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Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo. RNA transcriptome sequencing demonstrated that BSG + 5%Fe3O4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe3O4 upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro. Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-β1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1β) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe3O4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

Borosilicate bioactive glasses exhibit excellent bioactivity and degradation properties; however, they suffer from the rapid release of bioactive elements at the initial stage of their degradation. Excessive local concentrations (such as those of B) can affect cell proliferation. Moreover, the degradation and mineralization ability of these glasses deteriorate at the later stages. Aiming to balance the release of bioactive elements during the whole process, herein, a borosilicate bioactive glass 18SiO2–6Na2O–8K2O–8MgO–22CaO–2P2O5–36B2O3 (mol%) was prepared using the melting method. Further, the effects of microcrystallization on the release of bioactive elements and in vitro degradation were studied. Results show that after heat treatment at temperatures over 620 °C, multiple microcrystalline phases, including Ca2SiO4, CaB2O4, and CaMgB2O5, form in the glass. The glass samples heat-treated within the range of 620–640 °C undergo appropriate devitrification degrees, decelerating the rate of pH increase of the immersion solution during the initial stage in comparison to those treated at lower temperatures. This results in a more continuous release of all bioactive elements and allows better control of the overall degradation. Contrarily, the more extensive devitrification degrees of glass samples heat-treated at higher temperatures reverse the pH increase and degradation trends. Since bone marrow mesenchymal stem cells and mouse embryonic osteoblast cells are pH-sensitive, inducing a suitable degree of devitrification proved to favor cell viability and enhance the mineralization capacity. Thus, different microcrystallization degrees provide new approaches for controlling the degradation and release of bioactive elements, resulting in the simultaneous enhancement of biosafety and bioactivity. [ABSTRACT FROM AUTHOR]

Derived Hench bioactive glass (BaG) containing boron (B) is explored in this work as it plays an important role in bone development and regeneration. B was also found to enhance BaG dissociation. However, it is only possible to incorporate a limited amount of B. To increase the amount of B in BaG, bioactive borosilicate glasses (BaG-Bx) were fabricated based on the use of the solution-gelation process (sol-gel). In this work, a high B content (20 wt.%) in BaG, respecting the conditions of bioactivity and biodegradability required by Hench, was achieved for the first time. The capability of BaG-Bx to form an apatite phase was assessed in vitro by immersion in simulated body fluid (SBF). Then, the chemical structure and the morphological changes in the fabricated BaG-Bx (x = 0, 5, 10 and 20) were studied. The formation of hydroxyapatite (HAp) layer was observed with X-ray diffraction (XRD) and infrared (IR) spectroscopy. The presence of HAp layer was confirmed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Enhanced bioactivity and chemical stability of BaG-Bx were evaluated with an ion exchange study based on Inductively Coupled Plasma–Optical Emission Spectrometry (ICP-OES) and energy dispersive spectroscopy (EDS). Results indicate that by increasing the concentration of B in BaG-Bx, the crystallization rate and the quality of the newly formed HAp layer on BaG-Bx surfaces can be improved. The presence of B also leads to enhanced degradation of BaGs in SBF. Accordingly, BAG-Bx can be used for bone regeneration, especially in children, because of its faster degradation as compared to B-free glass. [ABSTRACT FROM AUTHOR]

Borosilicate bioactive glasses exhibit excellent bioactivity and degradation properties; however, they suffer from the rapid release of bioactive elements at the initial stage of their degradation. Excessive local concentrations (such as those of B) can affect cell proliferation. Moreover, the degradation and mineralization ability of these glasses deteriorate at the later stages. Aiming to balance the release of bioactive elements during the whole process, herein, a borosilicate bioactive glass 18SiO2–6Na2O–8K2O–8MgO–22CaO–2P2O5–36B2O3 (mol%) was prepared using the melting method. Further, the effects of microcrystallization on the release of bioactive elements and in vitro degradation were studied. Results show that after heat treatment at temperatures over 620 °C, multiple microcrystalline phases, including Ca2SiO4, CaB2O4, and CaMgB2O5, form in the glass. The glass samples heat-treated within the range of 620–640 °C undergo appropriate devitrification degrees, decelerating the rate of pH increase of the immersion solution during the initial stage in comparison to those treated at lower temperatures. This results in a more continuous release of all bioactive elements and allows better control of the overall degradation. Contrarily, the more extensive devitrification degrees of glass samples heat-treated at higher temperatures reverse the pH increase and degradation trends. Since bone marrow mesenchymal stem cells and mouse embryonic osteoblast cells are pH-sensitive, inducing a suitable degree of devitrification proved to favor cell viability and enhance the mineralization capacity. Thus, different microcrystallization degrees provide new approaches for controlling the degradation and release of bioactive elements, resulting in the simultaneous enhancement of biosafety and bioactivity.

