Search Results (237)

Chrysin, a vital flavonoid found in fruits, vegetables, honey, and propolis, plays a significant role in the management of various pathogenesis. Its ability to reduce oxidative stress and mitigate inflammation is a reassuring factor in disease management. In addition, its role in various cancers has been demonstrated and it modulates cell signaling pathways, including inflammation, angiogenesis, apoptosis, autophagy, and the cell cycle. The literature was collected using search engines such as Google, Google Scholar, PubMed, and Scopus. Keywords included chrysin sources, antioxidant and anti-inflammatory activity, cardioprotective and hepatoprotective effects, as well as anti-diabetic, neuroprotective, anti-cancer, antimicrobial, and bone-protective roles. Research and review articles, along with relevant clinical trials published in English, were included. This narrative review summarizes the therapeutic potential of chrysin in the management of chronic diseases. Additionally, combination therapies of chrysin with other drugs/natural compounds provide synergistic benefits, leading to increased efficacy and lower toxicity. Despite its promising pharmacological activities, the clinical utility of chrysin remains limited due to its poor bioavailability, low solubility, limited permeability, and rapid metabolism. Overcoming these challenges will require the development of advanced formulations, mechanistic studies, and well-designed clinical trials to fully exploit chrysin’s potential role in disease management. Full article

Background/Objectives: Chronic bone infections require local antimicrobial delivery to achieve high drug concentrations while limiting systemic toxicity. Silver ion-doped calcium phosphate synthetic bone grafts have been proposed as carriers for local antimicrobial release. This study aimed to evaluate the efficacy and safety of a silver ion-doped synthetic bone graft in patients with chronic osteomyelitis, infected nonunion, or implant-related bone infection. Methods: This retrospective cohort included 12 adults who underwent surgery for chronic osteomyelitis or implant-associated infection. All patients received thorough debridement, removal of infected implants when present, and filling of bone defects with a silver ion-doped calcium phosphate graft. The median age was 38 years, and follow-up was 12 months. Clinical and radiographic outcomes, liver and kidney function tests, and blood silver levels were assessed pre- and postoperatively. Results: Infection eradication was achieved in 11 of 12 patients (90%) at 12 months. Functional recovery, defined as return to normal daily activities, occurred within 3–5 months. Bone union was observed in all but one patient within 3–6 months, and no graft resorption was detected at one year. No significant differences in liver or kidney function tests were found compared with the control group (p > 0.05), and blood silver levels remained within normal limits. Conclusions: At 12-month follow-up, silver ion-doped synthetic bone grafts showed encouraging safety and efficacy in the treatment of chronic osteomyelitis. These findings suggest that silver-doped grafts may represent a useful option for one-stage treatment of osteomyelitis. Full article

Background: Antibiotic-loaded bone cement (ALBC) is widely used for local antibiotic delivery in joint arthroplasty to prevent and treat prosthetic joint infections (PJIs). In this study, we evaluated the efficacy of cemented Kirschner (K)-wires coated with various ALBC formulations using a Galleria mellonella infection model against multidrug-resistant (MDR) Staphylococcus aureus and Enterococcus faecalis. Methods: We tested commercially available bone cements, including gentamicin-only formulations (PALACOS R+G) and dual-antibiotic formulations, combining gentamicin with either clindamycin (COPAL G+C) or vancomycin (COPAL G+V), alongside an antibiotic-free control (PALACOS R). In vitro assays—including minimum inhibitory/bactericidal concentration (MIC/MBC) determination, antibiotic release kinetics, agar diffusion, and antibiofilm evaluations—demonstrated effective antibiotic release and significant antimicrobial activity against both planktonic and biofilm-associated bacteria. Results: In vivo, ALBC-coated K-wires were well tolerated in G. mellonella and significantly protected the larvae from S. aureus infection compared to controls. Notably, dual-antibiotic formulations provided superior protection, correlating with substantial reductions in bacterial colonisation on implant surfaces and in surrounding tissues. Conclusions: These findings support the utility of the G. mellonella model as a high-throughput, cost-effective platform for the preclinical evaluation of antimicrobial strategies to prevent and treat PJIs and further demonstrate the effectiveness of dual-loaded ALBC against multidrug-resistant bacteria. Full article

