A ternary composite hydrogel based on sodium alginate, carboxymethyl cellulose and copper-doped 58S bioactive glass promotes cutaneous wound healing in vitro and in vivo.

Hydrogels offer a novel approach to wound repair. In this study, we synthesized a ternary composite using sodium alginate (SA), carboxymethyl cellulose (CMC) and copper-doped 58S bioactive glass (BG). According to our mechanical testing results, the composite made of 7 wt% CMC and 7 wt% BG (SA-7CMC-7BG) showed optimal properties. In addition, our in vitro studies revealed the biocompatibility and bioactivity of SA-7CMC-7BG, with a negative zeta potential of -31.7 mV. Scanning electron microscope (SEM) images showed 273-µm-diameter pores, cell adhesion, and anchoring. The SA-7CMC-7BG closed 90.4 % of the mechanical scratch after 2 days. An in vivo wound model using Wistar rats showed that SA-7CMC-7BG promoted wound healing, with 85.57 % of the wounds healed after 14 days. Treatment with the SA-7CMC-7BG hydrogel caused a 1.6-, 65-, and 1.87-fold increase in transforming growth factor beta (TGF-ß), Col I, and vascular endothelial growth factor (VEGF) expression, respectively that prevents fibrosis and promotes angiogenesis. Furthermore, interleukin 1ß (IL-1ß) expression was downregulated by 1.61-fold, indicating an anti-inflammatory effect of SA-7CMC-7BG. We also observed an increase in epidermal thickness, the number of fibroblast cells, and collagen deposition, which represent complementary pathology results confirming the effectiveness of the SA-7CMC-7BG hydrogel in cutaneous wound healing.

The impact of PEEK pretreatment using H2SO4, riboflavin, and aluminum trioxide on the extrusion bond strength to canal dentin luted with Polymethyl methacrylate and resin-based composite cement.

OBJECTIVE: To evaluate the effects of various surface pretreatment methods, including H2SO4, Riboflavin, and Al2O3, as well as different luting cement types, namely Methyl Methacrylate based Cement (MMBC) and composite-based cement (CBC), on the extrusion bond strength (EBS) of poly-ether-ether-ketone (PEEK) posts bonded to canal dentin. MATERIALS AND METHODS: This study involved 120 single-rooted human premolar teeth that underwent endodontic treatment. Following root canal preparation, PEEK posts were fabricated from PEEK blanks using a CAD-CAM system, resulting in a total of 120 posts. The posts were randomly assigned to one of four groups based on their post-surface conditioning: Group A H2SO4, Group B RF, Group C Al2O3, and Group D (NC), each consisting of 30 posts. Within each group, there were two subgroups based on the type of luting cement used for bonding. Subgroups A1, B1, C1, and D1 (n=15 each) utilized CBC, while Subgroups A2, B2, C2, and D2 (n=15 each) used MMBC.The bond strength between the PEEK posts and root dentin was assessed using a universal testing machine, and the failure modes were examined under a stereomicroscope. Statistical analysis, including one-way analysis of variance (ANOVA) and Tukey's Post Hoc test with a significance level of p=0.05, was performed to analyze the data and evaluate the effects of surface treatment and luting cement type on the bond strength. RESULTS: Group B2, which underwent RF conditioning followed by Super-Bond C&B cement application, exhibited the highest bond strength scores at the coronal section (9.57±0.67 MPa). On the other hand, Group D1, which had no conditioning (NC) and used Panavia® V5 cement, showed the lowest EBS at the apical third (2.39±0.72 MPa). The overall results indicate that the different conditioning regimens and luting cement types did not significantly influence the bond strength of PEEK posts to root dentin (p>0.05). CONCLUSIONS: Riboflavin activated by photodynamic therapy (PDT) and H2SO4 can be effective surface conditioners for PEEK posts. These treatments have shown potential for enhancing the bond strength between PEEK and resin cement. Additionally, the study revealed that MMA-based cement outperformed composite-based cement in terms of bond integrity with PEEK posts.

Selenium-Doped Mesoporous Bioactive Glass Regulates Macrophage Metabolism and Polarization by Scavenging ROS and Promotes Bone Regeneration In Vivo.

