Bioactive Metal Research Articles

Ga-containing Ti alloy with improved osseointegration for bone regeneration: In vitro and in vivo studies

Ti and Ti alloys are widely used implant materials in clinical orthopedics because of their excellent mechanical properties, wear resistance, and biocompatibility. However, the therapeutic effect of Ti alloys is limited by their poor osseointegration. Thus, this study aimed to improve the poor osteointegration of Ti by fabricating Ti alloys containing different amounts of Ga. The properties, including element distribution, hardness, and calcium salt deposition of the Ti–Ga alloys were evaluated. Results showed that Ga, as a bioactive metal, promoted apatite formation. The osteogenic performance of the Ti–Ga alloys was evaluated in vitro and in vivo using rat bone marrow mesenchymal stem cells (BMSCs) and a rat intramedullary nail model, respectively. Biological results demonstrated that the Ti–Ga alloys provided suitable conditions for cell adhesion and spreading, promoted the osteogenic differentiation of BMSCs, and enhanced osseointegration in vivo better than pure Ti. Transcriptomic results further indicated that Ga enhanced osseointegration by downregulating gremlin expression. This study introduced Ti–Ga alloys as promising implant materials with better osseointegration than pure Ti and elucidated the possible mechanism by which Ga promotes osteogenesis.

Beyond Antiresorptive Activity: Risedronate-Based Coordination Complexes To Potentially Treat Osteolytic Metastases.

Coordination of clinically employed bisphosphonate, risedronate (RISE), to bioactive metals, Ca2+, Mg2+, and Zn2+, allowed the formation of bisphosphonate-based coordination complexes (BPCCs). Three RISE-based BPCCs, RISE-Ca, RISE-Mg, and RISE-Zn, were produced, and their structures were elucidated by single crystal X-ray diffraction. Interestingly, the addition of an auxiliary ligand, etidronic acid (HEDP), resulted in the recrystallized protonated form of the ligand, H-RISE. The pH-dependent structural stability of the RISE-based BPCCs was measured by means of dissolution profiles under neutral and acidic simulated physiological conditions (PBS and FaSSGF, respectively). In comparison to RISE (Actonel), the complexes showed a lower equilibrium solubility (∼70-85% in 18-24 h) in PBS, while a higher equilibrium solubility (∼100% in 3 h) in acidic media. The results point to the capacity to release this BP in a pH-dependent manner from the RISE-based BPCCs. Subsequently, the particle size of RISE-Ca was reduced, from 300 μm to ∼350 d.nm, employing the phase inversion temperature (PIT)-nanoemulsion method, resulting in nano-Ca@RISE. Aggregation measurements of nano-Ca@RISE in 1% fetal bovine serum (FBS):H2O was monitored after 24, 48, and 72 h to study the particle size longevity in physiological media, showing that the suspended material has the potential to maintain its particle size over time. Furthermore, binding assays were performed to determine the potential binding of nano-Ca@RISE to the bone, where results show higher binding (∼1.7×) for the material to hydroxyapatite (HA, 30%) when compared to RISE (17%) in 1 d. The cytotoxicity effects of nano-Ca@RISE were compared to those of RISE against the human breast cancer MDA-MB-231 and normal osteoblast-like hFOB 1.19 cell lines by dose-response curves and relative cell viability assays in an in vitro setting. The results demonstrate that nano-Ca@RISE significantly decreases the viability of MDA-MB-231 with high specificity, at concentrations ∼2-3× lower than the ones reported employing other third-generation BPs. This is supported by the fact that when normal osteoblast cells (hFOB 1.19), which are part of the tissue microenvironment at metastatic sites, were treated with nano-Ca@RISE no significant decrease in viability was observed. This study expands on the therapeutic potential of RISE beyond its antiresorptive activity through the design of BPCCs, specifically nano-Ca@RISE, that bind to the bone and degrade in a pH-dependent manner under acidic conditions.

Research Progress on Bioactive Metal Complexes against ER-Positive Advanced Breast Cancer.

