Release Of Ca Ions Research Articles

Chondroitin Sulfate-Modified Hydroxyapatite for Caspase-1 Activated Induced Pyroptosis through Ca Overload/ER Stress/STING/IRF3 Pathway in Colorectal Cancer.

Immune checkpoint inhibitors, are the fourth most common therapeutic tool after surgery, chemotherapy, and radiotherapy for colorectal cancer (CRC). However, only a small proportion (≈5%) of CRC patients, those with "hot" (immuno-activated) tumors, benefit from the therapy. Pyroptosis, an innovative form of programmed cell death, is a potentially effective means to mediate a "cold" to "hot" transformation of the tumor microenvironment (TME). Calcium-releasing hydroxyapatite (HAP) nanoparticles (NPs) trigger calcium overload and pyroptosis in tumor cells. However, current limitations of these nanomedicines, such as poor tumor-targeting capabilities and insufficient calcium (Ca) ion release, limit their application. In this study, chondroitin sulfate (CS) is used to target tumors via binding to CD44 receptors and kaempferol (KAE) is used as a Ca homeostasis disruptor to construct CS-HAP@KAE NPs that function as pyroptosis inducers in CRC cells. CS-HAP@KAE NPs bind to the tumor cell membrane, HAP released Ca in response to the acidic environment of the TME, and kaempferol (KAE) enhances the influx of extracellular Ca, resulting in intracellular Ca overload and pyroptosis. This is associated with excessive endoplasmic reticulum stress triggered activation of the stimulator of interferon genes/interferon regulatory factor 3 pathway, ultimately transforming the TME from "cold" to "hot".

Enhancing the Physical, Antimicrobial, and Osteo/Odontogenic Properties of a Sol-Gel-Derived Tricalcium Silicate by Graphene Oxide for Vital Pulp Therapies.

This study developed a sol-gel tricalcium silicate/graphene oxide (TCS-GO) composite and examined its physicochemical properties, antimicrobial activity, and osteo/odontogenic effect on dental pulp stem cells. Tricalcium silicate was synthesized and combined with graphene oxide at three different concentrations, namely 0.02%, 0.04%, and 0.08% w/w, while tricalcium silicate and mineral trioxide aggregate served as controls. The setting time, compressive strength, pH, and calcium ion release of the composites were evaluated, as well as antimicrobial properties against Streptococcus mutans and Lactobacillus acidophilus. Additionally, the viability of dental pulp stem cells; apatite forming ability; and the gene expression of Alkaline phosphatase, Dentin sialophosphoprotein, and Runt-related transcription factor 2 were assessed. TCS-GO (0.08%) showed a significantly shorter setting time and higher compressive strength when compared to MTA (p < 0.05). Additionally, tricalcium silicate and TCS-GO groups showed a higher release of Ca ions than MTA, with no significant difference in pH values among the different groups. TCS-GO (0.08%) also demonstrated a significantly stronger antimicrobial effect against Lactobacillus acidophilus compared to MTA (p < 0.05). ALP expression was higher in TCS-GO (0.08%) than MTA on days 3 and 7, while DSPP expression was higher in TCS-GO (0.08%) than MTA on day 3 but reversed on day 7. There was no significant difference in RUNX2 expression between TCS-GO (0.08%) and MTA on days 3 and 7. The TCS-GO (0.08%) composite demonstrated superior physicochemical characteristics and antimicrobial properties compared to MTA. Moreover, the early upregulation of ALP and DSPP markers in TCS-GO (0.08%) indicates that it has the potential to promote and enhance the osteo/odontogenic differentiation of DPSCs.