Bone regeneration is complex and involves multiple cells and systems, with macrophage-mediated immune regulation being critical for the development and regulation of inflammation, angiogenesis, and osteogenesis. Biomaterials with modified physical and chemical properties (e.g., modified wettability and morphology) effectively regulate macrophage polarization. This study proposes a novel approach to macrophage-polarization induction and -metabolism regulation through selenium (Se) doping. We synthesized Se-doped mesoporous bioactive glass (Se-MBG) and demonstrated its macrophage-polarization regulation toward M2 and its enhancement of the macrophage oxidative phosphorylation metabolism. The underlying mechanism is the effective scavenging of excessive intracellular reactive oxygen species (ROS) by the Se-MBG extracts through the promotion of peroxide-scavenging enzyme glutathione peroxidase 4 expression in the macrophages; this, in turn, improves the mitochondrial function. Printed Se-MBG scaffolds were implanted into rats with critical-sized skull defects to evaluate their immunomodulatory and bone regeneration capacity in vivo. The Se-MBG scaffolds demonstrated excellent immunomodulatory function and robust bone regeneration capacity. Macrophage depletion with clodronate liposomes impaired the Se-MBG-scaffold bone regeneration effect. Se-mediated immunomodulation, which targets ROS scavenging to regulate macrophage metabolic profiles and mitochondrial function, is a promising concept for future effective biomaterials for bone regeneration and immunomodulation.

Nanostructured bioactive glasses: A bird's eye view on cancer therapy.

Bioactive glasses (BGs) arewell known for their successful applications in tissue engineering and regenerative medicine. Recent experimental studies have shown their potential usability in oncology, either alone or in combination with other biocompatible materials, such as biopolymers. Direct contact with BG particles has been found to cause toxicity and death in specific cancer cells (bone-derived neoplastic stromal cells) in vitro. Nanostructured BGs (NBGs) can be doped with anticancer elements, such as gallium, to enhance their toxic effects against tumor cells. However, the molecular mechanisms and intracellular targets for anticancer compositions of NBGs require further clarification. NBGs have been successfully evaluated for use in various well-established cancer treatment strategies, including cancer hyperthermia, phototherapy, and anticancer drug delivery. Existing results indicate that NBGs not only enhance cancer cell death, but can also participate in the regeneration of lost healthy tissues. However, the application of NBGs in oncology is still in its early stages, and numerous unanswered questions must be addressed. For example, the impact of the composition, biodegradation, size, and morphology of NBGs on their anticancer efficacy should be defined for each type of cancer and treatment strategy. Moreover, it should be more clearly assessed whether NBGs can shrink tumors, slow/stop cancer progression, or cure cancer completely. In this regard, the use of computational studies (in silico methods) is highly recommended to design the most effective glass formulations for cancer therapy approaches and to predict, to some extent, the relevant properties, efficacy, and outcomes. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Nanodevices based on mesoporous glass nanoparticles enhanced with zinc and curcumin to fight infection and regenerate bone.

Nanotechnology-based approaches are emerging as promising strategies to treat different bone pathologies such as infection, osteoporosis or cancer. To this end, several types of nanoparticles are being investigated, including those based on mesoporous bioactive glasses (MGN) which exhibit exceptional structural and textural properties and whose biological behaviour can be improved by including therapeutic ions in their composition and loading them with biologically active substances. In this study, the bone regeneration capacity and antibacterial properties of MGNs in the SiO2-CaO-P2O5 system were evaluated before and after being supplemented with 2.5% or 4% ZnO and loaded with curcumin. in vitro studies with preosteoblastic cells and mesenchymal stem cells allowed determining the biocompatible MGNs concentrations range. Moreover, the bactericidal effect of MGNs with zinc and curcumin against S. aureus was demonstrated, as a significant reduction of bacterial growth was detected in both planktonic and sessile states and the degradation of a pre-formed bacterial biofilm in the presence of the nanoparticles also occurred. Finally, MC3T3-E1 preosteoblastic cells and S. aureus were co-cultured to investigate competitive colonisation between bacteria and cells in the presence of the MGNs. Preferential colonisation and survival of osteoblasts and effective inhibition of both bacterial adhesion and biofilm formation of S. aureus in the co-culture system were detected. Our study demonstrated the synergistic antibacterial effect of zinc ions combined with curcumin and the enhancement of the bone regeneration characteristics of MGNs containing zinc and curcumin to obtain systems capable of simultaneously promoting bone regeneration and controlling infection. STATEMENT OF SIGNIFICANCE: In search of a new approach to regenerate bone and fight infections, a nanodevice based on mesoporous SiO2-CaO-P2O5 glass nanoparticles enriched with Zn2+ ions and loaded with curcumin was designed. This study demonstrates the synergistic effect of the simultaneous presence of zinc ions and curcumin in the nanoparticles that significantly reduces the bacterial growth in planktonic state and is capable to degrade pre-formed S. aureus biofilms whereas the nanosystem exhibits a cytocompatible behaviour in the presence of preosteoblasts and mesenchymal stem cells. Based on these results, the designed nanocarrier represents a promising alternative for the treatment of acute and chronic infections in bone tissues, while avoiding the significant current problem of bacterial resistance to antibiotics.

