating.

The resulted geometry and porosity were proven by SEM and μCT. Originating from peripheral blood mononuclear cells formed multinucleated giant cells, i.e. osteoclast-like cells, after 3 weeks of stimulation with RANKL and M-CSF. Thus, the bioactive glass surface can be considered a promising material for bone healing, providing a surface for bone remodeling. Osteoblast-like cells and bone marrow stromal cells were seeded on dense bioactive glass substrates and coatings showing an initial inhibited cell attachment but later a strong osteogenic differentiation. Additionally, cell attachment and differentiation studies were carried out by staining cytoskeleton and measuring specific alkaline phosphatase activity. In this context, 45S5 bioactive glass surfaces can be considered a highly promising material for bone tissue regeneration, providing very fast kinetics for bone-like hydroxyapatite formation (mineralization). Our examinations revealed good results in vitro for cell seeding efficacy, cell attachment, viability, proliferation and cell penetration onto dense and porous Bioglass®-coated scaffolds.

Recent in vivo investigations [3] have revealed also the angiogenic potential of bioactive glass both in particulate form and as 3D scaffolds confirming the high potential of BGs for bone regeneration strategies at different scales. Implant surfaces based on bioactive glasses offer new opportunities to develop these advanced biomaterials for the next generation of implantable devices and tissue scaffolds with desired tissue-implant interaction.