Osteogenic and angiogenic potential of molybdenum-containing mesoporous bioactive glass nanoparticles: An ionic approach to bone tissue engineering.

Biomaterials intended for application in bone tissue engineering (BTE) ideally stimulate osteogenesis and angiogenesis simultaneously, as both mechanisms are of critical importance for successful bone regeneration. Mesoporous bioactive glass nanoparticles (MBGNs) can be tailored towards specific biological needs, for example by addition of ions like Molybdenum (Mo). While Mo has been shown to enhance osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (BMSCs) as well as their ability to form and mature a primitive osseous extracellular matrix (ECM), there are contradictory findings regarding its impact on angiogenesis. In this study, the effects of Mo-MBGNs (mol%: 70 SiO2, 25 CaO, 5 MoO3) on viability, proliferation, osteogenic differentiation, ECM formation and angiogenic response of BMSCs were compared to undoped MBGNs (in mol%: 70 SiO2, 30 CaO) and a control group of BMSCs. Furthermore, a human umbilical vein endothelial cells tube formation assay and a chorioallantoic membrane-assay using fertilized chicken eggs were used to analyze angiogenic properties. Mo-MBGNs were cytocompatible and promoted the proliferation of BMSCs. Furthermore, Mo-MBGNs showed promising osteogenic properties as they enhanced osteogenic differentiation, ECM formation and maturation as well as the gene expression and protein production of relevant osteogenic factors in BMSCs. However, despite the promising outcome on osteogenic properties, the addition of Mo to MBGNs resulted in anti-angiogenic effects. Due to the high relevance of vascularization in-vivo, the anti-angiogenic properties of Mo-MBGNs might hamper their osteogenic properties and therefore might restrict their performance in BTE applications. These limitations can be overcome by the addition of ions with distinct pro-angiogenic properties to the Mo-MBGNs-composition. Due to their promising osteogenic properties, Mo-MBGNs constitute a suitable basis for further research in the field of ionic (growth factor free) BTE.

Quantitative study of early-stage transient bacterial adhesion to bioactive glass and glass ceramics: atomic force microscopic observations.

Antimicrobial potential of bioactive glass (BAG) makes it promising for implant applications, specifically overcoming the toxicity concerns associated with traditional antibacterial nanoparticles. The 58S composition of BAG (with high Ca and absence of Na) has been known to exhibit excellent bioactivity and antibacterial behaviour, but the mechanisms behind have not been investigated in detail. In this pioneering study, we are using Atomic Force Microscopy (AFM) to gain insights into 58S BAG's adhesive interactions with planktonic cells of both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria; along with the impact of crystallinity on antibacterial properties. We have recorded greater bacterial inhibition by amorphous BAG compared to semi-crystalline glass-ceramics and stronger effect against gram-negative bacteria via conventional long-term antibacterial tests. AFM force distance curves has illustrated substantial bonding between bacteria and BAG within the initial one second (observed at a gap of 250 ms) of contact, with multiple binding events. Further, stronger adhesion of BAG with E.coli (~ 6 nN) compared to S. aureus (~ 3 nN) has been found which can be attributed to more adhesive nano-domains (size effect) distributed uniformly on E.coli surface. This study has revealed direct evidence of impact of contact time and 58S BAG's crystalline phase on bacterial adhesion and antimicrobial behaviour. Current study has successfully demonstrated the mode and mechanisms of initial bacterial adhesion with 58S BAG. The outcome can pave the way towards improving the designing of implant surfaces for a range of biomedical applications.

Osteogenic potency of dental stem cell-composite scaffolds in an animal cleft palate model.

