Zinc- and Copper-Doped Mesoporous Borate Bioactive Glasses: Promising Additives for Potential Use in Skin Wound Healing Applications.

In this study, zinc (Zn)- and copper (Cu)-doped 13-93B3 borate mesoporous bioactive glasses (MBGs) were successfully synthesized using nitrate precursors in the presence of Pluronic P123. We benefited from computational approaches for predicting and confirming the experimental findings. The changes in the dynamic surface tension (SFT) of simulated body fluid (SBF) were investigated using the Du Noüy ring method to shed light on the mineralization process of hydroxyapatite (HAp) on the glass surface. The obtained MBGs were in a glassy state before incubation in SBF. The formation of an apatite-like layer on the SBF-incubated borate glasses was investigated by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The incorporation of Zn and Cu into the basic composition of 13-93B3 glass led to changes in the glass transition temperature (Tg) (773 to 556 °C), particle size (373 to 64 nm), zeta potential (−12 to −26 mV), and specific surface area (SBET) (54 to 123 m2/g). Based on the K-means algorithm and chi-square automatic interaction detection (CHAID) tree, we found that the SFT of SBF is an important factor for the prediction and confirmation of the HAp mineralization process on the glasses. Furthermore, we proposed a simple calculation, based on SFT variation, to quantify the bioactivity of MBGs. The doped and dopant-free borate MBGs could enhance the proliferation of mouse fibroblast L929 cells at a concentration of 0.5 mg/mL. These glasses also induced very low hemolysis (<5%), confirming good compatibility with red blood cells. The results of the antibacterial test revealed that all the samples could significantly decrease the viability of Pseudomonas aeruginosa. In summary, we showed that Cu-/Zn-doped borate MBGs can be fabricated using a cost-effective method and also show promise for wound healing/skin tissue engineering applications, as especially supported by the cell test with fibroblasts, good compatibility with blood, and antibacterial properties.

Antioxidant Effects of Bioactive Glasses (BGs) and Their Significance in Tissue Engineering Strategies.

Elevated levels of oxidative stress are usually observed following injuries, leading to impaired tissue repair due to oxidation-related chronic inflammation. Several attempts have been made to manage this unfavorable situation, and the use of biomaterials with antioxidant activity is showing great promise in tissue engineering and regenerative medicine approaches. Bioactive glasses (BGs) are a versatile group of inorganic substances that exhibit an outstanding regenerative capacity for both hard and soft damaged tissues. The chemical composition of BGs provides a great opportunity for imparting specific biological activities to them. On this point, BGs may easily become antioxidant substances through simple physicochemical modifications. For example, particular antioxidant elements (mostly cerium (Ce)) can be added to the basic composition of the glasses. On the other hand, grafting natural antioxidant substances (e.g., polyphenols) on the BG surface is feasible for making antioxidant substitutes with promising results in vitro. Mesoporous BGs (MBGs) were demonstrated to have unique merits compared with melt-derived BGs since they make it possible to load antioxidants and deliver them to the desired locations. However, there are actually limited in vivo experimental studies on the capability of modified BGs for scavenging free radicals (e.g., reactive oxygen species (ROS)). Therefore, more research is required to determine the actual potential of BGs in decreasing oxidative stress and subsequently improving tissue repair and regeneration. The present work aims to highlight the potential of different types of BGs in modulating oxidative stress and subsequently improving tissue healing.

Modified Sol-Gel Synthesis of Mesoporous Borate Bioactive Glasses for Potential Use in Wound Healing.

In this study, we successfully utilized nitrate precursors for the synthesis of silver (Ag)-doped borate-based mesoporous bioactive glass (MBGs) based on the 1393B3 glass formulation in the presence of a polymeric substrate (polyvinyl alcohol (PVA)) as a stabilizer of boric acid. The X-ray diffraction (XRD) analysis confirmed the glassy state of all the MBGs. The incorporation of 7.5 mol% Ag into the glass composition led to a decrease in the glass transition temperature (Tg). Improvements in the particle size, zeta potential, surface roughness, and surface area values were observed in the Ag-doped MBGs. The MBGs (1 mg/mL) had no adverse effect on the viability of fibroblasts. In addition, Ag-doped MBGs exhibited potent antibacterial activity against gram-positive and gram-negative species. In summary, a modified sol-gel method was confirmed for producing the Ag-doped 1393B3 glasses, and the primary in vitro outcomes hold promise for conducting in vivo studies for managing burns.

