Tailored Coatings for Enhanced Performance of Zinc-Magnesium Alloys in Absorbable Implants.

Absorbable metals exhibit potential for next-generation temporary medical implants, dissolving safely in the body during tissue healing and regeneration. Their commercial incorporation could substantially diminish the need for additional surgeries and complications that are tied to permanent devices. Despite extensive research on magnesium (Mg) and iron (Fe), achieving the optimal combination of mechanical properties, biocompatibility, and controlled degradation rate for absorbable implants remains a challenge. Zinc (Zn) and Zn-based alloys emerged as an attractive alternative for absorbable implants, due to favorable combination of in vivo biocompatibility and degradation behavior. Moreover, the development of suitable coatings can enhance their biological characteristics and tailor their degradation process. In this work, four different biodegradable coatings (based on zinc phosphate (ZnP), collagen (Col), and Ag-doped bioactive glass nanoparticles (AgBGNs)) were synthesized by chemical conversion, spin-coating, or a combination of both on Zn-3Mg substrates. This study assessed the impact of the coatings on in vitro degradation behavior, cytocompatibility, and antibacterial activity. The ZnP-coated samples demonstrated controlled weight loss and a decreased corrosion rate over time, maintaining a physiological pH. Extracts from the uncoated, ZnP-coated, and Col-AgBGN-coated samples showed higher cell viability with increasing concentration. Bacterial viability was significantly impaired in all coated samples, particularly in the Col-AgBGN coating. This study showcases the potential of a strategic material-coating combination to effectively tackle multiple challenges encountered in current medical implant technologies by modifying the properties of absorbable metals to tailor patient treatments.

Silver-releasing bioactive glass nanoparticles for infected tissue regeneration.

Bacterial infections represent a formidable challenge, often leaving behind significant bone defects post-debridement and necessitating prolonged antibiotic treatments. The rise of antibiotic-resistant bacterial strains further complicates infection management. Bioactive glass nanoparticles have been presented as a promising substitute for bone defects and as carriers for therapeutic agents against microorganisms. Achieving consistent incorporation of ions into BGNs has proven challenging and restricted to a maximum ion concentration, especially when reducing the particle size. This study presents a notable achievement in the synthesis of 10 nm-sized Ag-doped bioactive glass nanoparticles (Ag-BGNs) using a modified yet straightforward Stöber method. The successful incorporation of essential elements, including P, Ca, Al, and Ag, into the glass structure at the intended concentrations (i.e., CaO wt% above 20 %) was confirmed by EDS, signifying a significant advancement in nanoscale biomaterial engineering. While exhibiting a spherical morphology and moderate dispersity, these nanoparticles tend to form submicron-sized aggregates outside of a solution state. The antibacterial effectiveness against MRSA was established across various experimental conditions, with Ag-BGNs effectively sterilizing planktonic bacteria without the need for antibiotics. Remarkably, when combined with oxacillin or fosfomycin, Ag-BGNs demonstrated a potent synergistic effect, restoring antibacterial capabilities against MRSA strains resistant to these antibiotics when used alone. Ag-BGNs exhibited potential in promoting human mesenchymal stromal cell proliferation, inducing the upregulation of osteoblast gene markers, and significantly contributing to bone regeneration in mice. This innovative synthesis protocol holds substantial promise for the development of biomaterials dedicated to the regeneration of infected tissue.

Unraveling the mechanisms of inhibition of silver-doped bioactive glass-ceramic particles.