Objective: To evaluate the osteogenic potency of stem cells isolated from human exfoliated deciduous teeth (SHED) in polycaprolactone with gelatin surface modification (PCL-GE) and poly (lactic-co-glycolic acid)-bioactive glass composite (PLGA-bioactive glass (BG)) scaffolds after implantation in a rat cleft model. Methods: Cleft palate-like lesions were induced in Sprague-Dawley rats by extracting the right maxillary first molars and drilling the intact alveolar bone. Rats were then divided into five groups: Control, PCL-GE, PCL-GE-SHED, PLGA-BG, and PLGA-BG-SHED, and received corresponding composite scaffolds with/without SHED at the extraction site. Tissue samples were collected at 2, 3, and 6 months post-implantation (4 rats per group). Gross and histological analyses were conducted to assess osteoid or bone formation. Immunohistochemistry for osteocalcin and human mitochondria was performed to evaluate bone components and human stem cell viability in the tissue. Results: Bone tissue formation was observed in the PCL-GE and PLGA-BG groups compared to the control, where no bone formation occurred. PLGA-BG scaffolds demonstrated greater bone regeneration potential than PCL-GE over 2-6 months. Additionally, scaffolds with SHED accelerated bone formation compared to scaffolds alone. Osteocalcin expression was detected in all rats, and positive immunoreactivity for human mitochondria was observed in the regenerated bone tissue with PCL-GE-SHED and PLGA-BG-SHED. Conclusion: PCL-GE and PLGA-BG composite scaffolds effectively repaired and regenerated bone tissue in rat cleft palate defects. Moreover, scaffolds supplemented with SHED exhibited enhanced osteogenic potency. Clinical significance: PCL-GE and PLGA-BG scaffolds, augmented with SHED, emerge as promising biomaterial candidates for addressing cleft repair and advancing bone tissue engineering endeavors.

Multifunctional gallium doped bioactive glasses: a targeted delivery for antineoplastic agents and tissue repair against osteosarcoma.

Osteosarcoma is the mostly commonly occurring primary bone cancer. Despite comprehensive treatment programs including neoadjuvant chemotherapy and tumour resection, survival rates have not improved significantly since the 1970s. Survival rates are dramatically reduced for patients who suffer a local recurrence. Furthermore, primary bone cancer patients are at increased risk of bone fractures. Consequently, there is an urgent need for alternative treatment options. In this paper we report the development of novel gallium doped bioactive glass that selectively kill bone cancer cells whilst simultaneously stimulating new bone growth. Here we show, using a combination of MTT, LIVE/DEAD assays and image analysis, that bioactive glasses containing gallium oxide are highly toxic and reduce both the proliferation and migration of bone cancer cells (Saos-2) in a dose dependant manner. Glasses containing 5 mol% gallium oxide reduced the viability of osteosarcoma cells by 99% without being cytotoxic to the non-cancerous normal human osteoblasts (NHOst) control cells. Furthermore, FTIR and Energy-dispersive X-ray spectroscopy results confirmed the formation of an amorphous calcium phosphate / hydroxy apatite layer on the surface of the bioactive glass particulates, after 7 days incubating in simulated body fluid, indicating the early stages of bone formation. These materials show significant potential for use in bone cancer applications as part of a multimodal treatment. .

Multifunctional Bionic Periosteum with Ion Sustained-Release for Bone Regeneration.

In this study, a novel bionic periosteum (BP)-bioactive glass fiber membrane (BGFM) is designed. The introduction of magnesium ion (Mg2+) and zinc ion (Zn2+) change the phase separation during the electrospinning (ES) jet stretching process. The fiber's pore structure transitions from connected to closed pores, resulting in a decrease in the rapid release of metal ions while also improving degradation via reducing filling quality. Additionally, the introduction of magnesium (Mg) and zinc (Zn) lead to the formation of negative charged tetrahedral units (MgO4 2- and ZnO4 2-) in the glass network. These units effectively trap positive charged metal ions, further inhibiting ion release. In vitro experiments reveal that the deigned bionic periosteum regulates the polarization of macrophages toward M2 type, thereby establishing a conducive immune environment for osteogenic differentiation. Bioinformatics analysis indicate that BP enhanced bone repair via the JAK-STAT signaling pathway. The slow release of metal ions from the bionic periosteum can directly enhance osteogenic differentiation and vascularization, thereby accelerating bone regeneration. Finally, the bionic periosteum exhibits remarkable capabilities in angiogenesis and osteogenesis, demonstrating its potential for bone repair in a rat calvarial defect model.