Breast cancer is the most prevalent cancer in women and represents a serious disease that is harmful to life and health. In 1977, with the approval of tamoxifen, endocrine therapy has become the main clinical treatment for ER-positive (ER+) breast cancer. Although patients initially respond well to endocrine therapies, drug resistance often emerges and side effects can be challenging. To overcome drug resistance, the exploration for new drugs is a priority. Metal complexes have demonstrated significant antitumor activities, and platinum complexes are widely used in the clinic against various cancers, including breast cancer. In this Perspective, the first section describes the classification and mechanism of endocrine therapy drugs for ER+ breast cancer, and the second section summarizes research since 2000 into metal complexes with activity toward ER+ breast cancer. Finally, we discuss the opportunities, challenges, and future directions for metal complexes in the treatment of ER+ breast cancer.

Ionic mononuclear [Fe] and heterodinuclear [Fe,Ru] bis(diphenylphosphino)alkane complexes: Synthesis, spectroscopy, DFT structures, cytotoxicity, and biomolecular interactions

Iron(II) and Ru(II) half-sandwich compounds encompass some promising pre-clinical anticancer agents whose efficacy may be tuned by structural modification of the coordinated ligands. Here, we combine two such bioactive metal centres in cationic bis(diphenylphosphino)alkane-bridged heterodinuclear [Fe2+, Ru2+] complexes to delineate how ligand structural variations modulate compound cytotoxicity. Specifically, Fe(II) complexes of the type [(η5–C5H5)Fe(CO)2(κ1–PPh2(CH2)nPPh2)]{PF6} (n = 1–5), compounds 1–5, and heterodinuclear [Fe2+, Ru2+] complexes, [(η5–C5H5)Fe(CO)2(μ–PPh2(CH2)nPPh2))(η6–p–cymene)RuCl2]{PF6} (n = 2–5) (compounds 7–10), were synthesized and characterised. The mononuclear complexes were moderately cytotoxic against two ovarian cancer cell lines (A2780 and cisplatin resistant A2780cis) with IC50 values ranging from 2.3 ± 0.5 μM to 9.0 ± 1.4 μM. For 7–10, the cytotoxicity increased with increasing Fe⋅⋅⋅Ru distance, consistent with their DNA affinity. UV–visible spectroscopy suggested the chloride ligands in heterodinuclear 8–10 undergo stepwise substitution by water on the timescale of the DNA interaction experiments, probably affording the species [RuCl(OH2)(η6-p-cymene)(PRPh2)]2+ and [Ru(OH)(OH2)(η6-p-cymene)(PRPh2)]2+ (where PRPh2 has R = [−(CH2)5PPh2–Fe(C5H5)(CO)2]+). One interpretation of the combined DNA-interaction and kinetic data is that the mono(aqua) complex may interact with dsDNA through nucleobase coordination. Heterodinuclear 10 reacts with glutathione (GSH) to form stable mono- and bis(thiolate) adducts, 10-SG and 10-SG2, with no evidence of metal ion reduction (k1 = 1.07 ± 0.17 × 10−1 min−1 and k2 = 6.04 ± 0.59 × 10−3 min−1 at 37 °C). This work highlights the synergistic effect of the Fe2+/Ru2+ centres on both the cytotoxicity and biomolecular interactions of the present heterodinuclear complexes.

Preparation of 2D ZIF-L and Its Antibacterial and Antifouling Properties

The excessively leached metal ions from traditional metallic antimicrobial nanoparticles are harmful to biological and human tissues. Metal-organic frameworks (MOFs) coordinating bioactive metal ions to organic bridging ligands can potentially address this issue, avoiding the excessive leaching of metal ions and simultaneously exhibiting high effective antibacterial activities. Here, we report the preparation of a 2-dimensional leaves-like zeolitic imidazolate framework (ZIF-L) for potential antibacterial and anti-algae applications. The ZIF-L nanosheet exhibits complete inactivation of Escherichia coli (phosphate buffer saline: 4 h) and Bacillus subtilis (seawater: 0.5 h). The ZIF-L/epoxy composite has excellent antibacterial effect, poisoning effect and anti-adhesion effect on a variety of marine algae. It is worth noting that the removal rate (Escherichia coli) for ZIF/epoxy composite can be reached to 90.20% by only adding ZIF-L (0.25 wt%). This work will inspire researchers to develop more metal-organic frameworks materials for applications in the antibacterial and anti-algae fields.