Hydroxyapatite Nanoparticles for Improved Cancer Theranostics.

Beyond their well-known applications in bone tissue engineering, hydroxyapatite nanoparticles (HAp NPs) have also been showing great promise for improved cancer therapy. The chemical structure of HAp NPs offers excellent possibilities for loading and delivering a broad range of anticancer drugs in a sustained, prolonged, and targeted manner and thus eliciting lower complications than conventional chemotherapeutic strategies. The incorporation of specific therapeutic elements into the basic composition of HAp NPs is another approach, alone or synergistically with drug release, to provide advanced anticancer effects such as the capability to inhibit the growth and metastasis of cancer cells through activating specific cell signaling pathways. HAp NPs can be easily converted to smart anticancer agents by applying different surface modification treatments to facilitate the targeting and killing of cancer cells without significant adverse effects on normal healthy cells. The applications in cancer diagnosis for magnetic and nuclear in vivo imaging are also promising as the detection of solid tumor cells is now achievable by utilizing superparamagnetic HAp NPs. The ongoing research emphasizes the use of HAp NPs in fabricating three-dimensional scaffolds for the treatment of cancerous tissues or organs, promoting the regeneration of healthy tissue after cancer detection and removal. This review provides a summary of HAp NP applications in cancer theranostics, highlighting the current limitations and the challenges ahead for this field to open new avenues for research.

Preparation and Characterization of Platelet Lysate (Pl)-Loaded Electrospun Nanofibers for Epidermal Wound Healing.

Skin defects are among the most prevalent and serious problems worldwide; it is necessary to provide appropriate coverage in order to reduce possible mortality risk and accelerate wound healing. In this study, we have designed a series of extracellular matrix (ECM)-mimicking nanofibrous scaffolds composed of both natural (gelatin (GEL) and chitosan (CS)) and synthetic (poly(ε-caprolactone) (PCL) and poly (vinyl alcohol) (PVA)) polymers. The 3D constructs (PCL/GEL-PVA/CS) were reinforced with 5% (w/w) of platelet lysate (PL) for promoting cells viability and mobility. The physicochemical characterizations of nanofibers confirmed suitable hydrophilicity, controlled degradability, and water uptake of 250.31 ± 62.74%, and 222.425 ± 86.37% for the PCL/GEL-PVA/CS and PCL/GEL-PVA/CS + PL nanofibers, respectively. The scanning electron microscopy (SEM) images exhibited the mean diameter of the fabricated fibers (PCL/GEL-PVA/CS) in the range of 454 ± 257 nm. The blended samples (PCL/GEL-PVA/CS) were also confirmed to have higher ultimate tensile stress (UTS) (3.71 ± 0.32 MPa). From a biological point of view, the fabricated scaffolds showed appropriate blood compatibility and great potential to avoid bacterial invasion. Altogether, the tailored fabrication of PCL/GEL-PVA/CS nanofibers may be considered a suitable construct for epidermal wound healing.

Iron (Fe)-doped mesoporous 45S5 bioactive glasses: Implications for cancer therapy.

The utilization of bioactive glasses (BGs) in cancer therapy has recently become quite promising; herein, a series of Fe-doped mesoporous 45S5-based BGs (MBGs) were synthesized via the sol-gel method in the presence of Pluronic P123 as a soft template. The physico-chemical and biological properties of the prepared glasses were well-characterized through structural assessments, thermal analyses, and electron microscopic studies. Electrochemical analyses, including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), were also performed to investigate the actual potential of the Fe2O3-containing MBGs in modulating the Fenton's reaction. The XRD results confirmed the glassy state of the Fe-doped samples before immersion in simulated body fluid (SBF). The prepared Fe-doped MBGs exhibited a particle size in the range of 11-86 nm, surface charge of 27-30 mV, SBET of 95-306 m2/g, and Ms of 0.08 to 0.2 emu/g. The incorporation of Fe2O3 led to a negligible decrease in the bioactivity of the glasses. The CV analysis indicated that the Fe-doped MBGs could generate H2O2 in a cathodic potential higher than -0.2 V (vs. Ag/AgCl) in the O2-saturated Na2SO4 solution. Additionally, the data of the EIS test revealed that the Fe2O3-doped MBGs could increase the standard rate constant of Electro-Fenton's (EF) reaction up to 38.44 times as compared with the Fe-free glasses. In conclusion, Fe-doped 45S5-derived glasses may be useful in cancer therapy strategies due to their capability of activating Fenton's reaction and subsequent production of reactive oxygen species (ROS) such as •OH free radicals.