Cu-doped 70S bioactive glass fibrous membranes produced using solution blow spinning (SBS)

3D fibrous membranes of undoped and Cu-doped 70S glass were developed, by solution blow spinning. The concentration of copper ions ranged from 1 to 4 % in mol. As-spun fibers were calcined/stabilized at 700 °C. The produced membranes' morphological and biological properties and the release of Ca and Cu ions were evaluated. Amorphous materials were obtained in pure and doped with 1 % Cu2+ 70S glass, while metallic copper was observed in 4 % Cu2+ doped glass. All samples have fibers with average diameter at the submicron scale, ranging from 700 to 850 nm. The amount of Cu ions influenced the degradation of the samples and the release of Cu and Ca ions in the Tris solution, the greater the amount of copper the more these ions were degraded and released in the solution. In vitro biological results, showed that adding copper favored the biomineralization process. No toxicity was observed in the MMT test for all samples. Alamar Blue method showed cell viability for fibroblasts greater than 90 % for all samples and for osteoblasts greater than 70 % for the BG-70S.2Cu sample. The developed fibrous membranes presented antimicrobial characteristics against Staphylococcus aureus and Candida albicans.

Bioinspired core-shell nanofiber drug-delivery system modulates osteogenic and osteoclast activity for bone tissue regeneration

Osteogenic-osteoclast coupling processes play a crucial role in bone regeneration. Recently, strategies that focus on multi-functionalized implant surfaces to enhance the healing of bone defects through the synergistic regulation of osteogenesis and osteoclastogenesis is still a challenging task in the field of bone tissue engineering. The aim of this study was to create a dual-drug release-based core-shell nanofibers with the intent of achieving a time-controlled release to facilitate bone regeneration. We fabricated core-shell P/PCL nanofibers using coaxial electrospinning, where alendronate (ALN) was incorporated into the core layer and hydroxyapatite (HA) into shell. The surface of the nanofiber construct was further modified with mussel-derived polydopamine (PDA) to induce hydrophilicity and enhance cell interactions. Surface characterizations confirmed the successful synthesis of PDA@PHA/PCL-ALN nanofibers endowed with excellent mechanical strength (20.02 ± 0.13 MPa) and hydrophilicity (22.56°), as well as the sustained sequential release of ALN and Ca ions. In vitro experiments demonstrated that PDA-functionalized core-shell PHA/PCL-ALN scaffolds possessed excellent cytocompatibility, enhanced cell adhesion and proliferation, alkaline phosphatase activity and osteogenesis-related genes. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity and osteoclastogenesis-related gene expression. After 12-week of implantation, it was observed that PDA@PHA/PCL-ALN nanofiber scaffolds, in a rat cranial defect model, significantly promoted bone repair and regeneration. Microcomputed tomography, histological examination, and immunohistochemical analysis collectively demonstrated that the PDA-functionalized core-shell PHA/PCL-ALN scaffolds exhibited exceptional osteogenesis-inducing and osteoclastogenesis-inhibiting effects. Finally, it may be concluded from our results that the bio-inspired surface-functionalized multifunctional, biomimetic and controlled release core-shell nanofiber provides a promising strategy to facilitate bone healing.

Unlocking the potential of iron-containing mesoporous bioactive glasses: Orchestrating osteogenic differentiation in bone marrow mesenchymal stem cells and osteoblasts

Iron (Fe) is a crucial element in the human body, playing a significant role in bone metabolism. The release of Fe ions at bone defect sites can promote bone regeneration. In this study, we synthesized Fe-containing mesoporous bioactive glasses (Fe-MBGs) in SiO2-CaO-Fe2O3 composition using a sol-gel method. Regardless of the amount of incorporated Fe2O3 (up to 5 mol%), the Fe-MBGs maintained a mesoporous structure, and the inclusion of Fe2O3 did not alter their amorphous characteristics. However, the presence of Fe2O3 led to a reduction in both pore volume and specific surface area of Fe-MBGs. Notably, Fe-MBGs demonstrated degradability in physiological fluids and could sustain release of Si, Fe, and Ca ions. Higher concentrations of incorporated Fe2O3 were found to reduce the degradation of Fe-MBGs. All Fe-MBGs exhibited favorable bioactivity, as evidenced by the rapid formation of hydroxyapatite when exposed to simulated body fluid. Fe-MBGs also demonstrated concentration-dependent effects on BMSCs and Saos-2 cells. Extracts of Fe-MBGs at 0.1 and 1 mg/mL exhibited non-cytotoxicity and promoted cell proliferation. Additionally, extracts of Fe-MBGs at 1 mg/mL significantly enhanced the alkaline phosphatase activity of BMSCs and Saos-2 cells, along with an upregulation of the expression of osteogenesis-related genes. These findings unlock the significant potential of Fe-MBGs as functional biomaterials for bone regeneration applications. The controlled release of Fe ions from these mesoporous bioactive glasses orchestrates osteogenic differentiation in bone marrow mesenchymal stem cells and osteoblasts.