In this research, aluminium-doped biphasic calcium phosphate (Al-BCP) was synthesized by co-precipitation and formulated with hydrolyzed collagen and acetylsalicylic acid (ASA) to yield composites designed as a new class of bone-regenerative biomaterials with enhanced biological performance. Undoped and Al-modified powders (5/10 wt% Al precursor) were prepared at 40 °C (pH ~ 11) and calcined at 700 °C, and composites were produced at a 1:1:0.1 mass ratio (ceramic–collagen–ASA). Structure and chemistry were assessed by X-ray diffraction (XRD), Fourier-transform infrared (FTIR) and Raman spectroscopies, and X-ray photoelectron spectroscopy (XPS). Morphology and elemental distribution were examined by scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDX). Biological performance was preliminarily evaluated using HaCaT (immortalized human keratinocytes) viability and antibacterial assays against Staphylococcus aureus and Escherichia coli. XRD confirmed a biphasic hydroxyapatite/β-tricalcium phosphate system and showed that Al incorporation shifted the phase balance toward hydroxyapatite (HAp fraction 54.8% in BCP vs. ~68.6–68.7% in Al-doped samples). FTIR/Raman preserved BCP vibrational signatures and revealed collagen/ASA bands in the composites. XPS/EDX verified the expected composition, including surface N 1s from organics and Al at ~2–5 at% for doped samples, with surface Ca/P ≈ 1.15–1.16. SEM revealed multigranular microstructures with homogeneous Al distribution. All composites were non-cytotoxic (≥70% viability); M_Al10_Col_ASA exceeded 90% viability at 12.5% dilution. Preliminary antibacterial assays against Gram-positive and Gram-negative strains showed modest, time-dependent reductions in CFU relative to controls. These results corroborate the compositional/structural profile and preliminary biological performance of Al-BCP–collagen–ASA composites as multifunctional bone tissue engineering materials that foster a bone-friendly microenvironment, warranting further evaluation for bone regeneration. Full article

Background: Carbapenem-resistant Enterobacterales and difficult-to-treat resistance (DTR) Pseudomonas aeruginosa are a growing public health issue. Cefiderocol demonstrated activity against β-lactamase-producing Gram-negative bacteria (GNB). However, bone PharmacoKinetics (PK) data is lacking. Here, we report a case of post-traumatic chronic osteomyelitis caused by extensively drug-resistant (XDR) Pseudomonas aeruginosa which was successfully treated with cefiderocol. Moreover, we conducted a non-systematic review of the available literature. Case Report: We described the case of a 64-year-old man who was admitted to a traumatology ward after a work accident caused crushing of his left foot. Microbiological tests on intraoperative biopsies demonstrated XDR P. aeruginosa and K. oxytoca. Despite the administrations of different antibiotics regimens and multiple surgical revisions, the patient developed chronic osteomyelitis. To prevent amputation, cefiderocol was prescribed for six weeks, resulting in a complete clinical resolution of osteomyelitis. Review of the Literature: We performed a non-systematic review of the literature searching the public databases PubMed and Google Scholar. We identified nine case reports. In most patients (60%) the cause of osteomyelitis was post-surgical, and all the reported cases were healthcare associated. Osteomyelitis treatment required both antimicrobial therapy and surgery in all the cases described. Cefiderocol was often prescribed in association with other antibiotics (70%). Clinical cure was described in all the reported cases. Conclusions: This study highlights that cefiderocol is safe and efficacious to treat osteomyelitis caused by carbapenem-resistant GNB. However, evidence is limited to a few case reports. Full article

In this study, eco-friendly sheep hydroxyapatite (KHO) powder was produced from sheep femur bone waste. Hybrid composite powders were prepared by adding varying amounts of MgO and MgO–graphene to the produced sheep hydroxyapatite powders and sintering them at 1200 °C for 5 min using induction sintering. The physical, mechanical, microstructural, in vitro bioactivity, cell culture, and antibacterial properties were studied. According to the results of the study, the density and compressive strength values of the samples containing 1 wt.% MgO and 1 wt.% MgO–0.1 graphene (KHM1 and KHM1GRF0.1), which had the best density and compressive strength values, were determined to be 2.771 g/cm³–28.42 MPa and 2.636 g/cm³–26.25 MPa, respectively. According to the in vitro bioactivity test in simulated body fluid, these composites exhibited bioactivity, with a dense hydroxy carbona apatite layer forming. Moreover, according to the cell culture and antibacterial test results, it was determined that sheep-derived hydroxyapatite, resulting from induction sintering with MgO and graphene, exhibited excellent biocompatibility, enhanced osteogenic potential, and moderate antimicrobial activity. In summary, these sheep hydroxyapatite hybrid composites exhibited higher mechanical strength and excellent integrated biological performance, confirming their substantial potential as advanced biomaterials for bone regeneration. Full article

