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Bioactive glasses (BGs) have shown great potential for tissue regeneration and their composition flexibility allows the incorporation of different ions with physiological activities and therapeutic properties in the glass network. Among the many ions that could be incorporated, cobalt (Co) is a significant one, as it mimics hypoxia, triggering the formation of new blood vessels by the vascular endothelial growth factor A (VEGFA), due to the stabilizing effect on the hypoxia inducible factor 1 subunit alpha (HIF1A), an activator of angiogenesis-related genes, and is therefore of great interest for tissue engineering applications. However, despite its promising properties, the effects of glasses incorporated with Co on angiogenesis, through human umbilical cord vein endothelial cells (HUVECs) studies, need to be further investigated. Therefore, this work aimed to evaluate the biocompatibility and angiogenic potential of a new sol-gel BG, derived from the SiO 2 -CaO-P 2 O 5 -CoO system. The structural evaluation showed the predominance of an amorphous glass structure, and the homogeneous presence of cobalt in the samples was confirmed. in vitro experiments showed that Co-containing glasses did not affect the viability of HUVECs, stimulated the formation of tubes and the gene expression of HIF1A and VEGFA. in vivo experiments showed that Co-containing glasses stimulated VEGFA and HIF1A expression in blood vessels and cell nuclei, respectively, in the deep dermis layer of the dorsal region of rats, featuring considerable local stimulation of the angiogenesis process due to Co-release. Co-containing glasses showed therapeutic effect, and Co incorporation is a promising strategy for obtaining materials with superior angiogenesis properties for tissue engineering applications., (© 2020 Wiley Periodicals LLC.)

The aim of this study was to investigate the influence of copper (Cu) on bioactivity and on the pathogen inhibition of bioactive glasses (BG) doped with CuO. The BG samples were prepared using a sol-gel method with a molar composition of 55SiO2-(42.5-x) CaO-2.5P2O5-xCuO, where x represents the CuO concentration (0, 1, and 2 mol%). The bioactivity of the glasses was evaluated by immersing them in simulated body fluid (SBF) for 7 and 15 days. Thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron microscopy (SEM) were employed to assess the bioactive behavior of the glasses. The results revealed that the bioactive glass doped with 2 mol% CuO exhibited enhanced biocompatibility, as evidenced by the accelerated formation of a hydroxyapatite layer. Furthermore, 29Si and 31P nuclear magnetic resonance (NMR) analysis provided insights into the connectivity of the bioactive glass network upon copper addition. Additionally, an antibacterial test was conducted against Bacillus subtilis, a common pathogen. The results demonstrated that the copper-doped bioactive glass exhibited significant antibacterial activity against Bacillus subtilis, highlighting its potential for promoting the regeneration of hard tissues. Overall, this study contributes to a better understanding of the effects of copper on the bioactivity and antibacterial properties of a new composition of bioactive glasses, which could have important implications in biomedical applications. Highlights: Cu-doped bioactive glass promoted tissue regeneration and exhibited antibacterial properties. NMR analysis enhanced understanding of copper's impact on glass network connectivity. Cu-doped bioactive glass demonstrated significant antibacterial activity against Bacillus subtilis, suggesting potential for biomedical applications. [ABSTRACT FROM AUTHOR]

The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain. [ABSTRACT FROM AUTHOR]

Injectable in situ-forming scaffolds that induce both angiogenesis and osteogenesis have been proven to be promising for bone healing applications. Here, we report the synthesis of an injectable hydrogel containing cobalt-doped bioactive glass (BG)-loaded microspheres. Silk fibroin (SF)/gelatin microspheres containing BG particles were fabricated through microfluidics. The microspheres were mixed in an injectable alginate solution, which formed an in situ hydrogel by adding CaCl 2 . The hydrogel was evaluated for its physicochemical properties, in vitro interactions with osteoblast-like and endothelial cells, and bone healing potential in a rat model of calvarial defect. The microspheres were well-dispersed in the hydrogel and formed pores of >100 μm. The hydrogel displayed shear-thinning behavior and modulated the cobalt release so that the optimal cobalt concentration for angiogenic stimulation, cell proliferation, and deposition of mineralized matrix was only achieved by the scaffold that contained BG doped with 5% wt/wt cobalt (A-S-G5Co). In the scaffold containing higher cobalt content, a reduced biomimetic mineralization on the surface was observed. The gene expression study indicated an upregulation of the osteogenic genes of COL1A1, ALPL, OCN, and RUNX2 and angiogenic genes of HIF1A and VEGF at different time points in the cells cultured with the A-S-G5Co. Finally, the in vivo study demonstrated that A-S-G5Co significantly promoted both angiogenesis and osteogenesis and improved bone healing after 12 weeks of follow-up. These results show that incorporation of SF/gelatin microspheres containing cobalt-doped BG in an injectable in situ-forming scaffold can effectively enhance its bone healing potential through promotion of angiogenesis and osteogenesis., (© 2024 Wiley Periodicals LLC.)