Controlled ion release and mineralization of bioactive glasses are essential to their applications in bone regeneration. Tuning the chemical composition and surface structure of glasses are the primary means of achieving this goal. However, most bioactive glasses exhibit a non-linear ion release behavior. Therefore, modifying the immersion environment of glasses through external stimuli becomes an approach. In this study, the ion release and mineralization properties of a borosilicate bioactive glass were investigated in the Tris buffer and K2HPO4 solutions with different pH. The glass had a faster ion release rate at a lower pH, but the overly acidic environment was detrimental to hydroxyapatite production. Using a direct current (DC) electric field as an external stimulus, the pH of the immersion solution could be modulated within a narrow range, thereby modulating ion release from the glass. As a result, significant increases in ion release were observed after three days, and the development of porous mineralization products on the glass surface after six days. This study demonstrates the effectiveness of the DC electric field in modulating the ion release of the bioactive glass in vitro and provides a potential way to regulate the degradation of the glass in vivo. [ABSTRACT FROM AUTHOR]

Derived Hench bioactive glass (BaG) containing boron (B) is explored in this work as it plays an important role in bone development and regeneration. B was also found to enhance BaG dissociation. However, it is only possible to incorporate a limited amount of B. To increase the amount of B in BaG, bioactive borosilicate glasses (BaG-Bx) were fabricated based on the use of the solution-gelation process (sol-gel). In this work, a high B content (20 wt.%) in BaG, respecting the conditions of bioactivity and biodegradability required by Hench, was achieved for the first time. The capability of BaG-Bx to form an apatite phase was assessed in vitro by immersion in simulated body fluid (SBF). Then, the chemical structure and the morphological changes in the fabricated BaG-Bx (x = 0, 5, 10 and 20) were studied. The formation of hydroxyapatite (HAp) layer was observed with X-ray diffraction (XRD) and infrared (IR) spectroscopy. The presence of HAp layer was confirmed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Enhanced bioactivity and chemical stability of BaG-Bx were evaluated with an ion exchange study based on Inductively Coupled Plasma–Optical Emission Spectrometry (ICP-OES) and energy dispersive spectroscopy (EDS). Results indicate that by increasing the concentration of B in BaG-Bx, the crystallization rate and the quality of the newly formed HAp layer on BaG-Bx surfaces can be improved. The presence of B also leads to enhanced degradation of BaGs in SBF. Accordingly, BAG-Bx can be used for bone regeneration, especially in children, because of its faster degradation as compared to B-free glass.

Implant-associated Staphylococcus aureus ( S. aureus ) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe 3 O 4 ) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo . RNA transcriptome sequencing demonstrated that BSG + 5%Fe 3 O 4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe 3 O 4 upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro . Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-β1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1β) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe 3 O 4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment., Competing Interests: Haobo Pan is an editorial board member for Biomedical Technology and was not involved in the editorial review or the decision to publish this article. All 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., (© 2024 The Authors.)

Controlled ion release and mineralization of bioactive glasses are essential to their applications in bone regeneration. Tuning the chemical composition and surface structure of glasses are the primary means of achieving this goal. However, most bioactive glasses exhibit a non-linear ion release behavior. Therefore, modifying the immersion environment of glasses through external stimuli becomes an approach. In this study, the ion release and mineralization properties of a borosilicate bioactive glass were investigated in the Tris buffer and K2HPO4 solutions with different pH. The glass had a faster ion release rate at a lower pH, but the overly acidic environment was detrimental to hydroxyapatite production. Using a direct current (DC) electric field as an external stimulus, the pH of the immersion solution could be modulated within a narrow range, thereby modulating ion release from the glass. As a result, significant increases in ion release were observed after three days, and the development of porous mineralization products on the glass surface after six days. This study demonstrates the effectiveness of the DC electric field in modulating the ion release of the bioactive glass in vitro and provides a potential way to regulate the degradation of the glass in vivo.