Versatile Bioactive Glass/Zeolitic Imidazolate Framework-8-Based Skin Scaffolds toward High-Performance Wound Healing.

Designing a novel biomaterial for wound healing is based on biocompatibility and excellent mechanical strength. In this study, bioactive glass (BG) and zeolitic imidazolate framework-8 (ZIF-8) have been incorporated into poly(ε-caprolactone)/poly(vinyl alcohol) (PCL/PVA) composite skin scaffolds via microfluidic electrospinning. Interestingly, the addition of ZIF-8 further strengthens the BG stability and demonstrates better antibacterial effects. Utilizing the slow release of Zn, Ca, and Si ions, it also significantly promotes growth factor expression and skin regeneration. In addition, it is further demonstrated by in vitro and in vivo studies that the prepared composite skin scaffolds possess excellent biocompatibility, antibacterial capabilities, and mechanical properties. The prepared BG/ZIF-8-loaded scaffold possesses high tensile strength (26 MPa) and excellent antibacterial properties (achieves 89.64 and 78.8% inhibition of E. coli and S. aureus, respectively), and cell viability increased by 51.2%. More importantly, the wound shrinkage of the BG/ZIF-8-loaded scaffold is better than that of an unloaded scaffold, and the shrinkage rates of PCL/PVA@BG/ZIF-8(1 wt %) group is 95% with 2.2 mm granulation growth thickness within 12 days. Thus, the composite skin scaffold loaded with BG/ZIF-8 prepared by microfluidic electrospinning provides a new perspective for accelerating wound healing and is a potential novel therapeutic strategy for efficient wound healing.

Synthesis of a Calcium Silicate Cement Containing a Calcinated Strontium Silicate Phase.

The positive effects of strontium on dental and skeletal remineralization have been confirmed in the literature. This study aimed to assess the properties of a calcium silicate cement (CSC) containing a sintered strontium silicate phase. The calcium silicate and strontium silicate phases were synthesized by the sol-gel technique. Strontium silicate powder in 0 (CSC), 10 (CSC/10Sr), 20 (CSC/20Sr), and 30 (CSC/30Sr) weight percentages was mixed with calcium silicate powder. Calcium chloride was used in the liquid phase. X-ray diffraction (XRD) of specimens was conducted before and after hydration. The setting time and compressive strength were assessed at 1 and 7 days after setting. The set discs of the aforementioned groups were immersed in the simulated body fluid (SBF) for 1 and 7 days. The ion release profile was evaluated by inductively coupled plasma-optical emission spectrometry (ICP-OES). Biomineralization on the specimen surface was evaluated by scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS). Data were analyzed by the Kolmogorov-Smirnov test, one-way and mixed ANOVA, Levene's test, and LSD post hoc test (P < 0.05). Except for an increasement in the peak intensity of hydrated specimens, XRD revealed no other difference in the crystalline phases of hydrated and nonhydrated specimens. The compressive strength was not significantly different at 1 and 7 days in any group (P > 0.05). The setting time significantly decreased by an increase in percentage of strontium (P < 0.05). Release of Ca and Si ions significantly decreased by an increase in percentage of strontium (P < 0.05). SEM/EDS showed the formation of calcium phosphate deposits at 1 and 7 days. Incorporation of 10-30 wt% sintered strontium silicate phase as premixed in CSC can significantly decrease the setting time without compromising the compressive strength or biomineralization process of the cement.

Metal-organic complex coating for enhanced corrosion control and biocompatibility on biodegradable magnesium alloy for orthopaedic implants.