Multifunctional Zn and Ag co-doped bioactive glass nanoparticles for bone therapeutic and regeneration.

Bone cancer has traditionally been treated using surgery, radiotherapy, and/or chemotherapy. The nonspecific distribution of chemotherapy and implantable infections are significant risk factors for the failure of the bone to heal. Multifunctional zinc and silver co-doped bioactive glass nanoparticles (yAg-xZn-BGNPs) with a diameter of 150 ± 30 nm were successfully synthesized using modified sol-gel and two-step post-functionalization processes, tailored to provide antibacterial and anticancer activity whilst maintaining osteogenesis ability. Co-doped BGNPs with Zn and Ag did not significantly alter physicochemical properties, including size, morphology, glass network, and amorphous nature. Apatite-like layer was observed on the surface of yAg-xZn-BGNPs and resorbed in the simulated body fluid solution, which could increase their bioactivity. Human fetal osteoblast cell line (hFOB 1.19) treated with particles showed calcified tissue formation and alkaline phosphatase activity in the absence of osteogenic supplements in vitro, especially with 0.5Ag-1Zn-BGNPs. Moreover, these particles preferentially disrupted the metabolic activity of bone cancer cells (MG-63) and had an antibacterial effect against B. subtilis, E. coli, and S. aureus via the disc diffusion method. This novel 0.5Ag-1Zn-BGNP and 1Ag-1Zn-BGNPs, with wide-ranging ability to stimulate bone regeneration, to inhibit bone cancer cell proliferation, and to prevent bacterial growth properties, may provide a feasible strategy for bone cancer treatment. The 0.5Ag-1Zn-BGNPs and 1Ag-1Zn-BGNPs can be applied for the preparation of scaffolds or filler composites using in bone tissue engineering.

Trends and perspectives on the commercialization of bioactive glasses.

At least 25 bioactive glass (BG) medical devices have been approved for clinical use by global regulatory agencies. Diverse applications include monolithic implants, bone void fillers, dentin hypersensitivity agents, wound dressing, and cancer therapeutics. The morphology and delivery systems of bioactive glasses have evolved dramatically since the first devices based on 45S5 Bioglass®. The particle size of these devices has generally decreased with the evolution of bioactive glass technology but primarily lies in the micron size range. Morphologies have progressed from glass monoliths to granules, putties, and cements, allowing medical professionals greater flexibility and control. Compositions of these commercial materials have primarily relied on silicate-based systems with varying concentrations of sodium, calcium, and phosphorus. Furthermore, therapeutic ions have been investigated and show promise for greater control of biological stimulation of genetic processes and increased bioactivity. Some commercial products have exploited the borate and phosphate-based compositions for soft tissue repair/regeneration. Mesoporous BGs also promise anticancer therapies due to their ability to deliver drugs in combination with radiotherapy, photothermal therapy, and magnetic hyperthermia. The objective of this article is to critically discuss all clinically approved bioactive glass products. Understanding essential regulatory standards and rules for production is presented through a review of the commercialization process. The future of bioactive glasses, their promising applications, and the challenges are outlined. STATEMENT OF SIGNIFICANCE: Bioactive glasses have evolved into a wide range of products used to treat various medical conditions. They are non-equilibrium, non-crystalline materials that have been designed to induce specific biological activity. They can bond to bone and soft tissues and contribute to their regeneration. They are promising in combating pathogens and malignancies by delivering drugs, inorganic therapeutic ions, and heat for magnetic-induced hyperthermia or laser-induced phototherapy. This review addresses each bioactive glass product approved by regulatory agencies for clinical use. A review of the commercialization process is also provided with insight into critical regulatory standards and guidelines for manufacturing. Finally, a critical evaluation of the future of bioactive glass development, applications, and challenges are discussed.