ANTIFUNGAL AND ANTIOXIDANT ACTIVITIES OF COBALT AND NICKEL METAL COMPLEXES OF P-AMINO BENZAMIDE

Cobalt and nickel bio-active metal chelates were synthesized using p-aminobenzamide and thiocyanate ion in an equimolar ratio, and they were assessed for conductivity, UV-Visible, IR, and far-IR spectra as well as metal ion estimation identification. Based on their spectral and magnetic characteristics, the complexes were given octahedral geometry. The complexes are paramagnetic, monomeric, and non-electrolyte. With the help of the Agar Disc diffusion method using fluconazole as the reference drug, the antifungal activity of metal chelates through an in-vitro mechanism was compared with p-aminobenzamide against C. albicans. Metal(II) chelates' in-vitro DPPH free radical scavenging ability was tested and contrasted with that of standard ascorbic acid. The complexes appear to have moderate activity, according to the results of the computation of the IC50 values at four distinct concentrations.

Influence of bioactive metal fillers on antimicrobial properties of PA12 composites produced by laser-based powder bed fusion of polymers.

Purpose: This study investigated the influence of three types of metallic microfillers, spherical silver and spherical, and dendritic copper, on the ability of polyamide 12 (PA12) to inhibit microorganism growth on the surfaces of samples produced using laser-based powder bed fusion of polymers (PBF-LB/P). The aim of this study was to initially characterize these materials regarding their potential applicability for parts dedicated to use in the hospitals, where surfaces are periodically disinfected using chemical and/or physical measures. Methods: Composite powders with filler concentrations of 0.5, 1, 2 and 5% by weight were prepared using the mechanical mixing method and processed using PBF-LB/P. Three common hospital pathogens responsible for healthcare-associated infections: Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans were tested. Additionally, the safety of the composites was assessed through in vitro tests using human cell lines: keratinocytes and fibroblasts. Results: The research reveals that addition of copper or silver causes decrease in bacterial colony viability compared to the material without a filler, but an insignificant effect on antifungal properties. There was no significant impact within the tested range of filler's content on the antibacterial properties. Furthermore, a strong effect of the microfillers on tested material's toxicity is observed. Conclusions: The addition of metallic microfillers enhances the antibacterial response of polymeric materials processed with PBF-LB/P. Nevertheless, the observed varying levels of cytotoxicity toward eukaryotic cell lines underscore the need for further studies on the analysed materials to unequivocally determine their potential applicability as materials for short-term contact with human skin in a hospital setting.

Nitrogen limitation prevents the effects of iron or dust additions on biological carbon fixation in the Gulf of California

This paper reports the effect of dissolved iron (dFe) and dust additions on the Biological Carbon Fixation (BCF) rates in the surface layer of the central Gulf of California (GC). Two on deck experiments were conducted in the summer of 2016 at an oceanographic station located in the Guaymas Basin. Each experiment consisted in the incubation of natural phytoplankton assemblages collected at three distinct depths within the upper 50 m layer and amended either with iron (FeCl3) or dust leachate, followed by the quantification of BCF rates using the 13C assimilation method. A very warm (∼30 °C) water column strongly stratified and with reduced phytoplankton biomass (<1 mg chlorophyll a m−3) was indicative of an oligotrophic environment. In addition, the surface levels of NO3−+NO2− (<0.1 μM), dFe (1.71 ± 1.04 nM), as well as the Fe:N (78 ± 47 nmol μmol−1) and N:P (0.04 ± 0.01) ratios revealed that phytoplankton was under conditions of inorganic nitrogen limitation. BCF rates measured during the experiments ranged between 0.46 ± 0.04 and 6.24 ± 0.34 mg C m−3 h−1 with the highest values at the maximum of fluorescence and their vertical distribution was associated with the carbon biomass of picophytoplankton and diatoms. Despite the oligotrophic condition that predominated during the cruise, most of the Fe or dust additions did not show a significant effect (p > 0.05) on the magnitude of BCF rates, which was attributed to the fact that N, rather than Fe, was the limiting nutrient for phytoplankton production. However, Fe limitation cannot be completely ruled out as two samples (one for each treatment) showed a significant increase (p < 0.05) in BCF rates. We suggest that atmospheric supply of dust during the summer could play a relevant biological role maintaining high concentrations of dFe (and other bioactive metals) in the surface waters of central GC.