Magnesium alloy is currently regarded as the most favourable biodegradable metal; however, obstacles remain to be overcome in terms of managing its corrosion and ensuring its biocompatibility. In this study, a metal-organic complex comprising Ca ions incorporated in tannic acid (TA) was prepared and used to coat magnesium alloy by chemical conversion and dipping processes, followed by modification with stearic acid (SA). This metal-organic complex coating was demonstrated to be homogeneous and compact, and it significantly improved the electrochemical corrosion resistance and long-term degradation behaviour of the coated samples. Consequently, the well-controlled release of Mg and Ca ions, as well as the osteo-compatible TA and SA molecules, promoted the proliferation of osteoblast cells. This metal-organic complex coating offers a promising modifying strategy for magnesium-based orthopaedic implants.

Temperature-responsive bioactive glass/polymer hybrids allow for tailoring of ion release.

Intelligent biomaterials react to their surrounding conditions, and hybrid materials are acknowledged for their remarkable customizability, achieved through the meticulous control of nanoscale interactions between organic and inorganic phases. Bioactive glasses (BG) are used clinically to regenerate bone due to their degradability, ion release, and capacity to stimulate the formation of new body tissue. In our study, we developed a core-shell hybrid system using sol-gel derived BG nano particles as the core and poly (N-isopropyl acrylamide) (PNIPAM) as the shell. This approach aims to combine the therapeutic ion release of BG with the temperature-responsive properties of PNIPAM. Our size analysis by dynamic light scattering at varying temperatures shows the formation of BG aggregates driven by the coil-to-globule transition of PNIPAM on the BG surface. This transition also affected the ion release from the core-shell system through an increase in ion transport through the porous hybrid network. Our study therefore illustrates the ability to adjust the dissolution properties of the core-shell system via surrounding temperature and, thus, control the release of Ca ions from the BG.

Remediation of As-contaminated soil by utilizing steel slag-based passivators with different Fe/Ca ratios: As bioavailability and passivation characterization

Iron (Fe) and calcium (Ca)-based solid wastes are widely applied to remediate heavy metals-contaminated soil, whereas their passivation efficiencies and mechanisms for arsenic (As) remain largely unknown. Herein, we employed different steel slags (SS) composited with FeSO4 (Fe/Ca molar ratios: 0.45, 1.03, and 10.66) as novel passivators to investigate the passivation characteristics of As. Batch experimental results indicated that the optimal As passivation efficiency was achieved for the high-Fe (Fe/Ca = 10.66) amendment, in which the available As content was reduced significantly by 90.7% from 7.02 to 0.65 mg/kg, and leached As concentrations were below the regulatory limits of “Standards for drinking water quality” (GB5749-2022, China). The decreased As bioavailability in the high-Fe amendment was attributed to the effective conversion of labile As fractions (F1 and F2) to the most stable As fraction (F5). Synergistic effects of SS and FeSO4 facilitated the formation of amorphous Fe (III) (oxyhydr)oxides and the release of Ca ions, which enhanced the chemisorption of As. The As could be captured by poorly crystalline FeOOH and amorphous Fe (III) (oxyhydr)oxides, and Fe–As complexes and precipitates (FeAsO4) were generated with the internal diffusion of As, which were of great effect on the long-term As passivation. Although Ca–As coprecipitates were produced, the contribution of As passivation by free Ca species was relatively limited compared to Fe species. This work provides theoretical guidance for the application of iron-based solid wastes (e.g., SS) in As-contaminated soil remediation.

Electroactive Hydrogels with Photothermal/Photodynamic Effects for Effective Wound Healing Assisted by Polydopamine-Modified Graphene Oxide.