The influencing mechanism of phosphorus component on network structure and bioactivity of bioactive glass.

(64-x)SiO2-36CaO-xP2O5 (x = 0, 2, 4, 6, 8 mol%) bioactive glasses are successfully prepared by sol-gel method, and the effect of phosphorus (P) content on the network structure, phase composition and in vitro mineralization performance of bioactive glasses is investigated by the various characterization techniques. Results show that the as-prepared bioactive glass has the amorphous structure. With the increase of P content, it can be found in FT-IR spectra that the characteristic peaks of bending vibration corresponding to the P-O bond in PO43- gradually appear. Among, the typical 60S4P has the highest percentage (73.81%) of bridging oxygen (BO), indicating its highest aggregation degree of silicate network. Besides, the introduction of P2O5 results in the formation of monophosphate, which enable the bioactive glasses to dissolve rapidly in water or simulate body fluids (SBF) and crystallize to form hydroxyapatite (HA), thereby enhancing its biological activity. After soaking in SBF for 3 days, the irregular cauliflower-like HA particles appear on the surface of bioactive glass, and the appropriate amount of P addition in glass could result in its high bioactivity. Therefore, this study could provide a theoretical reference for the relationship between the network structure and bioactivity of bioactive glass.

Synthesis and Characterizations of Bioactive Glass Nanoparticle-Incorporated Triblock Copolymeric Injectable Hydrogel for Bone Tissue Engineering.

Recently, injectable hydrogels have attracted much interest in tissue engineering (TE) applications because of their controlled flowability, adaptability, and easy handling properties. This work emphasizes the synthesis and characterizations of bioactive glass (BAG) nanoparticle-reinforced poly(ethylene glycol) (PEG)- and poly(N-vinylcarbazole) (pNVC)-based minimally invasive composite injectable hydrogel suitable for bone regeneration. First, the copolymer was synthesized from a combination of PEG and pNVC through reversible addition-fragmentation chain-transfer (RAFT) polymerization and nanocomposite hydrogel constructs were subsequently prepared by conjugating BAG particles at varying loading concentrations. Gel permeation chromatography (GPC) analysis confirmed the controlled nature of the polymer. Various physicochemical characterization results confirmed the successful synthesis of copolymer and nanocomposite hydrogels that showed good gelling and injectability properties. Our optimal nanocomposite hydrogel formulation showed excellent swelling properties in comparison to the copolymeric hydrogel due to the presence of hydrophilic BAG particles. The bone cell proliferation rate was found to be evidently higher in the nanocomposite hydrogel than in the copolymeric hydrogel. Moreover, the enhanced level of ALP activity and apatite mineralization for the nanocomposite in comparison to that for the copolymeric hydrogel indicates accelerated in vitro osteogenesis. Overall, our study findings indicate BAG particle-conjugated nanocomposite hydrogels can be used as promising grafting materials in orthopedic reconstructive surgeries complementary to conventional bone graft substitutes in cancellous bone defects due to their 3D porous framework, minimal invasiveness, and ability to form any desired shape to match irregular bone defects.

Impact of Glass Irradiation on Laser-Induced Breakdown Spectroscopy Data Analysis.

Increased absorption of optical materials arising from exposure to ionizing radiation must be accounted for to accurately analyze laser-induced breakdown spectroscopy (LIBS) data retrieved from high-radiation environments. We evaluate this effect on two examples that mimic the diagnostics placed within novel nuclear reactor designs. The analysis is performed on LIBS data measured with 1% Xe gas in an ambient He environment and 1% Eu in a molten LiCl-KCl matrix, along with the measured optical absorption from the gamma- and neutron-irradiated low-OH fused silica and sapphire glasses. Significant changes in the number of laser shots required to reach a 3σ detection level are observed for the Eu data, increasing by two orders of magnitude after exposure to a 1.7 × 1017 n/cm2 neutron fluence. For all cases examined, the spectral dependence of absorption results in the introduction of systematic errors. Moreover, if lines from different spectral regions are used to create Boltzmann plots, this attenuation leads to statistically significant changes in the temperatures calculated from the Xe II lines and Eu II lines, lowering them from 8000 ± 610 K to 6900 ± 810 K and from 15,800 ± 400 K to 7200 ± 800 K, respectively, for exposure to the 1.7 × 1017 n/cm2 fluence. The temperature range required for a 95% confidence interval for the calculated temperature is also broadened. In the case of measuring the Xe spectrum, these effects may be mitigated using only the longer-wavelength spectral region, where radiation attenuation is relatively small, or through analysis using the iterative Saha-Boltzmann method.