In English

The coronavirus pandemic has increased interest in antibacterial agents containing bioactive metals, for which zeolites are promising carriers. On the other hand, zeolite adsorbents and ion exchangers containing bioactive metals and endowed with bactericidal properties are promising for water treatment and other environmental and medical applications.Silver-, copper-, and zinc-containing microporous materials have been prepared on the base of natural analcime,phillipsite and heulandite from Georgian manifestations using ion-exchange reactions between zeolite microcrystals and a salt of a corresponding transition metal in the solid phase followed by washing with distilled water. Synthesized in such way adsorbent-ion-exchangers are characterized by chemical composition based on the X-ray energy dispersion spectra, powder X-ray diffraction patterns, Fourier transform infra-red spectra and low-temperature adsorption-desorption isotherms of N2. Obtained materials remain the zeolite crystal structure and contain 130–230 mg/g of silver, 65–72 mg/g of copper, and 58–86 mg/g of zinc, as compared with modified samples of synthetic type A zeolite containing up to 380 mg/g of silver, 150 mg/g of copper, and 150 mg/g of zinc. Prepared metal-containing materials show bacteriostatic activity against Gram negative bacterium Escherichia coli, Gram positive bacteria Staphylococcus aureus and Bacillus subtilis, fungal pathogenic yeastCandida albicans, and a fungus Aspergilusniger, and natural zeolites enriched with biometals exhibit a synergistic effect – their mixtures have a higher bacteriostatic activity. It is shown that mixtures of copper and zinc forms have a higher activity than the silver-containing form, which is very important from a practical point of view for replacing expensive silver with cheaper copper and zinc. It has been found that the bacteriostatic activity of metal-containing zeolites is determined not only and not so much by the ions of bioactive metals released into the liquid medium, but an important role ininhibiting the growth of microorganisms plays a type of zeolite matrix. Despite the relatively low ion-exchange capacity, heulandite turned out to be a fairly effective matrix for bioactive metals.

A study on Sr/Zn phytate complexes: structural properties and antimicrobial synergistic effects against Streptococcus mutans

Phytic acid (PA) is an abundant natural plant component that exhibits a versatility of applications benefited from its chemical structure, standing out its use as food, packing and dental additive due to its antimicrobial properties. The capacity of PA to chelate ions is also well-established and the formation and thermodynamic properties of different metallic complexes has been described. However, research studies of these compounds in terms of chemistry and biological features are still demanded in order to extend the application scope of PA complexes. The main goal of this paper is to deepen in the knowledge of the bioactive metal complexes chemistry and their bactericide activity, to extend their application in biomaterial science, specifically in oral implantology. Thus, this work presents the synthesis and structural assessment of two metallic phytate complexes bearing the bioactive cations Zn2+ and Sr2+ (ZnPhy and SrPhy respectively), along with studies on the synergic biological properties between PA and cations. Metallic phytates were synthesized in the solid-state by hydrothermal reaction leading to pure solid compounds in high yields. Their molecular formulas were C6H12024P6Sr4·5H2O and C6H12024P6Zn6·6H2O, as determined by ICP and HRES-TGA. The metal coordination bond of the solid complexes was further analysed by EDS, Raman, ATR-FTIR and solid 13C and 31P-NMR spectroscopies. Likewise, we evaluated the in vitro ability of the phytate compounds for inhibiting biofilm production of Streptococcus mutans cultures. Results indicate that all compounds significantly reduced biofilm formation (PA < SrPhy < ZnPhy), and ZnPhy even showed remarkable differences with respect to PA and SrPhy. Analysis of antimicrobial properties shows the first clues of the possible synergic effects created between PA and the corresponding cation in different cell metabolic processes. In overall, findings of this work can contribute to expand the applications of these bioactive metallic complexes in the biotechnological and biomedical fields, and they can be considered for the fabrication of anti-plaque coating systems in the dentistry field.