Purpose: Due to the multilayered structure of the skin tissue, the architecture of its engineered scaffolds needs to be improved. In the present study, 45s5 bioglass nanoparticles were selected to induce fibroblast proliferation and their protein secretion, although cobalt ions were added to increase their potency. Methods: A 3-layer scaffold was designed as polyurethane (PU) - polycaprolactone (PCL)/ collagen/nanoparticles-PCL/collagen. The scaffolds examined by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), tensile, surface hydrophilicity and weight loss. Biological tests were performed to assess cell survival, adhesion and the pattern of gene expression. Results: The mechanical assay showed the highest young modulus for the scaffold with the doped nanoparticles and the water contact angle of this scaffold after chemical crosslinking of collagen was reduced to 52.34±7.7°. In both assessments, the values were statistically compared to other groups. The weight loss of the corresponding scaffold was the highest value of 82.35±4.3 % due to the alkaline effect of metal ions and indicated significant relations in contrast to the scaffold with non-doped particles and bare one (P value<0.05). Moreover, better cell expansion, greater cell confluence and a lower degree of toxicity were confirmed. The up-regulation of TGF β1 and VEGF genes introduced this scaffold as a better model for the fibroblasts commitment to a new skin tissue among bare and nondoped scaffold (P value<0.05). Conclusion: The 3-layered scaffold which is loaded with cobalt ions-bonded bioglass nanoparticles, is a better substrate for the culture of the fibroblasts. [ABSTRACT FROM AUTHOR]

The current research was done to evaluate the effect of zinc on the structural and biological characteristics of 58 s bioactive glasses. To this end, SiO2–CaO–P2O5–SrO–ZnO bioactive nanoglasses containing different content of ZnO (0, 1, 3, and 5 mol.%) were produced by the sol–gel process. To assess their bioactivity, the specimens were soaked in the simulated body fluid (SBF) solution for 21 days and analyzed employing Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction (XRD), and scanning electron microscopy (SEM) techniques. The results indicated that the bioactive nanoglass sample containing 1 mol.% Zn possessed the highest potential in terms of hydroxyapatite formation. The results obtained by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay proved the superior biocompatibility of Zn-containing nanoglasses compared to Zn-free samples. Accordingly, the sample containing 1 mol.% Zn was considered a suitable candidate for medical applications. [ABSTRACT FROM AUTHOR]

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There is an ongoing profound shift in using glass as a primarily passive material to one that instills active properties. We believe and demonstrate that bioactive glasses (BGs) and glass–ceramics (BGCs) as functional biomaterials for cancer therapy can transform the world of healthcare in the 21st century. Melt/gel‐derived BGs and BGCs can carry many exotic elements, including less common rare‐earth, and trigger highly efficient anticancer properties via the combination of radiotherapy, photothermal therapy, magnetic hyperthermia, along with drug or therapeutic ions delivery. The addition of these dopants modifies the bioactivity, imparts novel functionalities, and induces specific biological effects that are not achievable using other classes of biomaterials. In this paper, we have briefly reviewed and discussed the current knowledge on promising compositions, processing parameters, and applications of BGs and BGCs in treating cancer. We also envisage the need for further research on this particular, unique class of BGs and BGCs. [ABSTRACT FROM AUTHOR]

Thermosensitive injectable hydrogels are widely investigated as a minimally invasive tool for the delivery of therapeutic agents. Here, Pluronic F-127 hydrogels containing mesoporous bioactive glass nanoparticles were obtained as a novel device to improve bone tissue regeneration. Thermosensitive behavior and injectability of the obtained nanocomposites hydrogels were evaluated, showing feasibility for minimally invasive administration and sol–gel phase transition in the range of 18 to 23 °C, suitable for use as an injectable system. Rheological evaluation showed that adding bioactive glass improved the hydrogel elastic properties and stability at body temperature, also increasing the storage modulus (G') and residence time. The injectability evaluation showed that all formulations were able to be administrated using a maximum force of up to 2.4 ± 0.4 N, compatible with manual injection. The results shows that Pluronic F-127/mesoporous bioactive glass systems are potential candidates to be applied as injectable systems for therapeutic agents release in situ. [ABSTRACT FROM AUTHOR]

Designing scaffolds with therapeutic potential to stimulate angiogenesis and osteogenesis is considered a promising strategy in the regeneration of large skeletal defects. In this study, the cobalt ions (Co2+) were incorporated in laponite (LAP) nanodiscs (0.65, 1.3, and 2.6 g/L) and, in combination with carboxymethyl chitosan (CMC), were immobilized on the electrospun polycaprolactone (PCL) nanofiber to fabricate scaffolds for simultaneous enhancing osteogenesis and angiogenesis inductions to human bone marrow mesenchymal stem cells. The Fourier transform infrared, energy dispersive X‐ray, and inductively coupled plasma atomic emission spectrometries confirmed the Co2+‐loading on the LAP nanodiscs and the chemical immobilization on the surface of PCL nanofibers. The result of MTT assay, scanning electron microscopy, and fluorescence staining displayed that Co2+‐loaded scaffolds were biocompatible. Furthermore, the incorporation of Co2+ ions into LAP nanodiscs had significant effects on the calcium deposition and expression of osteogenic markers, alkaline phosphatase and osteonectin, as well as, the expression of angiogenic markers, hypoxia‐inducible factor‐1α and vascular endothelial growth factor of the cells seeded on the scaffolds (p ≤ 0.05). These results suggested that the combination of Co2+ ions with CMC/LAP could result in a synergetic effect on the osteogenesis and angiogenesis stimulations. [ABSTRACT FROM AUTHOR]

