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Bone repair in elderly patients poses a huge challenge due to the age-related progressive decline in regenerative abilities attributed to the senescence of bone marrow stem cells (BMSCs). Bioactive scaffolds have been applied in bone regeneration due to their various biological functions. In this study, we aimed to fabricate functionalized bioactive scaffolds through loading osteoinductive extracellular vesicles (OI-EVs) based on mesoporous bioactive glass (MBG) scaffolds (1010 particles/scaffold) and to investigate its effects on osteogenesis and senescence of BMSCs. The results suggested that OI-EVs upregulate the proliferative and osteogenic capacities of senescent BMSCs. More importantly, The results showed that loading OI-EVs into MBG scaffolds achieved better bone regeneration. Furthermore, OI-EVs and BMSCs RNAs bioinformatics analysis indicated that OI-EVs play roles through transporting pivotal lncRNA acting as a "sponge" to compete with Mob3a for miR-1843a-5p to promote YAP dephosphorylation and nuclear translocation, ultimately resulting in elevated proliferation and osteogenic differentiation and reduced senescence-related phenotypes. Collectively, these results suggested that the OI-EVs lncRNA ceRNA regulatory networks might be the key point for senescent osteogenesis. More importantly, the study indicated the feasibility of loading OI-EVs into scaffolds and provided novel insights into biomaterial design for facilitating bone regeneration in the treatment of senescent bone defects. Constructing OI-EVs/MBG delivering system and verification of its bone regeneration enhancement in senescent defect repair. Aging bone repair poses a huge challenge due to the age-related progressive degenerative decline in regenerative abilities attributed to the senescence of BMSCs. OI-EVs/MBG delivering system were expected as promising treatment for senescent bone repair, which could provide an effective strategy for bone regeneration in elderly patients. Clarification of potential OI-EVs lncRNA ceRNA regulatory mechanism in senescent bone regeneration OI-EVs play important roles through transferring lncRNA-ENSRNOG00000056625 sponging miR-1843a-5p that targeted Mob3a to activate YAP translocation into nucleus, ultimately alleviate senescence, promote proliferation and osteogenic differentiation in O-BMSCs, which provides theoretical basis for EVs-mediated therapy in future clinical works. [Display omitted] [ABSTRACT FROM AUTHOR]

Mesoporous bioactive glass nanoparticles (MBGNPs) containing therapeutic ions have shown significant promise in the realm of hard and soft tissue repair and regeneration, owing to their multifunctional biological properties. In this study, gallium-incorporated silica-based gallium incorporated MBGNPs (Ga-MBGNPs) with fixed amount of Li 2 O (8 mol %) were synthesized using an emulsion-assisted sol-gel method. The impact of Ga 2 O 3 integration into the silicate glass network was evaluated by investigating the microtextural properties. The results confirmed the production of spherical-shaped, nano-sized, amorphous particles with an enhanced specific surface area and ordered hexagonal meso-porosity (10–20 nm) in the developed Ga-MBGNPs. The in vitro bioactivity, assessed through hydroxyapatite (HAp) layer formation in simulated body fluid (SBF), over varying time intervals (0, 1, 3, 7, 14 & 21 days), revealed pronounced formation of short rod-like carbonated HAp with increasing immersion time and Ga3+ content in all glasses. However, a delayed apatite formation was observed for composition-dependent Ga-4 and Ga-5 MBGs during the initial incubation periods (1, 3, and 7 days). Further, the presence of Li + ions along with Ga3+ enhanced the apatite deposition when compared with the only Ga3+ inclusion. Evaluation of degradation rate and pH values indicated enhanced apatite formation with lower Ga ion content, while a slight reduction was noted with higher Ga ion content, attributable to the presence of reactive Si–O–Si bonds. Furthermore, analysis using a Zeta potential analyzer confirmed the dispersibility and bioreactivity of all glass powders owing to their higher negative surface charge. Moreover, Ga-MBGNPs exhibited notable antimicrobial effects against both E. coli and S. aureus bacteria due to the release of Ga3+ ions. Overall, the findings suggest that the incorporation of Ga in MBGNPs renders them potential multifunctional candidates for expediting the healing of bone tissue injuries in biomedical applications. [Display omitted] • Synthesis of Ga 2 O 3 mixed MBGN particles by the emulsion-assisted sol-gel. • SAXRD validates the ordered hexagonal mesoporosity of Ga-MBGNPs. • Reported high specific surface area with increased content of Ga 2 O 3. • Enhanced HCA mineralization over the MBG surfaces with immersion time. • Ga3+ ions in silica MBGs demonstrate substantial antimicrobial efficacy. [ABSTRACT FROM AUTHOR]