Antibacterial hydrogel wound dressings have attracted considerable attention in recent years. However, bacterial infections can occur at any point during the wound-healing process. There is a demand for hydrogels that possess on-demand antibacterial and excellent wound repair properties. Herein, we report a near-infrared (NIR)-light-responsive indocyanine green (ICG)-loaded polydopamine (PDA)-mediated graphene oxide (PGO) and amorphous calcium phosphate (CaP)-incorporated poly(vinyl alcohol) (PVA) hydrogel using a mussel-inspired approach. PGO was reduced by PDA, which endowed the hydrogel with electroactivity and provided abundant sites for loading ICG. Amorphous CaP was formed in situ in the PVA hydrogel to enhance its mechanical properties and biocompatibility. Taking advantage of the high photothermal and photodynamic efficiency of ICG-PGO, the ICG-PGO-CaP-PVA hydrogel exhibited fascinating on-demand antibacterial activity through NIR light irradiation. Moreover, the thermally induced gel-sol conversion of PVA accelerated the release of Ca ions and allowed the hydrogel to adapt to irregular wounds. Meanwhile, PGO endows the hydrogel with conductivity and cell affinity, which facilitate endogenous electrical signal transfer to control cell behavior. In vitro and in vivo studies demonstrated that the ICG-PGO-CaP-PVA hydrogel exhibited a strong tissue repair activity under NIR light irradiation. This mussel-inspired strategy offers a novel way to design hydrogel dressings for wound healing.

The Addition of Copper Nanoparticles to Mineral Trioxide Aggregate for Improving the Physical and Antibacterial Properties

The physical and antibacterial properties of mineral trioxide aggregate (MTA) have been improved by adding copper nanoparticles (CuNP). The CuNP colloid was synthesized by reacting CuCl2·2H2O and NaBH4 as the reducing agent using C6H8O6 as the capping agent. The Cu(II) concentration was varied by 3.0, 6.0, and 9.0 mM to produce CuNP-3, CuNP-6, and CuNP-9 colloids, respectively. The CuNP colloids were characterized with a UV-Vis spectrophotometer and TEM. MTA was hydrated with CuNP at a mass-to-volume ratio of 2:1 to produce Cu-MTA-3, Cu-MTA-6, and Cu-MTA-9, respectively. All products were characterized with XRD and SEM-EDX. The compressive strength, pH, Ca ion release, and solubility were measured, and antibacterial activity was tested. The results showed a spherical shape of the synthesized CuNP with a particle size of ~28.08 nm. Adding CuNP-9 to hydrated MTA increased the compressive strength, pH, Ca ion release, and solubility, with the value of 4.78±0.38 MPa; 9.01±0.03; 1718±63 ppm, and 22.48±0.37%, respectively. The highest antibacterial activity occurred for Cu-MTA-9, with an inhibition zone of 10.15±0.47 mm against S. aureus and 11.93±1.16 mm against P. aeruginosa. The findings show a potential application of the product for endodontic materials containing antibacterial agents.

Multifunctional chitosan/alginate hydrogel incorporated with bioactive glass nanocomposites enabling photothermal and nitric oxide release activities for bacteria-infected wound healing

It is highly desirable to develop novel multifunctional wound dressing materials capable of delivering active molecules capable of resolving bacterial infections and replenishment of appropriate growth factors for bacteria-infected wound healing. Polysaccharides have numerous biomedical benefits and have been widely used to construct biomaterial scaffolds. Herein, multifunctional chitosan/alginate hydrogel decorated with β-cyclodextrin (β-CD) modified polydopamine (PDA)-bioactive glass (BG) nanoparticles (NPs) integrating photothermal performance and nitric-oxide release activities for the treatment of bacterially infected wounds is presented. As the NO precursor N,N′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine (BNN6) encapsulated into the hydrophobic cavity of β-CD on the PDA-coated BG NPs, the resultant NO@CD-PDA/BG NPs, are imparted with the feature of NIR triggered NO release and desired PTT/NO synergetic antibacterial effects. Furthermore, the release of NO, Ca, and Si ions from the NO@CD-PDA/BG NPs, has the benefit of regulating inflammation, promoting fibroblast proliferation, and stimulating angiogenesis. Besides, the chitosan/alginate hydrogel scaffolds provided a suitable microenvironment to accelerate wound healing. By applying the multifunctional chitosan/alginate nanocomposite hydrogel to S. aureus-infected full-thickness skin defect mouse model, the authors demonstrated that chitosan/alginate nanocomposite hydrogel has multiple functions in preventing bacterial infections, accelerating angiogenesis and wound regeneration, indicating promising application in wound healing.