Chemical cross-linking was used to create nanocomposite hydrogels made up of gelatin (G) and borosilicate bioactive glass (BBG) with different content (0, 3, and 5 wt.%). The G/BBG nanocomposite hydrogels were studied for their morphology, mechanical properties, and viscoelasticity. SEM images revealed a macroporous interconnected structure with particles scattered across the pore walls. Studies of water absorption and degradation confirmed that the nanocomposite scaffolds were hydrophilic and biodegradable. The addition of 5% BBG to the scaffold formulations increased the compressive modulus by 413% and the compressive intensity by 20%, respectively. At all frequency ranges tested, the storage modulus (G′) was greater than the loss modulus (G″), revealing a self-standing elastic nanocomposite hydrogel. The nanocomposite scaffolds facilitated apatite formation while immersed in simulated body fluid (SBF). According to the findings, G/BBG nanocomposite scaffolds could be a promising biomaterial for bone regeneration.

Borosilicate bioactive glasses exhibit excellent bioactivity and degradation properties; however, they suffer from the rapid release of bioactive elements at the initial stage of their degradation. Excessive local concentrations (such as those of B) can affect cell proliferation. Moreover, the degradation and mineralization ability of these glasses deteriorate at the later stages. Aiming to balance the release of bioactive elements during the whole process, herein, a borosilicate bioactive glass 18SiO 2 -6Na 2 O-8K 2 O-8MgO-22CaO-2P 2 O 5 -36B 2 O 3 (mol%) was prepared using the melting method. Further, the effects of microcrystallization on the release of bioactive elements and in vitro degradation were studied. Results show that after heat treatment at temperatures over 620 °C, multiple microcrystalline phases, including Ca 2 SiO 4 , CaB 2 O 4 , and CaMgB 2 O 5 , form in the glass. The glass samples heat-treated within the range of 620-640 °C undergo appropriate devitrification degrees, decelerating the rate of pH increase of the immersion solution during the initial stage in comparison to those treated at lower temperatures. This results in a more continuous release of all bioactive elements and allows better control of the overall degradation. Contrarily, the more extensive devitrification degrees of glass samples heat-treated at higher temperatures reverse the pH increase and degradation trends. Since bone marrow mesenchymal stem cells and mouse embryonic osteoblast cells are pH-sensitive, inducing a suitable degree of devitrification proved to favor cell viability and enhance the mineralization capacity. Thus, different microcrystallization degrees provide new approaches for controlling the degradation and release of bioactive elements, resulting in the simultaneous enhancement of biosafety and bioactivity.

The development of synthetic scaffolds with a desirable combination of properties, such as bioactivity, the ability to locally deliver antibacterial agents and high osteogenic capacity, is a challenging but promising approach in bone tissue engineering. In this study, scaffolds of a borosilicate bioactive glass (composition: 6Na2O, 8K2O, 8MgO, 22CaO, 36B2O3, 18SiO2, 2P2O5; mol%) with controllable antibacterial activity were developed by doping the parent glass with varying amounts of Ag2O (0.05, 0.5, and 1.0 wt%). The addition of the Ag2O lowered the compressive strength and degradation of the bioactive glass scaffolds but it did not affect the formation of hydroxyapatite on the surface of the glass as determined by energy dispersive x-ray analysis, x-ray diffraction, and Fourier transform infrared analysis. The Ag2O-doped scaffolds showed a sustained release of Ag ions over more than 8 weeks in simulated body fluid and resistance against colonization by the bacterial strains Escherichia coli and Staphylococcus aureus. In vitro cell culture showed better adhesion, proliferation, and alkaline phosphatase activity of murine osteoblastic MC3T3-E1 cells on the Ag2O-doped bioactive glass scaffolds than on the undoped scaffolds. The results indicate that these Ag-doped borosilicate bioactive glass scaffolds may have potential in repairing bone coupled with providing a lower risk of bacterial infection. [ABSTRACT FROM AUTHOR]