Valorizing hazardous lead glass sludge and alumina flakes filling waste for the synthesis of geopolymer building bricks.

Geopolymer bricks from lead glass sludge (LGS) and alumina flakes filling (AFF) waste were synthesized in the present work. AFF waste was chemically treated to prepare sodium aluminate (NaAlO2) powder. Silicate source (untreated LGS and thermally treated one at 600 °C (LGS600)) and sodium oxide (Na2O) concentration (as NaAlO2) were the compositional parameters, which affected the physical and mechanical properties (compressive strength, water absorption, and bulk density) of the prepared bricks. High organic matter content inside LGS caused a retardation effect on the geopolymerization process, resulting in the formation of hardened bricks with modest 90-day compressive strengths (2.13 to 4.4 MPa). Using LGS600 enhanced the mechanical properties of the fabricated bricks, achieving a maximum 90-day compressive strength of 22.35 MPa at 3 wt.% Na2O. Sodium aluminosilicate hydrate was the main activation product inside all samples, as confirmed by X-ray diffraction and thermal analyses. Acetic acid leaching test also proved that all LGS600-NaAlO2 mixtures represented Pb concentrations in leachates lower than the permissible level of characteristic leaching procedures, indicating the mitigation of environmental problems caused by these wastes.

Magnetic bioactive glass nano-heterostructures: a deeper insight into magnetic hyperthermia properties in the scope of bone cancer treatment.

Primary bone cancers commonly involve surgery to remove the malignant tumor, complemented with a postoperative treatment to prevent cancer resurgence. Studies on magnetic hyperthermia, used as a single treatment or in synergy with chemo- or radiotherapy, have shown remarkable success in the past few decades. Multifunctional biomaterials with bone healing ability coupled with hyperthermia property could thus be of great interest to repair critical bone defects resulting from tumor resection. For this purpose, we designed superparamagnetic and bioactive nanoparticles (NPs) based on iron oxide cores (γ-Fe2O3) encapsulated in a bioactive glass (SiO2-CaO) shell. Nanometric heterostructures (122 ± 12 nm) were obtained through a two-step process: co-precipitation of 16 nm sized iron oxide NPs, followed by the growth of a bioactive glass shell via a modified Stöber method. Their bioactivity was confirmed by hydroxyapatite growth in simulated body fluid, and cytotoxicity assays showed they induced no significant death of human mesenchymal stem cells after 7 days. Calorimetric measurements were carried out under a wide range of alternating magnetic field amplitudes and frequencies, considering clinically relevant parameters, and some were made in viscous medium (agar) to mimic the implantation conditions. The experimental specific loss power was predictable with respect to the Linear Response Theory, and showed a maximal value of 767 ± 77 W gFe-1 (769 kHz, 23.9 kA m-1 in water). An interesting value of 166 ± 24 W gFe-1 was obtained under clinically relevant conditions (157 kHz, 23.9 kA m-1) for the heterostructures immobilized in agar. The good biocompatibility, bioactivity and heating ability suggest that these γ-Fe2O3@SiO2-CaO NPs are a promising biomaterial to be used as it is or included in a scaffold to heal bone defects resulting from bone tumor resection.

Loading with Biomolecules Modulates the Antioxidant Activity of Cerium-Doped Bioactive Glasses.

In order to identify new bioactive glasses (BGs) with optimal antioxidant properties, we carried out an evaluation of a series of cerium-doped BGs [Ce-BGs─H, K, and mesoporous bioactive glasses (MBGs)] loaded with different biomolecules, namely, gallic acid, polyphenols (POLY), and anthocyanins. Quantification of loading at variable times highlighted POLY on MBGs as the system with the highest loading. The ability to dismutate hydrogen peroxide (catalase-like activity) of the BGs evaluated is strongly correlated with cerium doping, while it is marginally decreased compared to the parent BG upon loading with biomolecules. Conversely, unloaded Ce-BGs show only a marginal ability to dismutate the superoxide anion (SOD)-like activity, while upon loading with biomolecules, POLY in particular, the SOD-like activity is greatly enhanced for these materials. Doping with cerium and loading with biomolecules give complementary antioxidant properties to the BGs investigated; combined with the persistent bioactivity, this makes these materials prime candidates for upcoming studies on biological systems.

