Search Results (368)

Background: Immune aging is a complex process involving various cellular changes, such as a myeloid bias, decreased functional activity of immune cells, accumulation of senescent cells, and alterations in serum levels of bactericidal humoral factors. As believed, these changes contribute to increased susceptibility of older adults to infectious diseases. Myeloid cells are considered the first line of defense against bacterial invasion. However, it remains unclear whether the protective functions of myeloid cells diminish in active older adults and whether potential age-related changes are evolutionarily conserved across primates. Methods: In this study, myeloid cell populations from peripheral blood and bone marrow of cynomolgus macaques and human peripheral blood were analyzed across a broad age range for phenotypic and functional characteristics, e.g., E. coli phagocytosis, secretion of proinflammatory factors, genetic instability, and signs of cellular aging. Results: Despite minor interspecies phenotypic differences in granulocyte populations, both the quantity and functions of myeloid cells were remarkably stable during aging in both species. Myeloid cells maintained genetic stability, and high SA-β-Gal activity was observed, likely reflecting metabolic traits rather than age-related changes. Importantly, a predominant and age-independent role of humoral factors, rather than cellular mechanisms, was identified in the initial control of bacterial infection. Conclusions: These findings suggest that innate immune functions remain stable for a long time during aging in both species. Full article

Background: Postoperative infections remain a major complication in spinal surgeries involving intersomatic screws, often compromising osseointegration and long-term implant stability. Questions/Purposes: This study evaluated a nanotextured titanium oxide surface with nanopillar-like morphology designed to reduce bacterial colonization while preserving mechanical integrity and promoting bone integration. Methods: Ti₆Al₄V screws were studied in three batches: control, passivated with HCl and acid mixture treatment to obtain nanotopographies on the surfaces. To create the nanotopographies, the screws were treated with a 1:1 (v/v) sulfuric acid–hydrogen peroxide solution for 2 h. Surface morphology, roughness, wettability, and surface energy were analyzed by SEM, confocal microscopy, and contact angle measurements. Corrosion and ion release were assessed electrochemically and by ICP-MS, respectively. Mechanical behavior, cytocompatibility, mineralization, and antibacterial efficacy were evaluated in vitro. Osseointegration was analyzed in rabbit tibiae after 21 days by histology and bone–implant contact (BIC). Results: The treatment produced uniform nanopillars (Ra = 0.12 µm) with increased hydrophilicity (49° vs. 102° control) and higher surface energy. Mechanical properties and fatigue resistance (~600 N, 10 million cycles) were unaffected. Corrosion currents and Ti ion release remained low. Nanopillar surfaces enhanced osteoblast adhesion and mineralization and reduced bacterial viability by >60% for most strains. In vivo, Bone Index Contact (BIC) was higher for nanopillars (52.0%) than for HCl-treated (43.8%) and control (40.1%) screws, showing a positive osseointegration trend (p > 0.005). Conclusions: The proposed acid-etching process generates a stable, scalable nanotopography with promising antibacterial and osteogenic potential while maintaining the alloy’s mechanical and chemical integrity. Clinical relevance: This simple, scalable, and drug-free surface modification offers a promising approach to reduce postoperative infections and promote bone integration in spinal implants. 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

The leading cause of post-surgical hospital readmission is the emergence of hospital-acquired infections (HAIs), where surgical site infections (SSIs) constitute a substantial negative impact on patient outcome and contribute annual direct costs estimated to range from $28.4 billion to $45 billion in the U.S. To address the need for novel antimicrobial coating strategies, previous research has demonstrated that certain microbes can degrade poly(aspartic acid) (PAA)-based coatings, suggesting potential limitations of single-compound approaches that must be considered when designing antimicrobial surfaces. In this proof-of-concept study, we investigated whether ordered sequential coatings combining thermally synthesized PAA (tPAA) and oleic acid (OleA) might produce enhanced antimicrobial effects compared to individual compounds. Despite concerns regarding PAA biodegradability, the benefits of using PAA include low cytotoxicity and an ability to chelate metals such as calcium and facilitate bone mineralization and growth post-surgery. Using simple yet effective methods of surface coating applications which utilize tPAA and OleA, we investigated the potential of these ordered coatings to attenuate planktonic and sessile (biofilm) growth and development in Pseudomonas aeruginosa and Escherichia coli in vitro. Application of these ordered coatings resulted in up to 62% reduction in bacterial carrying capacity for P. aeruginosa and up to 43% reduction in biofilm mass relative to untreated controls. Further, confocal imaging via immunohistochemical labeling revealed methods for evaluating the impact of treatments targeting biofilm development through extracellular DNA quantification. Additionally, these coatings show dose-dependent cytotoxic effects against 3T3 mouse fibroblast cells. These preliminary findings, along with results derived from cytotoxicity assessment and physicochemical characterization via dynamic light scattering, suggest that ordered tPAA-OleA coating systems warrant further investigation as potential antimicrobial strategies, though additional validation, including testing against diverse clinical isolates, mechanistic studies, and in vivo evaluation, would be required before clinical application. 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