Osteogenic Potential of Magnesium (Mg)-Doped Multicomponent Bioactive Glass: In Vitro and In Vivo Animal Studies.

The use of bioactive glasses (BGs) has been quite fruitful in hard tissue engineering due to the capability of these materials to bond to living bone. In this work, a melt-derived magnesium (Mg)-doped BG (composition: 45SiO2-3P2O5-26CaO-15Na2O-7MgO-4K2O (mol.%)) was synthesized for being used in bone reconstruction. The prepared BGs were then manufactured as three-dimensional (3D) scaffolds by using the sponge replica approach. The microstructure of the samples was assessed by X-ray diffraction (XRD) and the surface morphology was observed by using scanning electron microscopy (SEM). The in vitro bioactivity and the release of osteo-stimulatory Mg2+ ions from the prepared samples were investigated over 7 days of incubation in simulated body fluids (SBF). In vitro cellular analyses revealed the compatibility of the Mg-doped BGs with human osteosarcoma cells (MG-63 cell line). Moreover, the Mg-doped BGs could induce bone nodule formation in vitro and improve the migratory ability of human umbilical vein endothelial cells (HUVECs). In vivo osteogenic capacity was further evaluated by implanting the BG-derived scaffolds into surgically-created critical-size bone defects in rats. Histological and immunohistological observations revealed an appropriate bone regeneration in the animals receiving the glass-based scaffolds after 12 weeks of surgery. In conclusion, our study indicates the effectiveness of the Mg-doped BGs in stimulating osteogenesis in both in vitro and in vivo conditions.

Improved osteogenesis and angiogenesis of theranostic ions doped calcium phosphates (CaPs) by a simple surface treatment process: A state-of-the-art study.

Surface treatment of biomaterials could enable reliable and quick cellular responses and accelerate the healing of the host tissue. Here, a series of calcium phosphates (CaPs) were surface treated by hydrogen peroxide (H2O2) and the treatment effects were physicochemically and biologically evaluated. For this aim, as-synthesized CaPs doped with strontium (Sr2+), iron (Fe2+), silicon (Si4+), and titanium (Ti4+) ions were sonicated in H2O2 media. The results showed that the specific surface area and zeta potential values of the surface-treated CaPs were increased by ~50% and 25%, respectively. Moreover, the particle size and the band-gap (Eg) values of the surface-treated CaPs were decreased by ~25% and ~2-10%, respectively. The concentration of oxygen vacancies was increased in the surface-treated samples, which was confirmed by the result of ultraviolet (UV), photoluminescence (PL), Commission Internationale de l'éclairage (CIE 1931), and X-ray photoelectron spectroscopy (XPS) analyses. In vitro cellular assessments of surface-treated CaPs exhibited an improvement in cytocompatibility, reactive oxygen species generation (ROS) capacity, bone nodule formation, and the migration of cells up to ~8%, 20%, 35%, and 13%, respectively. Based on the obtained data, it can be stated that improved physicochemical properties of H2O2-treated CaPs could increase the ROS generation and subsequently enhance the biological activities. In summary, the results demonstrate the notable effect of the H2O2 surface treatment method on improving surface properties and biological performance of CaPs.

Effect of photodynamic therapy on expression of HRAS, NRAS and caspase 3 genes at mRNA levels, apoptosis of head and neck squamous cell carcinoma cell line.