Superparamagnetic and highly bioactive SPIONS/bioactive glass nanocomposite and its potential application in magnetic hyperthermia.

Magnetic bioactive glass-ceramics are biomaterials applied for magnetic hyperthermia in bone cancer treatment, thereby treating the bone tumor besides regenerating the damaged bone. However, combining high bioactivity and high saturation magnetization remains a challenge since the thermal treatment step employed to grow magnetic phases is also related to loss of bioactivity. Here, we propose a new nanocomposite made of superparamagnetic iron oxide nanoparticles (SPIONs) dispersed in a sol-gel-derived bioactive glass matrix, which does not need any thermal treatment for crystallization of magnetic phases. The scanning and transmission electron microscopies, X-ray diffraction, and dynamic light scattering results confirm that the SPIONs are actually embedded in a nanosized glass matrix, thus forming a nanocomposite. Magnetic and calorimetric characterizations evidence their proper behavior for hyperthermia applications, besides evidencing inter-magnetic nanoparticle interactions within the nanocomposite. Bioactivity and in vitro characterizations show that such nanocomposites exhibit apatite-forming properties similar to the highly bioactive parent glass, besides being osteoinductive. This methodology is a new alternative to produce magnetic bioactive materials to which the magnetic properties only rely on the quality of the SPIONs used in the synthesis. Thereby, these nanocomposites can be recognized as a new class of bioactive materials for applications in bone cancer treatment by hyperthermia.

Newly crosslinked chitosan- and chitosan-pectin-based hydrogels with high antioxidant and potential anticancer activity.

Monoaldehydes, due to natural origin and therapeutic activity, have attracted great attention for their ability to crosslink chitosan hydrogels for biomedical applications. However, most studies have focused on single-component hydrogels. In this work, chitosan-based hydrogels, crosslinked for the first time with 2,3,4-trihydroxybenzaldehyde (THBA), were modified with pectin (PC), bioactive glass (BG), and rosmarinic acid (RA). All of these were not only involved in the crosslinking, but also modulated properties or imparted completely new ones. THBA functioned as a crosslinker, resulting in improved mechanical properties, high swelling capacity and delayed degradation and also imparted high antioxidant activity and antiproliferative effect on cancer cells without cytotoxicity for normal cells. Hydrogels containing PC showed enhanced mechanical strength, while the combination with BG gave improved stability in PBS. All hydrogels modified with BG exhibited the ability to mineralise in SBF. The addition of RA enhanced antioxidant and anticancer activities and promoting the mineralisation process.

Odontogenesis by Endocytosis of Peptide Embedding Bioactive Glass Composite.

Limited therapeutic options are available for treating deep caries. Those materials with potential of a dual effect to remineralize hard tissue and regenerate defective dentin tissues could be used as a new strategy for deep caries treatment. However, the application of the single component remains a challenge mainly because they lack calcium and phosphorus, are easily degraded, and are difficult to retain in the intricate body fluid environment. Considering the abundant source of calcium and phosphorus as well as the delivery performance of mesoporous bioactive glass (MBG), an amelogenin-derived peptide (QP5), which has a significant role in hard tissue remineralization, was loaded to fabricate a novel composite. After the synthesis of highly ordered MBG using a sol-gel method, the QP5 peptide was loaded increasingly by its extensive porous structure and enhanced electrostatic absorption. When used in an acidic environment, the MBG/QP5 composite presented pH-responsiveness, releasing therapeutic ions and functional peptides in a sequential cascade, and eventually adjusted the pH to a neutral state. The composite was internalized by dental pulp cells through a clathrin-mediated pathway and influenced by cell membrane lipid raft regulation. It could be also transported through the macro-pinocytotic pathway. Compared to the single treatment of peptide QP5 in 48 h, the composite facilitated a higher level of retention of the intracellular peptides. The composite further promoted migration and odontogenesis of dental pulp cells, including the improved activity of alkaline phosphatase, increased formation of mineralized nodules, and upregulated expression of mineralization-related genes compared to using MBG or QP5 alone. The composite further induced the dentin-like layer in a rat pulp capping model. The results suggested that this intelligent material with pH-responsiveness provides a promising alternative treatment method for biomimetic restoration of deep caries.

