Over the recent years, mesoporous bioactive glasses (MBGs) gained interest as bone regeneration systems, due to their excellent bioactivity and ability to release therapeutic molecules. In order to improve the bone regeneration ability of MBGs, the incorporation of Sr2+ ions, due to its recognized pro-osteogenenic potential, represents a very promising strategy. In this study, MBGs based on the SiO2–CaO system and containing different percentages (2 and 4 mol %) of strontium were prepared by two synthesis methods, in the form of microspheres and nanoparticles. Sr-containing MBGs were characterized by FE-SEM, XRD and N2 adsorption/desorption analysis. The in vitro bioactivity in SBF resulted excellent. The assessment of fibroblast cell (line L929) viability showed that Sr-containing MBGs were biocompatible both in form of micro- and nanoparticles. The osteogenic response of osteoblast-like SAOS-2 cells was investigated by analysing the expression of GAPDH, COL1a1, RANKL, SPARC, OPG and ALPL genes, as cell differentiation markers. The results indicate that the incorporation of Sr into MBG is beneficial for bone regeneration as promotes a pro-osteogenic effect, paving the way to the design of advanced devices enabled by these nanocarriers also in combination with drug release, for the treatment of bone pathologies, particularly in patients with osteoporosis.

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Mini-invasively injectable hydrogels are widely attracting interest as smart tools for the co-delivery of therapeutic agents targeting different aspects of tissue/organ healing (e.g., neo-angiogenesis, inflammation). In this work, copper-substituted bioactive mesoporous glasses (Cu-MBGs) were prepared as nano- and micro-particles and successfully loaded with ibuprofen through an incipient wetness method (loaded ibuprofen approx. 10% w/w). Injectable hybrid formulations were then developed by dispersing ibuprofen-loaded Cu-MBGs within thermosensitive hydrogels based on a custom-made amphiphilic polyurethane. This procedure showed almost no effects on the gelation potential (gelation at 37 °C within 3–5 min). Cu2+ and ibuprofen were co-released over time in a sustained manner with a significantly lower burst release compared to MBG particles alone (burst release reduction approx. 85% and 65% for ibuprofen and Cu2+, respectively). Additionally, released Cu2+ species triggered polyurethane chemical degradation, thus enabling a possible tuning of gel residence time at the pathological site. The overall results suggest that hybrid injectable thermosensitive gels could be successfully designed for the simultaneous localized co-delivery of multiple therapeutics.

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The treatment of bone fractures still represents a challenging clinical issue when complications due to impaired bone remodelling (i.e. osteoporosis) or infections occur. These clinical needs still require a radical improvement of the existing therapeutic approach through the design of advanced biomaterials combining the ability to promote bone regeneration with anti-fouling/anti-adhesive properties able to minimise unspecific biomolecules adsorption and bacterial adhesion. Strontium-containing mesoporous bioactive glasses (Sr-MBG), able to exert a pro-osteogenic effect by releasing Sr 2+ ions, have been successfully functionalised to provide mixed-charge (-NH 3 ⊕ /-COO ⊝ ) surface groups with low-fouling abilities. ExperimentsSr-MBG have been post-synthesis modified by co-grafting hydrolysable short chain silanes containing amino (aminopropylsilanetriol) and carboxylate (carboxyethylsilanetriol) moieties to achieve a zwitterionic zero-charge surface and then characterised in terms of textural-structural properties, bioactivity, cytotoxicity, pro-osteogenic and low-fouling capabilities. FindingsAfter zwitterionization the in vitro bioactivity is maintained, as well as the ability to release Sr 2+ ions capable to induce a mineralization process. Irrespective of their size, Sr-MBG particles did not exhibit any cytotoxicity in preosteoblastic MC3T3-E1 up to the concentration of 75 µg/mL. Finally, the zwitterionic Sr-MBGs show a significant reduction of serum protein adhesion with respect to pristine ones. These results open promising future expectations in the design of nanosystems combining pro-osteogenic and anti-adhesive properties.