Hydrogels are versatile biomaterials for controlled drug delivery and tissue regeneration due to their biocompatibility and tunable degradation. Hydrogel was synthesized with a gelatin type A/polyvinyl alcohol functionalized with aqueous extract of roasted green tea (10% w/v) and evaluated its physiobiological performance in vitro. Degradation was assessed under enzymatic (collagenase II, trypsin) and hydrolytic conditions; swelling was performed with distilled water, cytocompatibility was tested on human periodontal ligament stem cells by MTT; antibacterial activity was measured against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The hydrogel showed complete hydrolytic degradation within 60 min and enzymatic degradation within 70 min, the hydrogel increased its mass by approximately 6.3 times relative weight, reached its maximum swelling in the range of 478–537%, (19% for the experimental group), while maintaining PDLSC viability (>80%). It exhibited significant antibacterial activity (inhibition: S. aureus 78.6%, S. mutans 67.4%, E. coli 73.2%). Importantly, in osteogenic medium, the hydrogel enhanced osteogenic differentiation of PDLSCs, evidenced by increased calcium deposition and positive Alizarin Red staining versus controls. These data position the gelatin/PVA/roasted green tea hydrogel as a bioactive, resorbable candidate for dental applications—particularly as an antimicrobial dressing and adjunct for periodontal bone regeneration material. Full article

Sodium butyrate has been documented to support gut function and help control pathogens in the gastrointestinal tract. However, the precise mechanisms of dietary sodium butyrate’s control over enteric pathogens in chickens remain unclear. Our study demonstrated that priming chicken bone marrow-derived macrophages (BMDMs) or the HD11 cell line with 1 mM sodium butyrate significantly enhanced their antimicrobial capacity against key bacterial pathogens (Escherichia coli, Salmonella Typhimurium, Pseudomonas aeruginosa, and Staphylococcus aureus) in gentamicin protection assays (p < 0.05; ≥1 log reduction in CFU/mL). This in vitro enhancement was associated with increased production of reactive oxygen species (ROS), as detected by DCFH-DA assays, showing approximately a 30% increase in HD11 cells and a 12% increase in BMDMs. Butyrate priming was observed to result in autophagy activation, potentially through mTOR pathway inhibition, evidenced by changes in related gene expression using RT-qPCR assay and a 2.5-fold increase in GFP-LC3B accumulation. Supporting this, pharmacological inhibition of ROS using the ROS scavenger N-acetyl-L-cystine (NAC) or autophagy with chloroquine reduced the butyrate-enhanced bacterial clearance. Furthermore, the mTOR inhibitor rapamycin synergized with butyrate priming, whereas the mTOR activator L-leucine counteracted enhanced antimicrobial activity. These findings offer crucial insights for improving host defence against bacterial infections and developing novel therapeutic strategies in chickens. Full article

This research investigated the feasibility of producing strontium-doped nanocrystalline hydroxyapatite (SrHAp) through an environmentally benign synthesis approach and evaluated the antimicrobial activity of the resulting material. The synthesized nanomaterial was subjected to comprehensive characterization. The antimicrobial efficacy of SrHAp was tested against Gram-positive and Gram-negative bacterial strains. X-ray diffraction (XRD) analysis in combination with Fourier-transform infrared (FT-IR) spectroscopy confirmed the successful formation of pure monocrystalline SrHAp. The scanning electron microscopy (SEM) examination revealed two predominant morphological structures: nanorods and prismatic configurations of the SrHAp. Transmission electron microscopy (TEM) demonstrated that the rod-like SrHAp nanocrystals aggregate into elongated grain structures with a size of about 25 nm × 10 nm. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis confirmed the presence and quantification of the concentrations of calcium, strontium, and phosphorus, while confirming the expected calcium–phosphorus ratio characteristic of hydroxyapatite. The study established that the positive surface charge of the material, with a point of zero charge near pH 10, is essential for its antimicrobial efficiency. These results suggest that SrHAp nanomaterials hold promise for biomedical applications, particularly as antimicrobial coatings for implants and scaffolds for bone tissue, where the prevention of infection is critical. Overall, despite its selective and material quantity-dependent antimicrobial efficacy, environmentally friendly synthesized SrHAp can be successfully applied as an effective controller of targeted microbial contamination, especially of Gram-positive bacterial species S. aureus, L. monocytogenes, S. Enteritidis, and A. baumanii. Full article