Infections are a major concern in orthopedics. Antibacterial agents such as silver ions are of great interest as broad-spectrum biocides and have been incorporated into bioactive glass-ceramic particles to control the release of ions within a therapeutic concentration and provide tissue regenerative properties. In this work, the antibacterial capabilities of silver-doped bioactive glass (Ag-BG) microparticles were explored to reveal the unedited mechanisms of inhibition against methicillin-resistant Staphylococcus aureus (MRSA). The antibacterial properties were not limited to the delivery of silver ions but rather a combination of antibacterial degradation by-products. For example, nano-sized debris punctured holes in bacteria membranes, osmotic effects, and reactive oxygen species causing oxidative stress and almost 40% of the inhibition. Upon successive Ag-BG treatments, MRSA underwent phenotypic and genomic mutations which were not only insufficient to develop resistance but instead, the clones became more sensitive as the treatment was re-delivered. Additionally, the unprecedented restorative functionality of Ag-BG allowed the effective use of antibiotics that MRSA resists. The synergy mechanism was mainly identified for combinations targeting cell-wall activity and their action was proven in biofilm-like and virulent conditions. Unraveling these mechanisms may offer new insights into how to tailor healthcare materials to prevent or debilitate infections and join the fight against antibiotic resistance in clinical cases.

Materials for restoring lost Activity: Old drugs for new bugs.

The escalation of bacterial resistance to conventional medical antibiotics is a serious concern worldwide. Improvements to current therapies are urgently needed to address this problem. The synergistic combination of antibiotics with other agents is a strategic solution to combat multi-drug-resistant bacteria. Although these combinations decrease the required high dosages and therefore, reduce the toxicity of both agents without compromising the bactericidal effect, they cannot stop the development of further resistance. Recent studies have shown certain elements restore the ability of antibiotics to destroy bacteria that have acquired resistance to them. Due to these synergistic activities, organic and inorganic molecules have been investigated with the goal of restoring antibiotics in new approaches that mitigate the risk of expanding resistance. Herein, we summarize recent studies that restore antibiotics once thought to be ineffective, but have returned to our armamentarium through innovative, combinatorial efforts. A special focus is placed on the mechanisms that allow the synergistic combinations to combat bacteria. The promising data that demonstrated restoration of antimicrobials, supports the notion to find more combinations that can combat antibiotic-resistant bacteria.

Silver-doped bioactive glass particles for in vivo bone tissue regeneration and enhanced methicillin-resistant Staphylococcus aureus (MRSA) inhibition.

Infection is a significant risk factor for failed healing of bone and other tissues. We have developed a sol-gel (solution-gelation) derived bioactive glass doped with silver ions (Ag-BG), tailored to provide non-cytotoxic antibacterial activity while significantly enhancing osteoblast-lineage cell growth in vitro and bone regeneration in vivo. Our objective was to engineer a biomaterial that combats bacterial infection while maintaining the capability to promote bone growth. We observed that Ag-BG inhibits bacterial growth and potentiates the efficacy of conventional antibiotic treatment. Ag-BG microparticles enhance cell proliferation and osteogenic differentiation in human bone marrow stromal cells (hBMSC) in vitro. Moreover, in vivo tests using a calvarial defect model in mice demonstrated that Ag-BG microparticles induce bone regeneration. This novel system with dual biological and advanced antibacterial properties is a promising therapeutic for combating resistant bacteria while triggering new bone formation.

Bioactive Glass Nanoparticles for Tissue Regeneration.

Sol-gel-derived bioactive glass nanoparticles have attracted special interest due to their potential as novel therapeutic and regenerative agents. Significant challenges are yet to be addressed. The fabrication of sol-gel-derived nanoparticles in binary and ternary systems with an actual composition that meets the nominal has to be achieved. This work addresses this challenge and delivers nanoparticles in a ternary system with tailored composition and particle size. It also studies how specific steps in the fabrication process can affect the incorporation of the metallic ions, nanoparticle size, and mesoporosity. Sol-gel-derived bioactive glass nanoparticles in the 62 SiO2-34.5 CaO-3.2 P2O5 (mol %) system have been fabricated and characterized for their structural, morphological, and elemental characteristics using Fourier transform infrared spectroscopy, X-ray diffraction analysis, scanning electron microscopy associated with elemental analysis, transmission electron microscopy, and solid-state nuclear magnetic resonance. The fabricated nanoparticles were additionally observed to form the apatite phase when immersed in simulated body fluid. This work highlights the effect of the different processing variables, such as the nature of the solvent, the order in which reagents are added, stirring time, and the concentrations in the catalytic solution on the controlled incorporation of specific ions (e.g., P and Ca) in the nanoparticle network and particle size.