Mussel-inspired multifunctional surface through promoting osteogenesis and inhibiting osteoclastogenesis to facilitate bone regeneration

Osteogenesis and osteoclastogenesis are closely associated during the bone regeneration process. The development of multifunctional bone repair scaffolds with dual therapeutic actions (pro-osteogenesis and anti-osteoclastogenesis) is still a challenging task for bone tissue engineering applications. Herein, through a facile surface coating process, mussel-inspired polydopamine (PDA) is adhered to the surface of a biocompatible porous scaffold followed by the immobilization of a small-molecule activator (LYN-1604 (LYN)) and the subsequent in situ coprecipitation of hydroxyapatite (HA) nanocrystals. PDA, acting as an intermediate bridge, can provide strong LYN immobilization and biomineralization ability, while LYN targets osteoclast precursor cells to inhibit osteoclastic differentiation and functional activity, which endows LYN/HA-coated hybrid scaffolds with robust anti-osteoclastogenesis ability. Due to the synergistic effects of the LYN and HA components, the obtained three-dimensional hybrid scaffolds exhibited the dual effects of osteoclastic inhibition and osteogenic stimulation, thereby promoting bone tissue repair. Systematic characterization experiments confirmed the successful fabrication of LYN/HA-coated hybrid scaffolds, which exhibited an interconnected porous structure with nanoroughened surface topography, favorable hydrophilicity, and improved mechanical properties, as well as the sustained sequential release of LYN and Ca ions. In vitro experiments demonstrated that LYN/HA-coated hybrid scaffolds possessed satisfactory cytocompatibility, effectively promoting cell adhesion, spreading, proliferation, alkaline phosphatase activity, matrix mineralization, and osteogenesis-related gene and protein secretion, as well as stimulating angiogenic differentiation of endothelial cells. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity, F-actin ring staining, and osteoclastogenesis-related gene and protein secretion. More importantly, in a rat calvarial defect model, the newly developed hybrid scaffolds significantly promoted bone repair and regeneration. Microcomputed tomography, histological, and immunohistochemical analyses all revealed that the LYN/HA-coated hybrid scaffolds possessed not only reliable biosafety but also excellent osteogenesis-inducing and osteoclastogenesis-inhibiting effects, resulting in faster and higher-quality bone tissue regeneration. Taken together, this study offers a powerful and promising strategy to construct multifunctional nanocomposite scaffolds by promoting osteo/angiogenesis and suppressing osteoclastogenesis to accelerate bone regeneration.

Novel rechargeable calcium fluoride dental nanocomposites

ObjectivesComposite restorations with calcium fluoride nanoparticles (nCaF2) can remineralize tooth structure through F and Ca ion release. However, the persistence of ion release is limited. The objectives for this study were to achieve long-term remineralization by developing a rechargeable nCaF2 nanocomposite and investigating the F and Ca recharge and re-release capabilities. MethodsThree nCaF2 nanocomposites were formulated: (1) BT-nCaF2:Bisphenol A glycidyl dimethacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA); (2) PE-nCaF2:Pyromellitic glycerol dimethacrylate (PMGDM) and ethoxylated bisphenol A dimethacrylate (EBPADMA); (3) BTM-nCaF2:BisGMA, TEGDMA, and Bis[2-(methacryloyloxy)ethyl] phosphate (Bis-MEP). All formulations contained 15% nCaF2 and 55% glass particles. Initial flexural strength and elastic modulus, F and Ca ion release, recharge and re-release were tested and compared to three commercial fluoride-containing materials. ResultsBT and BTM nCaF2 composites were 3–4 times stronger and had elastic modulus 2 times that of resin-modified glass ionomer controls. PE-nCaF2 had comparable strength to RMGIs. All nCaF2 composites had significant F and Ca ion release and ion rechargeability. In F and Ca recharging cycles, PE-nCaF2 had the highest ion recharging capability among nCaF2 groups, followed by BT-nCaF2 and BTM-nCaF2 (p < 0.05). For all recharge cycles, ion release maintained similar levels, demonstrating long-term ion release was possible. Furthermore, after the final recharge cycle, nCaF2 nanocomposites provided continuous ion release for 42 days without further recharge. SignificanceNovel nCaF2 rechargeable nanocomposites exhibited significant F and Ca ion release over multiple recharge cycles, demonstrating continuous long-term ion release. These nanocomposites are promising restorations with lasting remineralization potential.