Tailored Bioactive Glass Coating: Navigating Devitrification Toward a Superior Implant Performance.

The development of well-adherent, amorphous, and bioactive glass coatings for metallic implants remains a critical challenge in biomedical engineering. Traditional bioactive glasses are susceptible to crystallization and exhibit a thermal expansion mismatch with implant materials. This study introduces a novel approach to overcome these limitations by employing systematic Na2O substitution with CaO in borosilicate glasses. In-depth structural analysis (MD simulations, Raman spectroscopy, and NMR) reveals a denser network with smaller silicate rings, enhancing thermal stability, reducing thermal expansion, and influencing dissolution kinetics. This tailored composition exhibited optimal bioactivity (in vitro formation of bone-like apatite within 3 days) and a coefficient of thermal expansion closely matching Ti-6Al-4V, a widely used implant material. Furthermore, a consolidation process, meticulously designed with insights from crystallization kinetics and the viscosity-temperature relationship, yielded a crack-free, amorphous coating on Ti-6Al-4V substrates. This novel coating demonstrates excellent cytocompatibility and strong antibacterial action, suggesting superior clinical potential compared with existing technologies.

Multifunctional Sr,Mg-Doped Mesoporous Bioactive Glass Nanoparticles for Simultaneous Bone Regeneration and Drug Delivery.

Mesoporous bioactive glass nanoparticles (MBGNs) doped with therapeutical ions present multifunctional systems that enable a synergistic outcome through the dual delivery of drugs and ions. The aim of this study was to evaluate influence of co-doping with strontium and magnesium ions (SrMg-MBGNs) on the properties of MBGNs. A modified microemulsion-assisted sol-gel synthesis was used to obtain particles, and their physicochemical properties, bioactivity, and drug-loading/release ability were evaluated. Indirect biological assays using 2D and 3D cell culture models on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and endothelial EA.hy926 cells, respectively, were used to determine biocompatibility of MBGNs, their influence on alkaline phosphatase (ALP) production, calcium deposition, and cytoskeletal organization. Results showed that Sr,Mg-doping increased pore volume and solubility, and changed the mesoporous structure from worm-like to radial-dendritic, which led to a slightly accelerated drug release compared to pristine MBGNs. Biological assays confirmed that particles are biocompatible, and have ability to slightly induce ALP production and calcium deposition of hBM-MSCs, as well as to significantly improve the proliferation of EA.hy926 compared to biochemical stimulation via vascular endothelial growth factor (VEGF) administration or regular media. Fluorescence staining revealed that SrMg-MBGNs had a similar effect on EA.hy926 cytoskeletal organization to the VEGF group. In conclusion, Sr,Mg-MBGNs might be considered promising biomaterial for biomedical applications.

Borate bioactive glass enhances 3D bioprinting precision and biocompatibility on a sodium alginate platform via Ca2+ controlled self-solidification.

Sodium alginate (SA) has gained widespread acclaim as a carrier medium for three-dimensional (3D) bioprinting of cells and a diverse array of bioactive substances, attributed to its remarkable biocompatibility and affordability. The conventional approach for fabricating alginate-based tissue engineering constructs entails a post-treatment phase employing a calcium ion solution. However, this method proves ineffectual in addressing the predicament of low precision during the 3D printing procedure and is unable to prevent issues such as non-uniform alginate gelation and substantial distortions. In this study, we introduced borate bioactive glass (BBG) into the SA matrix, capitalizing on the calcium ions released from the degradation of BBG to incite the cross-linking reaction within SA, resulting in the formation of BBG-SA hydrogels. Building upon this fundamental concept, it unveiled that BBG-SA hydrogels greatly enhance the precision of SA in extrusion-based 3D printing and significantly reduce volumetric contraction shrinkage post-printing, while also displaying certain adhesive properties and electrical conductivity. Furthermore, in vitro cellular experiments have unequivocally established the excellent biocompatibility of BBG-SA hydrogel and its capacity to actively stimulate osteogenic differentiation. Consequently, BBG-SA hydrogel emerges as a promising platform for 3D bioprinting, laying the foundation for the development of flexible, biocompatible electronic devices.