Bioactive glasses (BGs) have shown great potential for tissue regeneration and their composition flexibility allows the incorporation of different ions with physiological activities and therapeutic properties in the glass network. Among the many ions that could be incorporated, cobalt (Co) is a significant one, as it mimics hypoxia, triggering the formation of new blood vessels by the vascular endothelial growth factor A (VEGFA), due to the stabilizing effect on the hypoxia inducible factor 1 subunit alpha (HIF1A), an activator of angiogenesis‐related genes, and is therefore of great interest for tissue engineering applications. However, despite its promising properties, the effects of glasses incorporated with Co on angiogenesis, through human umbilical cord vein endothelial cells (HUVECs) studies, need to be further investigated. Therefore, this work aimed to evaluate the biocompatibility and angiogenic potential of a new sol–gel BG, derived from the SiO2–CaO–P2O5–CoO system. The structural evaluation showed the predominance of an amorphous glass structure, and the homogeneous presence of cobalt in the samples was confirmed. in vitro experiments showed that Co‐containing glasses did not affect the viability of HUVECs, stimulated the formation of tubes and the gene expression of HIF1A and VEGFA. in vivo experiments showed that Co‐containing glasses stimulated VEGFA and HIF1A expression in blood vessels and cell nuclei, respectively, in the deep dermis layer of the dorsal region of rats, featuring considerable local stimulation of the angiogenesis process due to Co‐release. Co‐containing glasses showed therapeutic effect, and Co incorporation is a promising strategy for obtaining materials with superior angiogenesis properties for tissue engineering applications. [ABSTRACT FROM AUTHOR]

Hybrid scaffolds appear as a promising strategy to accelerate bone tissue repair due to their biocompatibility and to combine physical, mechanical and biological characteristics similar to those of human bone tissue. However, there are no studies in hybrid scaffolds using the sol–gel method and a foaming system, with the direct incorporation of cobalt therapeutic ion. In this work, novel porous polyvinyl alcohol polymer (PVA)/bioactive glasses (BG) hybrids scaffolds containing cobalt were obtained, combining the PVA non-toxicity, non-carcinogenicity and processability to the BG bioactivity and osteogenic properties and Co angiogenic effect by the sol–gel and foaming processing method, in order to obtain a new scaffold with angiogenic properties. The effects of Co incorporation on scaffold structure, bioactivity and ion release were evaluated. Cell viability and cell growth assay were performed on human umbilical vein endothelial cells, demonstrating excellent mitochondrial activity without cytotoxicity and cell-friendly environment. Hybrid scaffolds supported fast ion release and an elastic modulus of 20.19 MPa. The presence of cobalt was confirmed by SEM and EDS. Co-incorporated samples showed high porosity and favorable pore size. PVA–BG hybrid scaffolds containing Co showed ionic release rate in the therapeutic range and are promising for angiogenesis in tissue engineering applications. [ABSTRACT FROM AUTHOR]

Bioactive glasses (BGs) are widely used for bone regeneration, and allow the incorporation of different ions with therapeutic properties into the glass network. Amongst the different ions with therapeutic benefits, manganese (Mn) has been shown to influence bone metabolism and activate human osteoblasts integrins, improving cell adhesion, proliferation and spreading. Mn has also been incorporated into bioceramics as a therapeutic ion for improved osteogenesis. Here, up to 4.4 mol% MnO was substituted for CaO in the 58S composition (60 mol% SiO2, 36 mol% CaO, 4 mol% P2O5) and its effects on the glass properties and capability to influence the osteogenic differentiation were evaluated. Mn-containing BGs with amorphous structure, high specific surface area and nanoporosity were obtained. The presence of Mn2+ species was confirmed by X-ray photoelectron spectroscopy (XPS). Mn-containing BGs presented no cytotoxic effect on human mesenchymal stem cells (hMSCs) and enabled sustained ion release in culture medium. hMSCs osteogenic differentiation stimulation and influence on the mineralisation process was also confirmed through the alkaline phosphatase (ALP) activity, and expression of osteogenic differentiation markers, such as collagen type I, osteopontin and osteocalcin, which presented higher expression in the presence of Mn-containing samples compared to control. Results show that the release of manganese ions from bioactive glass provoked human mesenchymal stem cell (hMSC) differentiation down a bone pathway, whereas hMSCs exposed to the Mn-free glass did not differentiate. Mn incorporation offers great promise for obtaining glasses with superior properties for bone tissue regeneration. [ABSTRACT FROM AUTHOR]