No abstract

Bioactive glasses (BAG) are used as bone-graft substitutes in orthopaedic surgery. A specific BAG scaffold was developed by sintering BAG-S53P4 granules. It is hypothesised that this scaffold can be used as a bone substitute to fill bone defects and induce a bioactive membrane (IM) around the defect site. Beyond providing the scaffold increased mechanical strength, that the initial inflammatory reaction and subsequent IM formation can be enhanced by coating the scaffolds with poly(DL-lactide-co-glycolide) (PLGA) is also hypothesised. To study the immunomodulatory effects, BAG-S53P4 (± PLGA) scaffolds were placed on monolayers of primary human macrophage cultures and the production of various pro- and anti-inflammatory cytokines was assessed using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and ELISA. To study the osteogenic effects, BAG-S53P4 (± PLGA) scaffolds were cultured with rabbit mesenchymal stem cells and osteogenic differentiation was evaluated by RT-qPCR and matrix mineralisation assays. The scaffold ion release was quantified and the BAG surface reactivity visualised. Furthermore, the pH of culture media was measured. BAG-S53P4 scaffolds had both anti-inflammatory and osteogenic properties that were likely attributable to alkalinisation of the media and ion release from the scaffold. pH change, ion release, and immunomodulatory properties of the scaffold could be modulated by the PLGA coating. Contrary to the hypothesis, the coating functioned by attenuating the BAG surface reactions and subsequent anti-inflammatory properties, rather than inducing an elevated inflammatory response compared to BAG-S53P4 alone. These results further validated the use of BAG-S53P4 (± PLGA) scaffolds as bone substitutes and indicate that scaffold properties can be tailored to a specific clinical need.

We studied how in vitro reactions affect long-term biochemical and mechanical properties of porous tissue engineering scaffolds based on two bioactive glasses and accordingly their potential suitability for treating critical-size load-bearing bone defects. Granules of bioactive glass S53P4 and S59 were used to sinter the porous scaffolds. The sintering variables for mechanically durable scaffolds were initially selected according to the thermal behaviour of the glasses during heating. The S53P4 and S59 scaffolds were further divided into the following three groups: uncoated scaffolds, poly(dl-lactide-co-glycolide) (PLGA) coated scaffolds, and scaffolds coated with a mixture of PLGA and powdered S53P4. The purpose of the coating is to enhance mechanical abilities and to induce a membrane rich in growth factors surrounding the BAG implant. Characterization of the scaffolds included water absorption, pH, ion release, reaction layer formation, and compressive strength. Polymer coatings with powdered S53P4 absorbed more water than pure polymer coatings. The pH of the immersion solution increased more upon immersion of the uncoated scaffolds. No marked differences were seen between the coated scaffolds. During the 28-day in vitro immersion, the Ca-ion concentration initially increased for non-coated S53P4 scaffolds, followed by a slight increase starting at 14 days for all S53P4-based scaffolds and S59-PLGA scaffolds. The lowest P species concentration was observed for uncoated S53P4 scaffolds. The polymer coatings hindered the dissolution of Si-species from the scaffolds. Thicker calcium phosphate layers were identified at the uncoated scaffolds, suggesting a higher bioactivity. In contrast, the polymer coatings enhanced the compressive strength of the scaffolds. The results reflect the impact of glass composition and polymer coating on the chemical and physical properties of scaffolds, emphasizing the requirements in clinical applications for critical load-bearing bone defects. Graphical Abstract