The role of osteoimmunomodulation in orthopedic biomaterials has been demonstrated to be crucial in the regulation of bone repair and regeneration. Macrophages, the primary effector cells in the immune response to biomaterials, are highly heterogeneous and plastic, making them a prime target for immunomodulation. Mesoporous bioactive glass (MBG) is widely recognized for its biocompatibility, osteoconductivity, osteoinductivity, and immunomodulatory properties. However, the impact of MBG content on macrophage response remains unclear. To fill this knowledge gap, we designed a series of hierarchical PLGA-based composite scaffolds with varying MBG contents (0%, 10%, 20% and 40%, named as P, P10M, P20M and P40M, respectively) to investigate the osteoimmunomodulatory effects of these scaffolds. Our findings indicated that the P10M scaffolds showed a faster immune response in the early stage and exhibited superior ability to shift the pro-inflammatory immune microenvironment towards an anti-inflammatory state in the later stage, thereby enhancing the angiogenic potential of HUVECs and the osteogenic capacity of BMSCs. Furthermore, the in vivo implantation demonstrated that the immune microenvironment induced by P10M scaffolds facilitated optimal neovascularization and ectopic bone formation. These findings establish a theoretical foundation for the development of bone immunoregulatory biomaterials doped with MBG, which can effectively promote bone repair and regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The control of bacterial infections is of particular importance in the field of tissue engineering. Recently, much attention has been addressed toward the use of mesoporous bioactive glasses (MBGs) for antibacterial strategies, primarily because of their capability of acting as carriers for the local release of antimicrobial agents. The incorporation of antibacterial metallic ions including silver (Ag+), zinc (Zn2+), copper (Cu+ and Cu2+), cerium (Ce3+ and Ce4+), and gallium (Ga3+) cations into the MBG structure and their controlled release is proposed as one of the most attractive strategies for inhibiting bacterial growth and reproduction. Moreover, the possibility of loading and delivering various antibacterial biomolecules (e.g., antibiotics) through the porous structure of MBGs makes them as ideal candidates for antibacterial applications. In this review, we aim to present a comprehensive evaluation of MBG potential regarding antibacterial activities. For this purpose, different types of antibacterial ion-doped and drug-loaded MBGs are introduced and discussed in the light of existing knowledge, along with the significant challenges ahead. Statement of significance Prevention and treatment of infections is one of the today's greatest challenges in medical sciences, also considering the well-known issues related to increased bacterial resistance to antibiotics. The advent of mesoporous glasses led to the birth of a new class of multifunctional biomaterials acting as bioactive platforms for the local release of organic or inorganic agents eliciting an antimicrobial effect. This reviews summarizes the state of the art of MBGs in this field, highlighting the latest evolutions and the specific role played by metallic antimicrobial ions that can be incorporated in the glass composition and then properly released. Perspective for tissue engineering applications are also discussed to provide an up-to-date contribution that is useful to both experienced scientists and early-stage researchers. [ABSTRACT FROM AUTHOR]

Abstract: Hierarchically mesoporous bioactive glass (HMBG) was prepared using pine pollen as the biological template for lysozyme immobilization via intermolecular interactions. Effects of the initial concentration of lysozyme, pH, stirring speed (rpm), and temperature on lysozyme adsorption were investigated. The results showed that HMBG could immobilize lysozyme efficiently, and a maximum adsorption capacity of 648 ± 5.1 mg g−1 was achieved at the optimum immobilization conditions. Moreover, it was found that the adsorption process fit well with the Langmuir isothermal model. Morphology and pore structure of prepared HMBG were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-Ray diffraction (XRD), and nitrogen adsorption-desorption measurements. Lysozyme immobilization was verified by Fourier transform infrared (FTIR) spectroscopy. In addition, no change in the secondary structure of lysozyme during the adsorption/desorption process was demonstrated by UV-visible spectroscopy (UV-Vis), molecular fluorescence spectrometry (MFS), and circular dichroism (CD) spectroscopy. Higher stability and better reusability of lysozyme-HMBG than those of alternatives were also shown.This work describes the synthesis of three-dimensional (3D) hollow hierarchical mesoporous bioactive glass (HMBG) microspheres based on pine pollen. The HMBG microspheres perfectly copied the hierarchical porous structure of the natural pine pollen. This structural mimicry of the pollen grains resulted in a higher degree of adsorption of lysozyme on HMBG microspheres Hierarchically mesoporous bioactive glass (HMBG) was synthesized by using pine pollen template.HMBG has a complex, natural channel structure and pore size that matched the size of the lysozyme.The maximum adsorption capacity up to 648 ± 5.1 mg g−1. [ABSTRACT FROM AUTHOR]