Development of Bioactive Metal Forming Technology and Optimization of Metal Additive Manufacturing Process

Development of Bioactive Metal Forming Technology and Optimization of Metal Additive Manufacturing Process

BIOORGANOMETALLIC FERROQUINE AND RELATED COMPOUNDS AS ANTIMALARIAL CHEMOTHERAPEUTIC AGENTS: A SHORT REVIEW

Drug resistant Plasmodium falciparum is a major threat to global health. Eradicating the parasite in endemic regions, especially sub-Saharan Africa is daunting. Milestones and a general target of 2030 have been set for this. However, funding and disruptions due to Ebola virus disease epidemic and COVID-19 pandemic are some of the cog in the wheel of the malaria eradication program. The recent WHO approval of the first malaria vaccine is a hope raiser and is expected to merely catalyze the eradication effort. Chemoprevention is a key malaria eradication strategy. Ferroquine, an organometallic chloroquine-ferrocene conjugate with effective antimalarial properties is capable of overcoming resistant strains and restoring chloroquine antimalarial properties. It has a novel mechanism of action. Like chloroquine, it forms complex with Fe(III)PPIX, strongly inhibit ß-hematin formation and drug accumulation in the acidic digestive vacuole. ferroquine is more lipophilic at cytosolic pH and cannot be pumped out of digestive vacuole thereby evading the chloroquine resistance mechanism. Clinical trials showed the drug candidate to be safe and tolerable. The ferroquine molecule can be conveniently synthesized via a reductive amination reaction involving a condensation of 7-chloroquinolin-4-amine and amino ferrocenyl aldehyde in a single stage procedure. It is well characterized. Studies revealed that covalently bonded chloroquine-ferrocene is responsible for the molecule's efficacy against P. falciparum. The pure chloroquine or ferrocene moieties are less active. Structural adjustments in amino group side chain, changes in position of the ferrocenyl organometallic group, substituting the Fe with other bioactive metals (Ru, Rh, Os) and substituting chloroquine for other organic molecules with antimalarial properties, all resulted in analogues with potent antimalarial properties similar to or better than chloroquine but not as effective as ferroquine.

Synthesis, spectroscopic characterization, molecular docking, as well as in vitro cytotoxicity of calcium-sulfasalazine complex

With the growing resistance of the bacterial strains resistant against antibiotics like sulfasalazine (SSZ) drug which has been of a great concern recently, bioactive metal complexation with an antibacterial agent “sulfasalazine” could be a potential solution in order to enhance the biocidal property of the drug. Herein, Calcium (II) sulfasalazine complex was experimentally synthesized and characterized by using infrared (IR) and UV–vis spectroscopic techniques. The complex was modeled using density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations in order to analyze its electronic and optical properties and thermodynamic parameters in gas and PCM (ethanol) environments and compare these results with those of the experimental results where relevant. Cell toxicity assay (MTT) indicated that the half-maximal inhibitory concentrations (IC50) of SSZ and its combination with Ca were has no significant toxicity at concentrations below 650 µM in HDF cell lines.

Evaluating the antimicrobial activity and cytotoxicity of polydopamine capped silver and silver/polydopamine core-shell nanocomposites

Fabrication of bioactive nanomaterials with improved stability and low toxicity towards healthy mammalian cells have recently been a topic of interest. Bioactive metal nanomaterials such as silver nanoparticles (AgNPs) tend to lose their stability with time and become toxic to some extent, limiting their biological applications. AgNPs were separately encapsulated and loaded on the surface of a biocompatible polydopamine (PDA) to produce Ag-PDA and [email protected] nanocomposites to unravel the issue of agglomeration. PDA was coated through the self-polymerization of dopamine on the surface of AgNPs to produce Ag-PDA core-shells nanocomposites. For [email protected], PDA spheres were first designed through self-polymerization of dopamine followed by in situ reduction of silver nitrate (AgNO3) without any reductant. AgNPs sizes were controlled by varying the concentration of AgNO3. The TEM micrograms showed monodispersed PDA spheres with an average diameter of 238 nm for Ag-PDA and [email protected] nanocomposites. Compared to [email protected], Ag-PDA nanocomposites have shown insignificant toxicity towards human embryonic kidney (HEK-293T) and human dermal fibroblasts (HDF) cells with cell viability of over 95% at concentration of 250 µg/mL. A excellent antimicrobial activity of the nanocomposites was observed; with [email protected] possessing bactericidal effect at concentration as low as 12.5 µg/mL. Ag-PDA on the other hand were only found to be bacteriostatic against gram-positive and gram-negative bacteria was also observed.