OBJECTIVES: This study aimed to assess the effect of photodynamic therapy (PDT) on expression of CASP3, NRAS and HRAS genes at mRNA levels, and apoptosis of head and neck squamous cell carcinoma (HNSCC) cell line. MATERIALS AND METHODS: In order to complete the present in vitro study, HNSCC cell line (NCBI C196 HN5) purchased from Pasteur Institute. Cells were divided into four groups; Group 1: photodynamic treatment (laser + methylene blue (MB) as photosensitizer), group 2: MB, group 3: laser (with 660 nm wavelength), and group 4: control (without any treatment). To determine the optimal concentration of MB, in a pilot study, toxicity of MB in different concentration was assessed using MTT assay. Cells in group 1, 2 and 3 was treated at optimal concentration of MB (1.6 µg/mL). Gene expression at mRNA levels was assessed after 24 h incubation, using real-time (qRT)-PCR. The expression of BAX and BCL2 genes at the mRNA levels was analyzed to evaluate apoptosis. 2-ΔΔCt values of BCL2, BAX, CASP3, NRAS, and HRAS in groups was analyzed using ANOVA. Tukey's HSD and Games Howell test was used to compare between two groups. RESULTS: Over-expression of BAX (p < 0.001), CASP3 (p < 0.001) and down-regulation of BCL2 (p = 0.004), HRAS (p = 0.023) and NRAS (p = 0.045) were noted in group 1 (PDT), compared with the control group. Treatment by laser alone induce down-regulation of CASP3 (p < 0.05), BAX (p < 0.05), BCL2 (p > 0.05), HRAS (p > 0.05) and NRAS (p > 0.05). CONCLUSION: PDT caused down-regulation of NRAS, HRAS and BCL2 and over-expression of CASP3 and BAX genes at mRNA levels in HNSCC cell line. The present study raises the possibility that the role of MB on BCL2 down-regulation and BAX and CASP3 over-expression was higher than laser alone while it seems that laser alone was more effective than MB in HRAS and NRAS down-regulation.

Strontium- and Cobalt-Doped Multicomponent Mesoporous Bioactive Glasses (MBGs) for Potential Use in Bone Tissue Engineering Applications.

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.

Functionalization and Surface Modifications of Bioactive Glasses (BGs): Tailoring of the Biological Response Working on the Outermost Surface Layer.

Bioactive glasses (BGs) are routinely being used as potent materials for hard and soft tissue engineering applications; however, improving their biological activities through surface functionalization and modification has been underestimated so far. The surface characteristics of BGs are key factors in determining the success of any implanted BG-based material in vivo since they regulate the affinity and binding of different biological macromolecules and thereby the interactions between cells and the implant. Therefore, a number of strategies using chemical agents (e.g., glutaraldehyde, silanes) and physical methods (e.g., laser treatment) have been evaluated and applied to design properly, tailor, and improve the surface properties of BGs. All these approaches aim at enhancing the biological activities of BGs, including the induction of cell proliferation and subsequent osteogenesis, as well as the inhibition of bacterial growth and adhesion, thereby reducing infection. In this study, we present an overview of the currently used approaches of surface functionalization and modifications of BGs, along with discussing the biological outputs induced by these changes.

Synthesis of nano HA/ßTCP mesoporous particles using a simple modification in granulation method.

Granulation method in the mixture of oil, water, and polymer was used to synthesize HA/ßTCP porous nano-powders. The effects of different types of polymeric-substrate, drying process, and thermal heat-treatment on the crystallization process of calcium phosphate nano-particles were studied. As-synthesized particles were treated with different chemical surface agents to improve their surface charge, cell growth, and cell adhesion properties. X-ray diffraction (XRD) and Brunauer-Emmett-Teller (BET) analyses were employed to explore the phase composition and specific surface area of synthesized powders, respectively. Results showed that the presence of oil in PVA/oil system results in crystallization of mesoporous HA/ßTCP particles with the surface area of 93 cm2/g, while using gelatin/oil mixture leads to crystallization of pure HA nano-particles with the surface area of 115 cm2/g. Using Rietveld method, the amounts of HA/ßTCP and amorphous phases in the oven-dried PVA substrated powders after heat-treatment were calculated as about 65, 13, and 22 wt%, respectively. Interfacial tension energy (IFT) results indicated that PVA could reduce interfacial tension energy of oil/water mixture from 21.6 mN/m to 7.0 mN/m. The ZETA potential measurements showed that using 25 wt% of tetraethyl orthosilicate (TEOS) as surface modifier could increase zeta values from -21 ±â€¯1 to -42 ±â€¯1 mV. According to cell viability results, synthesized powder in the presence of oil/PVA, which was then modified by 25 wt% of TEOS, did not cause toxicity. Using Alizarin Red S staining quantification assay, it was found that after modification by TEOS, bone-nodule formation was enhanced by 25%. Furthermore, cell adhesion of the TEOS-modified surface was found to be significantly higher than that of non-modified one. Altogether, granulation method successfully led to improvement of synthesized porous HA/ßTCP nanoparticles' physio-chemical properties.