Resurrection of antibiotics that methicillin-resistant Staphylococcus aureus resists by silver-doped bioactive glass-ceramic microparticles.

This work describes a novel strategy to combat methicillin-resistant Staphylococcus aureus (MRSA) via the reactivation of inert antibiotics. This strategy exploits a multifunctional system consisting of bioactive glass-ceramic microparticles with antibacterial properties combined with various antibiotics to kill MRSA. Specifically, sol-gel derived silver-doped bioactive glass-ceramic microparticles (Ag-BG) combined with antibiotics that MRSA resists such as oxacillin or fosfomycin, significantly decreased the viability of MRSA. Ag-BG also potentiated the activity of vancomycin on static bacteria, which are typically resistant to this antibiotic. Notably, the synergistic activity is restricted to cell-envelope acting antibiotics as Ag-BG supplementation did not increase the efficacy of gentamicin. Bacteria viability assays and electron microscopy images demonstrate that Ag-BG synergizes to restore antibacterial activity to antibiotics that MRSA resists. The low cytotoxicity previously studied against oral bacteria, together with the known regenerative properties presented in previous studies, and the unique antibacterial properties observed in this work when they are combined with antibiotics, make this multifunctional system a promising approach for healing infected tissue. STATEMENT OF SIGNIFICANCE: This study addresses a very significant issue in the field of antibiotic resistance presenting an innovative way to clear MRSA, by utilizing bioactive glass-ceramic microparticles in combination with antibiotics. Multifunctional glass-ceramic microparticles doped with silver ions (Ag-BG) have been previously observed to exhibit bioactive and antibacterial properties. In this study Ag-BG microparticles were observed to synergize with antibiotics restoring their sensitivity against MRSA. This research work presents a novel approach to resurrect ineffective antibiotics and render them effective against MRSA. Cytotoxicity to eukaryotic cells is not anticipated, as it has been previously observed that these microparticles can trigger hard and soft dental tissue regeneration, when they are utilized in certain concentrations. This study opens a new avenue in the treatment of multidrug resistance bacteria.

Fabrication and multiscale characterization of 3D silver containing bioactive glass-ceramic scaffolds.

In this work, we fabricated and characterized bioactive 3D glass-ceramic scaffolds with inherent antibacterial properties. The sol-gel (solution-gelation) technique and the sacrificial template method were applied for the fabrication of 3D highly porous scaffolds in the 58.6SiO2 - 24.9CaO - 7.2P2O5 - 4.2Al2O3 - 1.5Na2O -1.5K2O - 2.1Ag2O system (Ag-BG). This system is known for its advanced bioactive and antibacterial properties. The fabrication of 3D scaffolds has potential applications that impact tissue engineering. The study of the developed scaffolds from macro-characteristics to nano-, revealed a strong correlation between the macroscale properties such as antibacterial action, bioactivity with the microstructural characteristics such as elemental analysis, crystallinity. Elemental homogeneity, morphological, and microstructural characteristics of the scaffolds were studied by scanning electron microscopy associated with energy dispersive spectroscopy (SEM-EDS), transmittance electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and UV-visible spectroscopy methods. The compressive strength of the 3D scaffolds was measured within the range of values for glass-ceramic scaffolds with similar compositions, porosity, and pore size. The capability of the scaffolds to form an apatite-like phase was tested by immersing the scaffolds in simulated body fluid (SBF) and the antibacterial response against methicillin-resistant Staphylococcus aureus (MRSA) was studied. The formation of an apatite phase was observed after two weeks of immersion in SBF and the anti-MRSA effect occurs after both direct and indirect exposure.