A Stimuli‐Responsive Small‐Molecule Metal‐Carrying Prochelator: A Novel Prodrug Design Strategy for Metal Complexes

AbstractSelective activation of prodrugs is an important approach to reduce the side effects of disease treatment. We report a prodrug design concept for metal complexes, termed “metal‐carrying prochelator”, which can co‐carry a metal ion and chelator within a single small‐molecule compound and remain inert until it undergoes a specifically triggered intramolecular chelation to synthesize a bioactive metal complex in situ for targeted therapy. As a proof‐of‐concept, we designed a H2O2‐responsive small‐molecule prochelator, DPBD, based on the strong chelator diethyldithiocarbamate (DTC) and copper. DPBD can carry Cu2+ (DPBD‐Cu) and respond to elevated H2O2 levels in tumor cells by releasing DTC, which rapidly chelates Cu2+ from DPBD‐Cu affording a DTC–copper complex with high cytotoxicity, realizing potent antitumor efficacy with low systemic toxicity. Thus, with its unique intramolecularly triggered activation mechanism, this concept based on a small‐molecule metal‐carrying prochelator can help in the prodrug design of metal complexes.

A Stimuli-Responsive Small-Molecule Metal-Carrying Prochelator: A Novel Prodrug Design Strategy for Metal Complexes.

Selective activation of prodrugs is an important approach to reduce the side effects of disease treatment. We report a prodrug design concept for metal complexes, termed "metal-carrying prochelator", which can co-carry a metal ion and chelator within a single small-molecule compound and remain inert until it undergoes a specifically triggered intramolecular chelation to synthesize a bioactive metal complex in situ for targeted therapy. As a proof-of-concept, we designed a H2 O2 -responsive small-molecule prochelator, DPBD, based on the strong chelator diethyldithiocarbamate (DTC) and copper. DPBD can carry Cu2+ (DPBD-Cu) and respond to elevated H2 O2 levels in tumor cells by releasing DTC, which rapidly chelates Cu2+ from DPBD-Cu affording a DTC-copper complex with high cytotoxicity, realizing potent antitumor efficacy with low systemic toxicity. Thus, with its unique intramolecularly triggered activation mechanism, this concept based on a small-molecule metal-carrying prochelator can help in the prodrug design of metal complexes.

C83 USE OF CANGRELOR IN A 63 YEARS OLD MEN SUFFERING FROM ACUTE INFERIOR ST–ELEVATION MYOCARDIAL INFARCTION AND SEVERE IDIOPATHIC THROMBOCYTOPENIC PURPURA: A CASE REPORT

Abstract A 63–year–old man suffering from systemic arterial hypertension, thalassemic trait, recent right ureteral stent implantation, dysthyroidism and thrombocytopenia presented to the Emergency Department with acute chest pain and ST elevation in inferior leads and 2nd degree atrioventricular block. He suffered from idiopathic thrombocytopenic purpura since February 2020, with baseline platelet level (PLT) &amp;lt;10,000/mm³ requiring treatment with deltacortene 5 mg, tranexamic acid 1000 mg x 3/day and fostamatimib 100 mg x 2/day. Upon arrival in the Cardiology Intensive Care Unit (UTIC) an echocardiogram was performed and confirmed inferior myocardial infarction. First laboratory results were significant for PLT of 9,000/mm³ and Troponin I peaked at 31,838 pg/mL. The patient received Acetylsalicylic acid (ASA) 300 mg iv then was urgently transported to the Cath–Lab. Coronary angiography revealed mid right coronary artery occlusion, subsequently underwent primary percutaneous coronary intervention with multiple pre–dilations and placement of dual 3.5x28mm and 4.0x28mm TiNO bioactive metal stent with excellent angiographic results. A temporary Pacemaker was implanted. It was started Cangrelor bolus 30 µ/kg followed by infusion at 4 µ/kg/min for 6 hours associated with unfractionated sodium heparin at a reduced dosage of 50 IU/kg during the procedure and with a subsequent switch to Clopidogrel after an oral bolus of 300 mg. After 24 hours, the patient removed the temporary PMK for resolution of the AV block. The haematologist consultant advised to increase fosfatimib to 150 mg x 2/day and recommended the use of Human Immunoglobulin iv from the second day of hospitalization for 2 days. The patient was discharged on the seventh day, asymptomatic, with dual antiplatelet therapy (DAPT) with ASA 100 mg and Clopidogrel 75 mg daily and did not experience any bleeding during hospitalization. At a one–month follow–up, the patient is symptomatic and continued to tolerate ASA and Clopidogrel with stable PLT of 11,000/mm³. In treating for STEMI, the treatment regimen consists of DAPT that increases risks for bleeding. In patients with thrombocytopenia, the risk for bleeding is multiplied and there are no clinical trials where patients with low platelet count are included, all therapeutic decisions must be made based on clinician’s experience and experts’ consensus. The use of Cangrelor proved to be safe and effective during STEMI even in patient with severe thrombocytopenia.