The osteogenic and angiogenic responses of organisms to the ionic products of degradation of bioactive glasses (BGs) are being intensively investigated. The promotion of angiogenesis by copper (Cu) has been known for more than three decades. This element can be incorporated to delivery carriers, such as BGs, and the materials used in biological assays. In this work, Cu-containing mesoporous bioactive glass (MBG) in the SiO 2 -CaO-P 2 O 5 compositional system was prepared incorporating 5% mol Cu (MBG-5Cu) by replacement of the corresponding amount of Ca. The biological effects of the ionic products of MBG biodegradation were evaluated on a well-known endothelial cell line, the bovine aorta endothelial cells (BAEC), as well as in an in vivo zebrafish ( Danio rerio ) embryo assay. The results suggest that ionic products of both MBG (Cu free) and MBG-5Cu materials promote angiogenesis. In vitro cell cultures show that the ionic dissolution products of these materials are not toxic and promote BAEC viability and migration. In addition, the in vivo assay indicates that both exposition and microinjection of zebrafish embryos with Cu free MBG material increase vessel number and thickness of the subintestinal venous plexus (SIVP), whereas assays using MBG-5Cu enhance this effect. Statement of Significance Mesoporous bioactive glasses (MBGs) with high specific surface area, well-ordered pores, large pore volumes and controllable amount of ions are interesting to develop controlled drug delivery systems for bone tissue regeneration. Copper (Cu) incorporation to the basic SiO 2 -CaO-P 2 O 5 composition has attracted high interest due to its multifunctional biological properties. Promotion of angiogenesis is one of these properties, which can be integrated to the biomaterial with lower cost and higher stability when compared with growth factors. This work reports the synthesis and characterization of Cu-containing MBG evaluating its angiogenic properties in the subintestinal vessel zebrafish assay. This transgenic in vivo assay is merging as an alternative model providing short-time consuming protocols and facilities during pro-angiogenic drug screenings. The report shows that the ionic products of this MBG material delivered to the zebrafish incubation media significantly enhance angiogenesis in comparison with control groups. Besides, results indicate Cu ions may exhibit a synergic effect with Si, Ca, and P ions in angiogenesis stimulation both in vitro and in vivo . To our knowledge, this is the first time that zebrafish in vivo assays are used to evaluate angiogenic activity of ionic dissolution products from MBG materials. [ABSTRACT FROM AUTHOR]

Abstract: Mesoporous bioactive glass (MBG) of CaO–SiO2–P2O5 was synthesized using nonionic block copolymer (EO20PO70EO20, P123) and acetic anhydride as the template and catalyst, respectively. It was inferred that acetic anhydride could accelerate the hydrolysis of tetraethyl orthosilicate and the obtained by-product of acetic acid was harmless to the environment. The TEM analysis indicated that the synthesized MBG had two-dimensional (2D) hexagonal mesostructures, and the measured BET surface area, pore volume and pore diameter were 499m2/g, 0.70cm3/g and 6.1nm, respectively. Moreover, the synthesized MBG showed an excellent bioactivity in vitro as assessed by immersion studies in simulated body fluid (SBF). In a word, this work presents a simple and environment friendly route for synthesizing MBG by use of acetic anhydride as the catalyst and would find potential applications in tissue engineering and other fields. [Copyright &y& Elsevier]

• Silver acted as an intermediate ion and did not dissolve into silicate structure and then form AgNPs incorporated to glassy matrix. • Lower Ag in BG maintained higher percentage of Ag(1) and Ag clusters; higher Ag in BG increased the percentage of Ag(0) and the coalescence of AgNPs. • Bioactive glass with Ag compositions in the range of 1–10 mole ratio, presented the same antibacterial ability (MIC = 10 mg/mL) against anti-methicillin resistant Staphylococcus aureus (MRSA). In this study, we investigated the SiO 2 -CaO-P 2 O 5 mesoporous bioactive glass (MBG) system doped with Ag. The antibacterial capacity of the system was determined by loading and delivering silver nanoparticles (AgNPs) through the porous structure of MBG. According to X-ray diffraction (XRD) and solid-state magic angle spinning nuclear magnetic resonance (solid-state MAS-NMR) result, Ag-doped MBG maintained its parent glassy structure. Further, the solid-state MAS-NMR results indicated that the Ag content did not influence the network connectivity of the glass substrate. On the other hand, transmission electron microscopy (TEM) images indicated that AgNPs (size < 5 nm) were confined in mesoporous channels and homogeneously dispersed in the bioactive glass substrate. Coalescence of the AgNPs occurred with higher Ag content. The in vitro antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA) was the same for MBG with Ag compositions in the range of 1–10 mole ratio in bioactive glass (MIC=10 mg/mL). [ABSTRACT FROM AUTHOR]

Mesoporous bioactive glasses (MBGs) offer suitable platforms for drug/ion delivery in tissue engineering strategies. The main goal of this study was to prepare strontium (Sr)- and cobalt (Co)-doped MBGs; strontium is currently used in the treatment of osteoporosis, and cobalt is known to exhibit pro-angiogenic effects. Sr- and Co-doped mesoporous glasses were synthesized for the first time in a multicomponent silicate system via the sol–gel method by using P123 as a structure-directing agent. The glassy state of the Sr- and Co-doped materials was confirmed by XRD before immersion in SBF, while an apatite-like layer was detected onto the surface of samples post-immersion. The textural characteristics of MBGs were confirmed by nitrogen adsorption/desorption measurements. In vitro experiments including MTT assay, Alizarin red staining, and cell attachment and migration showed the cytocompatibility of all the samples as well as their positive effects on osteoblast-like cell line MG-63. Early experiments with human umbilical vein endothelial cells also suggested the potential of these MBGs in the context of angiogenesis. In conclusion, the prepared materials were bioactive, showed the ability to improve osteoblast cell function in vitro and could be considered as valuable delivery vehicles for therapeutics, like Co2+ and Sr2+ ions. [ABSTRACT FROM AUTHOR]