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Hypothesis: 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-adhesive properties able to minimise unspecific biomolecules adsorption and bacterial adhesion. Strontium-containing mesoporous bioactive glasses (Sr-MBG), which are 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 anti-adhesive abilities., Experiments: Sr-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. The final system was then characterised in terms of textural-structural properties, bioactivity, cytotoxicity, pro-osteogenic and anti-adhesive capabilities., Findings: After zwitterionization the in vitro bioactivity was maintained, as well as the ability to release Sr 2+ ions which are capable of inducing a mineralization process. Irrespective of their size, Sr-MBG particles did not exhibit any cytotoxicity in pre-osteoblastic MC3T3-E1 up to the concentration of 75 µg/mL. Finally, the zwitterionic Sr-MBGs showed a significant reduction of serum protein adhesion with respect to the pristine ones. These results open promising future expectations in the design of nanosystems which combine pro-osteogenic and anti-adhesive properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Unlabelled: Bioactive glasses have been traditionally used in the clinical practice to fill and restore osseous defects due to their unique ability to bond to host bone and stimulate new bone growth. In the last decade, a new set of bioactive glasses characterized by a highly ordered mesoporous texture has been developed and studied as a smart platform for the controlled release of biomolecules, in situ therapy and regenerative applications. This review points out the great potential carried by hierarchical bioactive glass scaffolds that exhibit pore scales from the meso- to the macro-range, and their impact in the broad field of tissue engineering, including the emerging applications in contact with soft tissues and diagnostics. Recent advances in the preparation methods of these multiscale constructs (e.g. mono- or multi-phase scaffolds, fibrous meshes, coated systems, porous nanospheres, and composites) are examined, along with their strengths and weaknesses. A bright future is expected for hierarchical systems based on biocompatible mesoporous materials as they can provide a unique set of functionalities, including enhanced bioactivity, local release of ions and drugs to elicit specific therapeutic effects (improved osteogenesis and angiogenesis, antibacterial properties), and implant/drug tracking, which were unthinkable when research on bioactive glasses began., Statement of Significance: The advent of mesoporous bioactive glasses led to the birth of a new class of multifunctional biomaterials that have been proposed as smart platforms for local drug release and bone regeneration. Furthermore, mesoporous materials have been recently employed in the development of hierarchical macro-mesoporous scaffolds, composites and implantable systems. This reviews summarizes the latest applications of these multiscale biomaterials in tissue engineering, including the emerging applications in contact with soft tissues and diagnostics. The preparation methods, current uses and potential of these constructs and systems are examined and critically discussed to provide a useful, up-to-date contribution to the scientists working in the field., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: Coupling the potential for bone regeneration and the ability for in situ controlled drug release in a single device is a challenging field of research in bone tissue engineering; in an attempt to pursue this aim, mesoporous bioactive glass (MBG) membranes belonging to the SiO2-P2O5-CaO ternary system were produced and characterized., Methods: The glass was synthesized via a sol-gel route coupled with an evaporation-induced self-assembly process by using a non-ionic block co-polymer as a mesostructure former. MBG structure and morphology, as well as mesopores size and shape, were investigated by x-ray diffraction, transmission electron microscopy, and N2 adsorption-desorption measurements. In vitro bioactivity was investigated by soaking MBG membranes in simulated body fluid (SBF) for different time frames. Ibuprofen was encapsulated into MBG pores and drug release kinetics in SBF were assessed. Biological tests by using SAOS-2 cells were performed to assess the material cytocompatibility., Results: The material revealed significant ability to induce hydroxyapatite formation on its surface (bioactivity). Drug release kinetics in SBF are very similar to those obtained for mesoporous silica having mesopore size comparable to that of the prepared MBG (∼5 nm). No evidence of cell viability depression was detected during in vitro culture, which demonstrates the good biological compatibility of the material., Conclusions: The easiness of tailoring and shaping, the highly bioactive and biocompatible behavior, and the drug uptake/release ability of the prepared materials may suggest their use as "smart" multifunctional grafts for bone reconstructive surgery.