Nanoparticles of Bioactive Metals/Metal Oxides and Their Nanocomposites with Antibacterial Drugs for Biomedical Applications.

The increasing appearance of new strains of microorganisms resistant to the action of existing antibiotics is a modern problem that requires urgent decision. A promising potential solution is the use of nanoparticles of bioactive metals and their oxides as new antibacterial agents, since they are capable of affecting pathogenic microorganisms by mechanisms different from the mechanisms of action of antibiotics. Inorganic nanoparticles possess a wide spectrum of antibacterial activity. These particles can be easily conjugated with drug molecules and become carriers in targeted drug-delivery systems. This paper discusses the benefits and prospects of the application of nanoparticles from metals and metal oxides and their nanocomposites with antibacterial drugs.

Influence of bioactive metal fillers on microstructural homogeneity of PA12 composites produced by polymer Laser Sintering

In this paper, polyamide 12 (PA12) blends with three types of metallic fillers are tested, which differ in the type of material and its’ morphology. Low content mixtures are taken into consideration (0.5, 1.0, 2.0, 5.0 wt%), since a low impact on mechanical properties along with obtaining antibacterial properties are desired. The investigation focuses on filler distribution as well as the influence on microstructural homogeneity of the base material after processing with polymer Laser Sintering. Moreover, the influence of the filler content on the mechanical properties and fracture behaviour were examined. Processability PA12 with bioactive metal fillers was confirmed, and no significant changes in ductile behaviour of PA 12 were observed. An in-depth analysis of the effect of the filler on microstructural homogeneity was conducted.Graphical abstract

Co-doping of iron and copper ions in nanosized bioactive glass by reactive laser fragmentation in liquids.

Bioactive glass (BG) is a frequently used biomaterial applicable in bone tissue engineering and known to be particularly effective when applied in nanoscopic dimensions. In this work, we employed the scalable reactive laser fragmentation in liquids method to produce nanosized 45S5 BG in the presence of light-absorbing Fe and Cu ions. Here, the function of the ions was twofold: (i) increasing the light absorption and thus causing a significant increase in laser fragmentation efficiency by a factor of 100 and (ii) doping the BG with bioactive metal ions up to 4wt%. Our findings reveal an effective downsizing of the BG from micrometer-sized educts into nanoparticles having average diameters of <50 nm. This goes along with successful element-specific incorporation of the metal ions into the BG, inducing co-doping of Fe and Cu ions as verified by energy-dispersive X-ray spectroscopy (EDX). In this context, the overall amorphous structure is retained, as evidenced by X-ray powder diffraction (XRD). We further demonstrate that the level of doping for both elements can be adjusted by changing the BG/ion concentration ratio during laser fragmentation. Consecutive ion release experiments using inductively-coupled plasma mass spectrometry (ICP-MS) were conducted to assess the potential bioactivity of the doped nanoscopic BG samples, and cell culture experiments using MG-63 osteoblast-like cells demonstrated their cytocompatibility. The elegant method of in situ co-doping of Fe and Cu ions during BG nanosizing may provide functionality-advanced biomaterials for future studies on angiogenesis or bone regeneration, particularly as the level of doping may be adjusted by ion concentrations and ion type in solution.