Silver- and/or titanium-doped β-tricalcium phosphate bioceramic with antibacterial activity against Staphylococcus aureus

Ag- and/or Ti-doped apatitic-tricalcium phosphate powders were synthesized by wet chemical precipitation method. Regardless of the element composition, calcination of the Ag- and/or Ti-doped apatitic tricalcium phosphate powders at 900 °C gave phase-pure β-tricalcium phosphate. Cumulative release of Ca(II) and Ag(I) ions in TRIS-HCl buffer solution was determined. Increase of the solubility of the β-tricalcium phosphate was observed with the addition of Ti. Furthermore, prolonged (up to 28 days) release of the Ag(I) ions from the Ag-doped and the Ag- and Ti-co-doped β-tricalcium phosphate was observed. Minimum inhibitory concentration and antibacterial activity of the Ag- and/or Ti-doped β-tricalcium phosphate powders against Gram-positive Staphylococcus aureus was determined. It was observed that the addition of both, Ti and Ag, confers antibacterial properties of the β-tricalcium phosphate against Staphylococcus aureus.

Bioinspired Redwood-Like Scaffolds Coordinated by In Situ-Generated Silica-Containing Hybrid Nanocoatings Promote Angiogenesis and Osteogenesis both In Vitro and In Vivo.

Inspired by natural redwood and bone, a biomimetic strategy is presented to develop a highly bioactive redwood-like nanocomposite via radial freeze casting of biocompatible hydrogels followed by the in situ coprecipitation of a Si-containing CaP hybrid nanocoating (SCPN). The engineered material displays radially aligned macrochannels and a porous network structure similar to those of natural redwood. In addition to acting as a mechanical reinforcement, introducing SCPNs into the weak redwood-like scaffold yields not only a nanoroughened surface topography, a low swelling ratio, retarded enzymatic degradation, and enhanced protein absorption abilities but also the sustained sequential release of Si and Ca ions, thereby providing essential biophysical and biochemical cues for effective bone regeneration. Benefiting from the redwood-like structures and bioactive SCPNs, the biomimetic materials create a favorable microenvironment for promoting the initial adhesion, spreading, proliferation, and migration of bone marrow-derived mesenchymal stem cells and human umbilical vein endothelial cells. Furthermore, the in vitro and in vivo data showed that the biocompatible redwood-like scaffold with precipitated SCPN can synergistically promote osteogenesis and angiogenesis in their aligned direction. Collectively, this work presents a novel bioinspired redwood-like material with multifunctional properties that provides new insight into bone defect repair.

Tracing the toxic ions of an endodontic tricalcium silicate-based sealer in local tissues and body organs

BackgroundThis study aimed to track the toxic ions released by MTA Fillapex, BioRoot RCS, and an experimental tricalcium silicate-based sealer (CEO) into local and distant tissues as well as to investigate their potential adverse effects. In addition, the chemical constituents of the sealers were also evaluated. The main components of the dry powders, pastes, and mixed sealers were characterized. Material and methodsDry powder and sealer discs were each set for 72 h and their main components were characterized by energy dispersive X-ray spectroscopy. Polyethylene tubes filled with sealers were used to measure silicon and calcium ions. Polyethylene tubes filled with sealers or empty tubes were implanted into the dorsal connective tissue of Wistar rats. On days 7, 15, 30, and 45, the animals were euthanized and their brains, livers, kidneys, and subcutaneous tissues were removed and processed to determine the concentrations of chromium, cobalt, copper, lead, iron, magnesium and nickel using an inductively coupled plasma optical emission spectrometer. ResultsThe main compounds in all sealers were carbon, oxygen, silicon, and calcium. MTA Fillapex release more Si while highest levels of Si were found in presence of BioRoot. The release of Si and Ca ions promoted by MTA Fillapex raise by time. No traces of cobalt, chromium, or magnesium were detected in any tissue. Irrespective of the sealer, no traces of copper and lead were found in the subcutaneous tissue; however, they were observed in the organs. The highest concentration of iron was identified in the liver. All sealers exhibited similar nickel traces in the brain, kidney, and liver except for MTA Fillapex, which demonstrated levels higher than CEO in the subcutaneous tissue on day 7. Tracing nickel ions over time revealed that lowest concentrations were found in subcutaneous tissue. ConclusionTaken together, our data demonstrate that CEOs have chemical compositions similar to those of other commercial sealers. Furthermore, none of them exhibited a threat to systemic health. Moreover, the minimal amounts of iron and nickel detected were not related to the sealers.