The biomaterials with high osteogenic ability are being intensively investigated. In this study, we evaluated the bioactivity and osteogenesis of BG-Zn scaffolds in vitro and in vivo with a rodent calvarial defects model. Zinc containing borosilicate bioactive glass was prepared by doping glass with 1.5, 5 and 10 wt.% ZnO (denoted as BG-1.5Zn, BG-5Zn and BG-10Zn, respectively). When immersed in simulated body fluid, dopant ZnO retarded the degradation process, but did not affect the formation of hydroxyapatite (HA) after long-period soaking. BG-Zn scaffolds showed controlled release of Zn ions into the medium for over 8 weeks. Human bone marrow derived stem cells (hBMSCs) attached well on the BG-1.5Zn and BG-5Zn scaffolds, which exhibited no cytotoxicity to hBMSCs. In addition, the alkaline phosphatase activity of the hBMSCs increased with increasing dopant amount in the glass, while the BG-10Zn group showed over-dose of Zn. Furthermore, when implanted in rat calvarial defects for 8 weeks, the BG-5Zn scaffolds showed a significantly better capacity to regenerate bone tissue compared to the non-doping scaffolds. Generally, these results showed the BG-Zn scaffolds with high osteogenic capacity will be promising candidates using in bone tissue repair and regeneration. [ABSTRACT FROM AUTHOR]

Protein delivery and release from synthetic scaffold materials are major challenges within the field of bone tissue engineering. In this study, 13-93B1.5 borosilicate bioactive glass (BSG) base paste was 3D printed to produce BSG-based scaffolds with high porosity (59.85 ± 6.04%) and large pore sizes (350-400 μm) for functionalization with a sodium alginate (SA)/calcitonin gene-related peptide (CGRP) hydrogel mixture. SA/CGRP hydrogel was uniformly filled into the interconnected pores of 3D printed BSG constructs to produce BSG-SA/CGRP scaffolds which were subject to bioactivity and biocompatibility analysis. BSG scaffolds filled with SA hydrogel underwent dissolution in simulated body fluid (SBF), resulting in the precipitation of hydroxyapatite (HA) on the borosilicate glass evidenced by scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Around 90% of CGRP was released from scaffolds after 7 days of immersion in SBF, reaching a final released concentration of 893.00 ± 63.30 ng/mL. Cellular adhesion, proliferation, and differentiation of human bone marrow mesenchymal stem cells (HBMSCs) cultured with BSG-SA/CGRP scaffolds revealed improved biocompatibility and osteogenic capabilities compared with BSG-SA scaffolds in the absence of CGRP. When subcutaneously implanted in rat models, BSG-SA/CGRP scaffolds induced low localized inflammation without causing bodily harm in vivo. Findings revealed that bioactive glass scaffolds incorporating CGRP met the scaffold requirements for bone regeneration and that the addition of CGRP promoted osteogenic differentiation where it may potentially be utilized for future regenerative applications., (Copyright © 2022. Published by Elsevier B.V.)

Chemical cross-linking was used to create nanocomposite hydrogels made up of gelatin (G) and borosilicate bioactive glass (BBG) with different content (0, 3, and 5 wt.%). The G/BBG nanocomposite hydrogels were studied for their morphology, mechanical properties, and viscoelasticity. SEM images revealed a macroporous interconnected structure with particles scattered across the pore walls. Studies of water absorption and degradation confirmed that the nanocomposite scaffolds were hydrophilic and biodegradable. The addition of 5% BBG to the scaffold formulations increased the compressive modulus by 413% and the compressive intensity by 20%, respectively. At all frequency ranges tested, the storage modulus (G′) was greater than the loss modulus (G″), revealing a self-standing elastic nanocomposite hydrogel. The nanocomposite scaffolds facilitated apatite formation while immersed in simulated body fluid (SBF). According to the findings, G/BBG nanocomposite scaffolds could be a promising biomaterial for bone regeneration. [ABSTRACT FROM AUTHOR]