Thermoluminescence dosimetric attributes of Yb3+ -doped BaO-ZnO-LiF-B2 O3 glass material after Er3+ co-doping.

Motivated by our previous study on Sm3+ ions as thermoluminescence (TL) sensitizers to the BaO-ZnO-LiF-B2 O3 -Yb2 O3 glass system, in the current study we examined the effect of Er3+ ion co-doping on the TL characteristics of this glass system. The 4f-4f electronic transitions of the Er3+ and Yb3+ ions were confirmed via the optical absorption spectrum. Notably, the use of Yb3+ -Er3+ ions failed to improve the TL intensity, sensitivity, and trap density. However, they enabled the glass system to function as an activator-quencher system. The linearity range and effective atomic number remained unaffected after co-doping. In addition, the problem of anomalous fading caused a remnant signal of just 58% after a week of storage of the Yb3+ monodoped glass. This was resolved by the optimum co-doping of Er3+ ions to achieve an 89% signal. The co-doping of Er3+ ions to the BaO-ZnO-LiF-B2 O3 -Yb2 O3 glass system regulated its thermal stability and therefore supplemented its potential for radiation monitoring in food processing and retrospective dosimetry.

Solvothermally-derived nanoglass as a highly bioactive material.

A highly bioactive glass solvBG76 in a binary system 76SiO2-24CaO (wt%) was prepared following a solvothermal path of the synthesis. The facile synthesis, in terms of the steps and reagents needed, enabled the achievement of a mesoporous material. Many factors such as nano-size (<50 nm), different morphology (non-spherical), use of an unconventional network modifier (calcium hydroxide) during the synthesis, a structure free of crystalline impurities, and textural properties greatly enhanced the kinetic deposition process of hydroxyapatite (HA) when contacting with physiological fluids. The formation of a HA layer on the glass was analyzed by various techniques, namely XRD, IR-ATR, Raman, XPS, EDS analyses, SEM, and HR-TEM imaging. The results obtained were compared to the 45S5 glass tested as a reference biomaterial as well as 70S30C-a glass with similar size and composition to reported solvBG76 but obtained by the conventional sol-gel method. For the first time, superior apatite-mineralization ability in less than 1 h in a physiological-like buffer was achieved. This unique bioactivity is accompanied by biocompatibility and hemocompatibility, which was indicated by a set of various assays in human dermal fibroblasts and MC3T3 mouse osteoblast precursor cells, as well as hemolytic activity determination.

Recommendation of Single Time Point Leachables Testing for Lyophilized Biotechnology Products Stored in Rubber Stoppered Glass Vial Systems.

As a popular format of primary container closure systems, rubber stoppered glass vials are often used in storing and delivering lyophilized and liquid formulated therapeutic protein products. Assessing extractables and leachables from rubber stoppered glass vial systems is required to ensure drug product quality and patient safety. Lyophilized biopharmaceutical drug products are generally considered as less impacted by leachables during storage and transportation than the liquid formulated drug products. Single time point leachables testing for lyophilized biopharmaceutic drug products is recommended. The recommendation is based on our published comprehensive leachable data collected at multiple time points for five lyophilized drug products stored in different rubber stoppered glass vial systems with additional supporting comprehensive leachable data collected for nineteen liquid formulated drug products stored in different syringe and vial systems, which is statistically and scientifically sound. The leachable data evaluated herein were generated based on a holistic approach which ensured successful qualification of different vial systems as primary containers and delivery systems for various biotherapeutic products. The organic and elemental impurities of the leachable profiles of all the twenty-four drug product samples were below the limit of detection at all the time points. For lyophilized drug products, product surface interaction during storage time and shipping is unlikely. Timing of single time point leachables testing can be flexible. Performing leachables testing at one-year time point is recommended as it allows for enough time for chemicals to leach out from product contact surfaces into drug products and thus provides the earliest opportunity for mitigation of unpredicted leachables of concern, if any. However, testing at other stability time points can also be considered depending on the development strategy of the sponsor. Therefore, recommendation of single time point leachables testing for lyophilized drug products stored in rubber stopped glass vials at an appropriate time point is a scientifically sound approach.