Investigation into Effect of Natural Shellac on the Bonding Strength of Magnesium Substituted Hydroxyapatite Coatings Developed on Ti6Al4V Substrates

The bioactive and biocompatible properties of hydroxyapatite (HA) promote the osseointegration process. To enhance other bio-functions of HA such as improving the antibacterial property of the implant, increasing the rate of cell proliferation, or improving tissue generation capability, HA is substituted with many elements such as Zn, Cl, Ba, Fe, Cu, Ag, Sr, F, Na, etc. This study reports development of Magnesium substituted HA (Mg-HA) coatings on Ti6Al4V substrates using the dip coating technique. To improve the adhesion and stability of the coating, an intermediate layer of shellac was applied between the coating and Ti6Al4V substrate. The dip coating process parameters were optimized using the Taguchi technique and it was found that dipping time of 35 s and 13% w/w of shellac concentration provided the maximum bonding strength of 12.5 MPa. The biocompatibility, dissolution, and corrosion study of the developed coating using the optimal parameters obtained were carried out in this study. An improvement in cell growth and cell proliferation was observed in the extract medium prepared from coated substrates. Release of Ca, P and Mg ions from the surface of the coated substrate into the simulated body fluid (SBF) was found to be almost constant which shows the stability of the thin film coating formed. The Mg-HA coated substrate also exhibited better corrosion resistance than the uncoated substrate.

Antioxidant cerium ions-containing mesoporous bioactive glass ultrasmall nanoparticles: Structural, physico-chemical, catalase-mimic and biological properties

The multifunctional biological properties of Ce ions including antioxidant, anti-inflammatory, antibacterial and anti-cancer effects are very encouraging for development of Ce-containing biomaterials with therapeutic properties. Herein, novel Ce3+/Ce4+ ions containing mesoporous bioactive glass ultrasmall nanoparticles (Ce-BGn) were prepared by a facile one-pot ultrasound-assisted sol-gel method. Interestingly, Ce2O3 incorporation exerted a significant influence on the particle size and textural properties of mesoporous BGn (SiO2 – CaO binary glass system). Ce-BGn exhibited ultrasmall nanoparticle size (< 30 nm), mesoporous texture (pore size up to 2.82 nm and pore volume up to 0.191 cm3/g) and large specific surface area ca. 132.9 m2/g. Notably, in situ formation of CeO2 nanospheres (3–6 nm) was detected at the surface and in the amorphous glass matrix of mesoporous Ce-BGn. Importantly, X-ray photoelectron spectroscopy (XPS) revealed the presence of 72.57 % Ce3+ and 27.43 % Ce4+ at the surface of mesoporous Ce-BGn with Ce3+/Ce4+ ratio = 2.66. Furthermore, mesoporous Ce-BGn exhibited high catalase-mimic activity and showed sustained release of Ce (2.5–32 ppm), Ca (85–327 ppm) and Si (54–200 ppm) ions within 4 weeks along with excellent bone-like hydroxyapatite formation. Finally, the in vitro biological behavior of mesoporous Ce-BGn in cell cultures of human skin fibroblasts (HSF) revealed that mesoporous Ce-BGn (with concentrations up to 300 μg/mL) possess good cyto-biocompatibility. Taken together, novel ultrasmall mesoporous Ce-BGn showed remarkable catalase-mimic activity via surface containing Ce3+/Ce4+ ions which can scavenge ROS (Ce3+↔ Ce4+) and decompose H2O2 molecules into H2O and O2. In addition to that, Ce-BGn demonstrated sustained release of bioactive ions (Ce, Ca and Si), excellent bone-like hydroxyapatite formation and good cyto-biocompatibility.