• WH contained BBG bone cements with different BBG/WH ratio were prepared. • The addition of WH significantly improved the cohesiveness of bone cement. • WH contained BBG bone cements have good mineralization ability. • The addition of WH improved the cell adhesion, proliferation and ALP activity. Since borosilicate bioactive glass (BBG) is famous for its degradation, biocompatibility and osteogenesis, and the whitlockite (WH: Ca 18 Mg 2 (HPO 4) 2 (PO 4) 12) is one of the main components of inorganic phase of bone which plays an important role in bone growth, herein, we have firstly designed a novel bone cement by incorporating WH with BBG (BBG/WH). Results indicated that the addition of WH had significantly enhanced the cohesiveness of bone cement. Furthermore, the mechanism of the incorporation of WH in BBG had also been investigated that the cross link, Van der Waals force and WH/sodium alginate interaction has worked in the BBG/WH. Additionally, the BBG/WH bone cement exhibited excellent mineralization ability in vitro with continuously released Ca2+ and Mg2+ when immersed in simulated body fluid (SBF). Particularly, BBG4:WH2 bone cement had the best cell proliferation and osteogenic differentiation performance compared with other groups when cultured with rat bone marrow mesenchymal stem cells (rBMSCs). [ABSTRACT FROM AUTHOR]

Background: In the field of bone tissue engineering, there has been an increasing interest in biomedical materials with both high angiogenic ability and osteogenic ability. Among various osteogenesis materials, bioactive borosilicate and borate glass scaffolds possess suitable degradation rate and mechanical strength, thus drawing many scholars' interests and attention., Objective: In this study, we fabricated bioactive glass scaffolds composed of borosilicate 2B6Sr using the Template-Method and incorporated Dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug possessing good angiogenic ability, to improve bone regeneration., Methods: The in-vitro studies showed that porous borosilicate bioactive glass scaffolds released slowly, a steady amount of DMOG and stimulated the proliferation and osteogenic differentiation of human bone marrow stromal cells hBMSCs., Results: In-vivo studies showed that the borosilicate bioactive glass scaffolds could significantly promote new bone formation and neovascularization in rats' calvarial bone defects., Conclusion: These results indicated that DMOG-incorporated bioactive glass scaffold is a successful compound with excellent angiogenesis-osteogenesis ability, which has favorable clinical prospects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In the field of tissue engineering, there is currently increasing interest in new biomedical materials with high osteogenic ability and comparable mechanical function to repair bone defects. Three-dimensional (3-D) bioactive borosilicate glass (BG) scaffolds exhibit uniform interconnected macro-pores, high porosity and high compressive strength. In this study, we fabricated 3-D BG scaffolds by the 3D printing technique, then coated the surface of the 3-D BG scaffolds with mesoporous bioactive glass (MBG) (BG-MBG scaffold). Methods: The biocompatibility of the BG-MBG scaffolds was evaluated by assessing biodegradability, cell proliferation, alkaline phosphatase (ALP) activity and by quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of osteogenic gene expression with human bone marrow stromal cells (hBMSCs). Moreover, the BG-MBG scaffolds were used to repair rat femoral defects and their performance was evaluated using microcomputed tomography (micro-CT), fluorescence labeling, histological analysis and immunohistochemical (IHC) analysis. Results: The results showed that the BG-MBG scaffolds possessed ordered nearly 4nm meso-pores and regular macro-pores, as well as good biodegradability, and that they stimulated the proliferation and osteogenic differentiation of hBMSCs. In in vivo studies, the result of micro-CT reconstructed images (BG-9M group, 0.63 ± 0.02 g/cm 3 and BG group 0.13 ± 0.02 g/cm 3 ) and van Gieson staining (BG-9M groups, 62.67 ± 3.39% and BG group, 12.33 ± 2.58%) showed that the BG-MBG scaffolds could significantly enhance new bone formation in both inner and peripheral scaffolds in defects, in and in without the presence of growth factors or stem cells ( P < 0.05). Conclusions: It is believed from these results that the BG-MBG scaffolds possess excellent osteoinductive and osteogenic properties which will make them appealing candidates for bone defect repair. The novelty of our research is to provide a new material to treat bone defects in clinic., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.