Exploratory Investigation of Zinc-Modified Borosilicate Bioactive Glass: A New Methodology for Its Biocompatibility, Immunoregulation, and Pro-Angiogenic Property Evaluation.

The assessment of biodegradable materials, such as bioactive glass, under the existing ISO 10993 standard test methods poses a significant challenge due to potential cell viability impairment caused by the accumulation of degraded products in a static environment. Therefore, innovative methodologies are urgently needed to tailor the unique biodegradation characteristics of these materials, providing more precise and scientific insights into biosafety and efficacy verification. Motivation by its bidirectional regulation of angiogenesis and immunity, zinc (Zn) was incorporated into sol-gel-derived borosilicate bioactive glasses (SBSGs) to fabricate Zn-incorporated borosilicate bioactive glasses (SBSG-Zn) to complement the tissue repair capabilities of bioactive glasses. Both SBSG and SBSG-Zn glasses consist of nanosized particles, slit mesoporous pores, high specific surface areas, and bioreactivity. In vitro comparative analysis, conducted according to ISO 10993 standards, demonstrates that only at suitable dilution rates─such as the 8-fold dilution employed in this study─do extracts of SBSG and SBSG-Zn glasses exhibit low cytotoxicity when cultured with human umbilical vein endothelial cells (HUVECs). Notably, SBSG-Zn glasses show optimal promotion of angiogenic gene expression in HUVECs. Furthermore, within an appropriate concentration range of released ions, SBSG-Zn glass extracts not only promote cell survival but also modulate the expression of anti-inflammatory genes while simultaneously inhibiting pro-inflammatory genes concurrently. After being implanted in rat subcutaneous defect models, both SBSG and SBSG-Zn glasses demonstrated the local immunoregulation and angiogenic effects. SBSG-Zn stands out by demonstrating superior modulation of M1/M2 polarization in macrophages as validated by altered secretion of key factors in macrophages and expression of relevant growth factors in HUVECs. These findings underscore the potential for convenient manipulation of localized angiogenic and immunoregulation through the incorporation of zinc into bioactive glass, emphasizing the importance of ensuring the appropriate ion doses are applied for achieving optimal therapeutic efficiency.

A Comparative Evaluation of the Remineralization Potential of Two Contemporary Bioactive Glass-containing Dentifrices on Artificially Demineralized Human Enamel: An In Vitro Study.