Background/Objectives: A comparative study of silver (Ag), titanium nitride (TiN), zirconium nitride (ZrN), and copper (Cu) coatings on titanium (Ti) disks, considering the specifications of a microporous skin- and bone-integrated titanium pylon (SBIP), was performed to assess their biocompatibility, osseointegration, and mechanical properties. Methods: To assess cytotoxicity and biocompatibility, Ti disks with various metal coatings were co-cultured with FetMSCs and MG-63 cells for 1, 3, 7, and 14 days and subsequently evaluated using a cell viability assay, as supported by SEM and confocal microscopy studies. The antimicrobial activity of the selected four materials coating the implants was tested against S. aureus by mounting Ti disks onto the surface of LB agar dishes spread with a bacterial suspension and measuring the diameter of the growth inhibition zones. Quantitative Real-Time Polymerase Chain Reaction (RT-PCR) analysis of the relative gene expression of biomarkers that are associated with extracellular matrix components (fibronectin, vitronectin, type I collagen) and cell adhesion (α2, α5, αV integrins), as well as of osteogenic markers (osteopontin, osteonectin, TGF-β1, SMAD), was performed during the 14-day follow-up period. Additionally, the activity of matrix metalloproteinases (MMP-1, -2, -8, -9) was assessed. Results: All samples with metal coatings, except the copper coating, demonstrated a good cytotoxicity profile, as evidenced by the presence of a cellular monolayer on the sample surface on the 14th day of the follow-up period (as shown by SEM and inverted confocal microscopy). All metal coatings enhanced MMP activity, as well as cellular adhesion and osteogenic marker expression; however, TiN showed the highest values of these parameters. Significant inhibition of bacterial growth was observed only in the Ag-coated Ti disks, and it persisted for over 35 days. Conclusions: The silver-based coating, due to its high antibacterial activity, low cytotoxicity, and biointegrative capacity, can be recommended as the coating of choice for microporous titanium implants for further preclinical studies. Full article

Zanthoxyli Pericarpium (ZP), the dried pericarp of mature fruits of Zanthoxylum schinifolium Siebold and Zucc., has traditionally been used in East Asian medicine for its medicinal properties, but its therapeutic potential in periodontitis has not been elucidated. In the present study, we investigated the effects of ZP on ligature-induced experimental periodontitis (EPD) in male Sprague Dawley rats. Animals were assigned to vehicle control, ligature control, ZP-treated (25, 50, and 100 mg/kg), or indomethacin-treated (5 mg/kg) groups (n = 10 per group) and orally administered the respective treatments daily for 10 days after ligature placement. ZP significantly reduced anaerobic bacterial proliferation and inflammatory cell infiltration in gingival tissue. ZP suppressed the production of inflammatory mediators, such as tumor necrosis factor-α and interleukin-1β, in both gingival tissues and lipopolysaccharide-stimulated RAW 264.7 macrophages, through inhibition of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. In addition, ZP decreased myeloperoxidase activity and reduced matrix metalloproteinase-8 expression, thereby preserving collagen areas. ZP also restored the receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) balance, leading to a reduction in osteoclast numbers and their occupancy on the alveolar surface, and it effectively ameliorated horizontal alveolar bone loss. Furthermore, ZP exhibited antioxidant effects by lowering malondialdehyde levels and inducible nitric oxide synthase activity in gingival tissues. Statistical analysis was performed using ANOVA followed by a post hoc test, with significance set at p < 0.05. These findings indicate that ZP mitigates periodontitis through combined antimicrobial, anti-inflammatory, antioxidant, and anti-resorptive actions, supporting its potential as a therapeutic candidate for periodontitis. Full article