Background: There is limited literature comparing the remineralization potential of these two dentifrices, Elsenz™, which contains fluoro calcium (Ca) phosphosilicate, and Shy-NM™, which contains Ca sodium phosphosilicate, are a few of the remineralizing agents. Aim: To assess and compare the remineralization potential of Elsenz™ and Shy-NM™ dentifrices on artificially induced carious lesions on permanent teeth, using the Vickers microhardness measuring method and scanning electron microscope (SEM) connected to energy dispersive X-ray analysis after laboratory stimulation of the oral environment employing the pH cycling model. Materials and methods: A total of 30 sound human premolar teeth were divided into six groups for both parameters. Group I-Elsenz™ dentifrice, group II-Shy-NM™ dentifrice, and group III-control. The surface microhardness (SMH) of the test specimens was evaluated followed by a scanning electron microscope with energy dispersive analysis (SEM-EDAX). The specimens were tested at baseline, demineralization, and remineralization. The collected data were subjected to statistical analysis. Results: Surface microhardness following remineralization with Elsenz™ was 359 Vickers hardness number (VHN), and with Shy-NM™ was 312 VHN. Elsenz™ showed significantly higher remineralization compared to Shy-NM™ (p = 0.002). The SEM-EDAX of the tooth specimens after remineralization revealed an increase in the Ca weight percentage (wt%) compared with demineralization values, which was statistically significant for both Elsenz™ (45.95 ± 3.55%) and Shy-NM™ (47.24 ± 1.99%), along with an increase in the phosphorus wt%, which was statistically significant for Elsenz™ (20.25 ± 0.95%) compared to Shy-NM™ (19.95 ± 0.59%). Conclusion: Within the scope of this study, the incorporation of fluoride in bioactive glass (BAG) in Elsenz™ had the potential to remineralize enamel better than Shy-NM™ dentifrice. It can, therefore, be concluded that Elsenz™, when compared with Shy-NM™, would be effective in inhibiting demineralization. How to cite this article: Thoutam SV, Kumar S, Naidu J. A Comparative Evaluation of the Remineralization Potential of Two Contemporary Bioactive Glass-containing Dentifrices on Artificially Demineralized Human Enamel: An In Vitro Study. Int J Clin Pediatr Dent 2024;17(4):451-455.

Sol-gel-derived calcium silicate cement incorporating collagen and mesoporous bioglass nanoparticles for dental pulp therapy.

OBJECTIVE: Calcium silicate cements (CSCs) are often used in endodontics despite some limitations related to their physical properties and antibacterial efficacy. This study aimed to develop and demonstrate the viability of a series of CSCs that were produced by sol-gel method and further modified with mesoporous bioactive glass nanoparticles (MBGNs) and collagen, for endodontic therapy. METHODS: Calcium silicate (CS) particles and MBGNs were synthesized by the sol-gel method, and their elemental, molecular, and physical microstructure was characterized. Three CSCs were developed by mixing the CS with distilled water (CS+H2O), 10 mg/mL collagen solution (CS+colH2O), and MBGNs (10 %) (CSmbgn+colH2O). The mixing (MT) and setting (ST) times of the CSCs were determined, while the setting reaction was monitored in real-time. Antibacterial efficacy against Enterococcus faecalis (E. faecalis) and regenerative potential on dental pulp stem cells (DPSCs) were also analyzed. RESULTS: The CS+H2O displayed a ST comparable to commercial products, while CSmbgn+colH2O achieved the longest MT of 68 s and the shortest ST of 8 min. All the experimental CSCs inhibited the growth of E. faecalis. Additionally, compared to the control group, CSCs supported cell proliferation and spreading and mineralized matrix production, regardless of their composition. SIGNIFICANCE: Tested CSCs presented potential as candidates for pulp therapy procedures. Future research should investigate the pulp regeneration mechanisms alongside rigorous antibacterial evaluations, preferably with multi-organism biofilms, executed over extended periods.

Three-dimensional porous polycaprolactone/chitosan/bioactive glass scaffold for bone tissue engineering.

Three-dimensional (3D) porous scaffolds based on polycaprolactone (PCL)/chitosan (CS)/bioactive glass (BG) nanoparticle composites were fabricated by the freeze-drying technique for bone tissue engineering. The physiochemical properties of the developed PCL/CS/BG scaffolds were studied using FTIR, XRD, EDX and SEM. Furthermore, the swelling degree, porosity, water retention ability, compression strength, in vitro biodegradation, bioactivity and biocompatibility of the scaffolds were examined. The PCL/CS/BG scaffolds with 4 wt. % of BG content presented adequate pore size (106 µm), porosity (156%), water swelling degree (128%), water retention ability (179%), compressive strength (3.7 MPa) and controlled degradation behavior, which could be ideal for bone tissue engineering. The PCL/CS/BG composite scaffolds showed good antimicrobial activity against both test bacteria and fungi. The MTT assay demonstrated the biocompatibility of PCL/CS/BG scaffolds against C3H10T1/2 cell line. The Alizarin red staining assay confirmed the osteogenic activity of the PCL/CS/BG scaffolds.

Sustainable heavy metal (Cr(VI) ion) remediation: Ternary blend approach with chitosan, carboxymethyl cellulose, and bioactive glass.

Heavy metal pollution poses a significant environmental challenge to worldwide, especially in developing countries. This study focuses on eliminating the heavy metal chromium (VI) ion from wastewater, employing an eco-friendly and economical ternary blend composed of Chitosan (CS), Carboxymethyl cellulose (CMC), and bioactive glass (BAG). The innovative bioactive glass is crafted from biosilica extracted from biowaste of cow dung ash, calcium oxide from eggshell ash, and phosphorus pentoxide. The CS/CMC/BAG blend is prepared via sol-gel method and characterized using XRD, FT-IR, TGA, BET, TEM and SEM revealing a porous structural morphology during blending. Batch adsorption studies explore various parameters such as pH, adsorbent dose, contact time and initial metal ion concentrations. The results are then evaluated through adsorption kinetics and adsorption isotherms (Langmuir, Freundlich, D-R, and Temkin isotherm modeling). The investigation concludes that the optimal conditions for Cr (VI) removal are pH 3, contact time of 300 min, adsorbent dosage of 0.5 g, and an initial metal ion concentration of 50 ppm. The adsorption isotherm model indicates an excellent fit with the Freundlich isotherm (R2 = 0.9576) and pseudo-second-order kinetics (R2 = 0.981). In summary, the CS/CMC/BAG ternary blend exhibits a remarkable ability to effectively remove heavy metal Cr(VI) ions from industrial wastewater.

The combination of arginine and fluoride-containing bioactive glass acted synergistically in inhibiting enamel demineralization in permanent teeth.

OBJECTIVES: To evaluate the in-vitro efficacy of inhibiting enamel demineralization using arginine in combination with fluoride-containing bioactive glass (FBG). METHODS: In this study, the healthy enamel blocks were first demineralized in acetic acid for 24 h, then soaked in anti-demineralization treatment solutions containing either arginine or FBG or both for 96 h.The specimens treated in acetic acid were applied as the control group. The pH, calcium and phosphorus ion concentrations of the solutions were measured before and after treatment. Changes in enamel mineral weight, microhardness, and composition were also analyzed. RESULTS: The present of arginine facilitated fluorine release from treatment solutions with the presence of FBG. Both arginine and FBG significantly increased the pH of treatment solutions and prevented the further mineral weight loss compared to the control group. All anti-demineralization treatment groups showed significant increases in microhardness, but there was no statistical difference among the treatment groups. The SEM analysis showed enamel restoration in the arginine and FBG groups upon treatment, while the combined groups showing a superior anti-demineralization efficacy. 19F NMR showed the formation of fluorapatite in samples treated with solutions containing FBG. CONCLUSIONS: Both arginine and FBG could inhibit enamel demineralization to some extent, and their combination demonstrated an enhanced anti-demineralization efficacy. The low-concentration combination group exhibited anti-demineralization effects comparable to those of high-concentration ones. CLINICAL SIGNIFICANCE: This study introduces a new approach for caries prevention by combining the application of arginine and FBG. The release of fluorine promoted by the presented arginine along with calcium and phosphorus ions from FBG facilitated FAP formation. Additionally, the increment of pH resulting from arginine and FBG degradation further prevents enamel demineralization.

Fabrication of Electrospun Double Layered Biomimetic Collagen-Chitosan Polymeric Membranes with Zinc-Doped Mesoporous Bioactive Glass Additives.