Nanobiocomposites are a class of biomaterials that include at least one phase with constituents in the nanometer range. Nanobiocomposites, a new class of materials formed by combining natural and inorganic materials (metals, ceramics, polymers, and graphene) at the nanoscale dimension, are expected to revolutionize tissue engineering and bone implant applications because of their enhanced corrosion resistance, mechanical properties, biocompatibility, and antimicrobial activity. Titanium-based nanocomposites are gaining attention in biomedical applications due to their exceptional biocompatibility, corrosion resistance, and mechanical properties. These composites typically consist of a titanium or titanium alloy matrix that is embedded with nanoscale bioactive phases, such as hydroxyapatite, bioactive glass, polymers, or carbon-based nanomaterials. Common methods for synthesizing Ti-based nanobiocomposites and their parts, including bottom-up and top-down approaches, are presented and discussed. The synthesis conditions and appropriate functionalization influence the final properties of nanobiomaterials. By modifying the surface roughness at the nanoscale level, composite implants can be enhanced to improve tissue integration, leading to increased cell adhesion and protein adsorption. The objective of this review is to illustrate the most recent research on the synthesis and properties of Ti-based biocomposites and their scaffolds. Full article

Bone tissue restoration requires biomaterials, which combine osteoinductivity and the capability to prevent surgical site infections. Magnesium-substituted biphasic calcium phosphate (Mg-BCP) represents a promising solution, as magnesium substitution increases the biodegradation rate of calcium phosphate ceramics and provides inherent antibacterial properties. This study aimed to achieve wet precipitation synthesis of magnesium-substituted (1–10 mol%) biphasic calcium phosphate and to evaluate its drug delivery potential and antibacterial performance. Porous Mg-BCP granules were fabricated via the gelation of Mg-BCP suspension in sodium alginate followed by polymer removal. Drug delivery potential was evaluated using methylene blue as a model compound, with methylcellulose encapsulation implemented to ensure prolonged release. Magnesium content directly ruled the phase composition: low concentrations (1%) favored hydroxyapatite phase prevalence, while higher concentrations led to the β-tricalcium phosphate formation. Further assessment of drug delivery potential revealed that direct drug loading resulted in burst release, whereas methylcellulose encapsulation successfully enabled prolonged drug delivery. Mg-5BCP formulation demonstrated significant antimicrobial activity with growth inhibition of 17.7 ± 4.1% against C. albicans, 20.8 ± 7.0% against E. faecalis, and 12.9 ± 7.5% against E. coli. Therefore, Mg-5BCP–methylcellulose composite granules present a versatile platform for antibacterial drug delivery for bone tissue engineering applications. Full article

Matrix metalloproteinases (MMPs) are a family of endopeptidases recognized for their involvement in the degradation of the extracellular matrix and their important role in the pathogenesis of periodontitis. This chronic inflammatory condition causes the degradation of dental supporting tissues, resulting in bone loss. In patients with periodontitis, the expression and activation of MMPs, especially MMP-8 and MMP-9, significantly influence tissue degradation. In periodontitis treatment, various natural or synthetic metalloproteinase inhibitors (MMPIs) and antibiotics are used in sub-antimicrobial doses. However, while the evidence supports a role for MMPIs in reducing inflammation, preserving connective tissue, and improving the results of conventional periodontitis treatment, their clinical application is limited. In this review, we summarize MMPIs, their characteristics, and the mechanisms of action that may support their use in the treatment of periodontitis. In conclusion, MMPIs are a therapeutic alternative with great potential in the management of periodontitis, especially when combined with mechanical treatments, although further research is needed to optimize their clinical use. Full article

One of the main challenges in hydroxyapatite research is to develop cost-effective synthesis methods that consistently produce materials closely resembling natural bone, while maintaining high biocompatibility, phase purity, and mechanical stability for biomedical applications. Traditional synthetic techniques frequently fail to provide desirable mechanical characteristics and antibacterial activity, necessitating the development of novel strategies based on natural precursors and selective ion doping. The present study aims to explore the possibility of synthesizing hydroxyapatite through the co-precipitation method, followed by a microwave-assisted hydrothermal maturation process. The main CaO sources selected for this study are eggshells and mussel shells. Cu²⁺ and Sr²⁺ ions were added into the hydroxyapatite structure at concentrations of 1% and 5% to investigate their potential for biomedical applications. Furthermore, the morpho-structural and biological properties have been investigated. Results demonstrated the success of hydroxyapatite synthesis and ion incorporation into its chemical structure. Moreover, HAp samples exhibited significant antimicrobial properties, especially the samples doped with 5% Cu and Sr. Additionally, all samples presented good biological activity on MC3T3-E1 osteoblast cells, demonstrating good cellular viability of all samples. Therefore, by correlating the results, it could be concluded that the undoped and doped hydroxyapatite samples are suitable biomaterials to be further applied in orthopedic applications. Full article