Several therapeutic approaches have been developed to promote bone regeneration, including guided bone regeneration (GBR), where barrier membranes play a crucial role in segregating soft tissue and facilitating bone growth. This study emphasizes the importance of considering specific tissue requirements in the design of materials for tissue regeneration, with a focus on the development of a double-layered membrane to mimic both soft and hard tissues within the context of GBR. The hard tissue-facing layer comprises collagen and zinc-doped bioactive glass to support bone tissue regeneration, while the soft tissue-facing layer combines collagen and chitosan. The electrospinning technique was employed to achieve the production of nanofibers resembling extracellular matrix fibers. The production of nano-sized (~116 nm) bioactive glasses was achieved by microemulsion assisted sol-gel method. The bioactive glass-containing layers developed hydroxyapatite on their surfaces starting from the first week of simulated body fluid (SBF) immersion, demonstrating that the membranes possessed favorable bioactivity properties. Moreover, all membranes exhibited distinct degradation behaviors in various mediums. However, weight loss exceeding 50% was observed in all tested samples after four weeks in both SBF and phosphate-buffered saline (PBS). The double-layered membranes were also subjected to mechanical testing, revealing a tensile strength of approximately 4 MPa. The double-layered membranes containing zinc-doped bioactive glass demonstrated cell viability of over 70% across all tested concentrations (0.2, 0.1, and 0.02 g/mL), confirming the excellent biocompatibility of the membranes. The fabricated polymer bioactive glass composite double-layered membranes are strong candidates with the potential to be utilized in tissue engineering applications.

Development of PHBV electrospun fibers containing a borate bioactive glass doped with Co, Cu, and Zn for wound dressings.

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers embedded with borate glasses of 45B5 composition doped with Co2+, Cu2+, and Zn2 +(46.1 B2O326.9-X CaO24.4 Na2O2.6 P2O5, X CoO/CuO/ZnO mol % (X = 0-5)) were produced by electrospinning for wound healing applications. Prior to their addition, the glasses exhibited two broad halos typical of a vitreous borate network, which were mainly composed of ring-type metaborate structural units. The particle distribution in the PHBV nanofibers embedded with 45B5 borate bioactive glasses is present in isolated and agglomerated states, being partially coated by a polymeric layer-except for the cobalt-doped glass, which resulted in a successful encapsulation with 100% embedding efficiency. The incorporation of the glasses reduced the PHBV crystallinity degree and its decomposition temperature, as well as its mechanical properties, including Young's modulus, tensile strength, and elongation at break. The neat PHBV fibers and those containing the cobalt-doped glasses demonstrated great cytocompatibility with human keratinocytes (HaCat), as suggested by the high cell viability after 7 days of exposure. Further studies are needed to fully understand the wound healing potential of these fibers, but our results significantly contribute to the area.

Rod-Shaped Mesoporous Zinc-Containing Bioactive Glass Nanoparticles: Structural, Physico-Chemical, Antioxidant, and Immuno-Regulation Properties.

Bioactive glass nanoparticles (BGNs) are applied widely in tissue regeneration. Varied micro/nanostructures and components of BGNs have been designed for different applications. In the present study, nanorod-shaped mesoporous zinc-containing bioactive glass nanoparticles (ZnRBGNs) were designed and developed to form the bioactive content of composite materials for hard/soft tissue repair and regeneration. The nanostructure and components of the ZnRBGNs were characterized, as were their cytocompatibility and radical-scavenging activity in the presence/absence of cells and their ability to modulate macrophage polarization. The ZnRBGNs possessed a uniform rod shape (length ≈ 500 nm; width ≈ 150 nm) with a mesoporous structure (diameter ≈ 2.4 nm). The leaching liquid of the nanorods at a concentration below 0.5 mg/mL resulted in no cytotoxicity. More significant improvements in the antioxidant and M1-polarization-inhibiting effects and the promotion of M2 polarization were found when culturing the cells with the ZnRBGNs compared to when culturing them with the RBGNs. The doping of the Zn element in RBGNs may lead to improved antioxidant and anti-inflammatory effects, which may be beneficial in tissue regeneration/repair.

Nano-vibration exciter: Hypoxia-inducible factor 1 signaling pathway-mediated extracellular vesicles as bioactive glass substitutes for bone regeneration.

Bioactive glasses (BG) play a vital role in angiogenesis and osteogenesis through releasing functional ions. However, the rapid ion release in the early stage will cause excessive accumulation of metal ions, which in turn leads to obvious cytotoxicity, long-term inflammation, and bone repair failure. Inspired by the vibration exciter, small extracellular vesicles (sEVs) obtained by treating mesenchymal stem cells with copper-doped bioactive glass (CuBG-sEVs), is prepared as a nano-vibration exciter. The nano-vibration exciter can convert the ion signals of CuBG into biochemical factor signals through hypoxia-inducible factor 1 (HIF-1) signaling pathway and its activated autophagy, so as to better exert the osteogenic activity of BG. The results showed that CuBG extracts could significantly improve the enrichment of key miRNAs and increase the yield of CuBG-sEVs by activating HIF-1 signaling pathway and its activated autophagy. Cell experiments showed that CuBG-sEVs are favor to cell recruitment, vascularization and osteogenesis as the enrichment of key miRNAs. The animal experiments results showed that CuBG-sEVs stimulated angiogenesis mediated by CD31 and promoted bone regeneration by activating signaling pathways related to osteogenesis. These findings underscored the significant potential of sEVs as alternative strategies to better roles of BG.

Alginate-Sr/Mg Containing Bioactive Glass Scaffolds: The Characterization of a New 3D Composite for Bone Tissue Engineering.

In bone regeneration, combining natural polymer-based scaffolds with Bioactive Glasses (BGs) is an attractive strategy to improve the mechanical properties of the structure, as well as its bioactivity and regenerative potential. Methods: For this purpose, a well-studied alginate/hydroxyapatite (Alg/HAp) porous scaffold was enhanced with an experimental bioglass (BGMS10), characterized by a high crystallization temperature and containing therapeutic ions such as strontium and magnesium. This resulted in an improved biological response compared to 45S5 Bioglass®, the "gold" standard among BGs. Porous composite scaffolds were fabricated by freeze-drying technique and characterized by scanning electron microscopy and microanalysis, infrared spectroscopy, and microcomputed tomography. The mechanical properties and cytocompatibility of the new scaffold composition were also evaluated. The addition of bioglass to the Alg/HAp network resulted in a slightly lower porosity. However, despite the change in pore size, the MG-63 cells were able to better adhere and proliferate when cultured for one week on a BG scaffold compared to the control Alg/HAp scaffolds. Thus, our findings indicate that the combination of bioactive glass BGMS10 does not affect the structural and physicochemical properties of the Alg/HAp scaffold and confers bioactive properties to the structures, making the Alg/HAp-BGMS10 scaffold a promising candidate for future application in bone tissue regeneration.

Current and Future Perspectives of Bioactive Glasses as Injectable Material.

This review covers recent compositions of bioactive glass, with a specific emphasis on both inorganic and organic materials commonly utilized as matrices for injectable materials. The major objective is to highlight the predominant bioactive glass formulations and their clinical applications in the biomedical field. Previous studies have highlighted the growing interest among researchers in bioactive glasses, acknowledging their potential to yield promising outcomes in this field. As a result of this increased interest, investigations into bioactive glass have prompted the creation of composite materials and, notably, the development of injectable composites as a minimally invasive method for administering the material within the human body. Injectable materials have emerged as a promising avenue to mitigate various challenges. They offer several advantages, including minimizing invasive surgical procedures, reducing patient discomfort, lowering the risk of postoperative infection and decreasing treatment expenses. Additionally, injectable materials facilitate uniform distribution, allowing for the filling of defects of any shape.