Background/Objectives: Osteosarcoma and Ewing sarcoma are the predominant malignant bone tumors of the lower limbs in children. With 5-year survival rates of 70–77% for localized disease, limb salvage with growth-compatible reconstruction has replaced amputation as the standard. This review aimed to synthesize current reconstruction strategies, propose an age-and defect-based decision algorithm, and highlight growth-preserving innovations for skeletally immature patients. Methods: This narrative review of surgical techniques—including rotationplasty, biological reconstruction (vascularized/non-vascularized fibula, allograft, recycled autograft, “hot dog” composite), bone transport, and endoprosthetic replacement (modular, extendable, 3D-printed)—was conducted, with a literature search covering January 1990 to October 2025 and emphasized pediatric studies published after 2020, emphasizing pediatric outcomes, complication profiles, and functional scores. Results: Across pediatric and mixed-age cohorts (typically n ≈ 10–30 per technique; median follow-up 3–10 years), rotationplasty demonstrated high durability with Musculoskeletal Tumor Society (MSTS) scores of 21–28/30, especially in children < 6 years. Biological reconstruction achieved >80% union in defects < 6 cm, while vascularized fibula grafts yielded 82–95% union for 6–15 cm defects. Bone transport produced reliable union for 3–15 cm defects but required prolonged fixation (40–60 days/cm) and had high pin-tract infection rates (50–60%). Extendable endoprostheses demonstrated 5-year prosthesis survival of 54–87%, while early joint-preserving 3D-printed implants improved MSTS scores from 17 to 28 points in a pediatric series (n = 7, mean follow-up 30 months). Conclusions: Personalized reconstruction guided by a child-centered algorithm optimizes oncologic control, skeletal growth, and long-term function. Emerging 3D-printed joint-preserving implants and noninvasive lengthening technologies promise further reduction in revisions and complications in pediatric limb salvage. Full article

Bone is a structurally complex and dynamic tissue that plays a crucial role in mobility and skeletal stability. However, conditions such as osteoporosis, osteoarthritis, trauma-induced fractures, infections, and malignancies often necessitate the use of orthopedic and dental implants. Despite significant progress in implant biomaterials, challenges such as bacterial infection, inflammation, and loosening continue to compromise implant longevity, frequently leading to revision surgeries and extended recovery times. Smart coatings have emerged as a next-generation solution to these problems by providing on-demand, localized therapeutic responses to microenvironmental changes around implants and promoting bone regeneration. Such coatings can minimize antibiotic resistance by enabling controlled, stimulus-triggered drug release. Although the idea of using pH-sensitivity as a tool to make smart coatings is not a new thought, there are no options currently good enough to enter clinical studies. This review provides a comprehensive overview of recent advances in pH-sensitive polymers, hybrid composites, porous architectures, and bioactive linkers designed to dynamically respond to pathological pH variations at implant sites. By investigating the mechanisms of action, antibacterial and anti-inflammatory effects, and roles in bone regeneration, it is shown that the ability to provide time-dependent drug release for both short-term and long-term infections, as well as keeping the environment welcoming to the bone cell growth and replacement, is not an easy goal to reach, even with a fully biocompatable, non-toxic, and semi-biodegradable (one that releases the drug, but does not fade away) coating material compound. Reviewing all available options, including their functions and failures, finally, emerging trends, translational barriers, and future opportunities for clinical implementation are highlighted, underscoring the transformative potential of bioresponsive coatings in orthopedic and dental implant technologies. Full article

Background/Objectives: Due to their biocompatibility and bone-like composition, calcium phosphate materials—especially hydroxyapatite (HAp)—have emerged as promising carriers for localized antibiotic delivery in bone regeneration. Here, we developed Hap-based composite microspheres using a simple wet-chemical method and incorporated multiple antibiotics to evaluate their release profiles and antibacterial potential for treating bone infections. Methods: In this study, uniform and porous composite microspheres composed of Hap and gelatin were synthesized via a simple wet-chemical method using a mixed calcium phosphate–gelatin solution. Results: The resulting gelatin–Hap microspheres (G-HAM) were systematically characterized to verify their crystalline structure, morphology, composition, and thermal stability. G-HAM exhibited a highly porous structure, making them well-suited for use as drug carriers. Four clinically relevant antibiotics—gentamicin, vancomycin, teicoplanin, and zyvox—were incorporated into the microspheres and evaluated for their release behavior and antibacterial performance against Staphylococcus aureus. The release profiles revealed an initial burst release within the first hour that exceeded the minimum inhibitory concentrations of all tested antibiotics, followed by a sustained release phase. Antibiotics containing carboxylic groups, such as vancomycin and teicoplanin, demonstrated stronger interactions with Hap, resulting in a more prolonged release. Antibacterial testing confirmed that the released antibiotics maintained their chemical stability and bioactivity. Furthermore, the combination of bioactive Hap and peptide-rich gelatin promoted osteoblast-like cell adhesion and proliferation, while cytotoxicity assays verified excellent biocompatibility. Conclusions: Overall, these G-HAM provide a promising platform that integrates controlled antibiotic release with osteoconductive potential for bone infection treatment and tissue regeneration. Full article

Craniofacial bone defects of critical size, caused by trauma, tumors, infections, or congenital maldevelopment, represent a major challenge in plastic and reconstructive surgery. Autologous bone grafting is considered the gold standard, but limitations such as donor site morbidity and limited availability have prompted the development of artificial bone tissue engineering scaffolds. In recent years, bioactive scaffolds have been increasingly utilized in favor of inert biomaterials due to their immunomodulation and osteoinduction capabilities. This review methodically summarizes loading strategies for the functionalization of scaffolds with bioactive components, including cell regulatory factors, drugs, ions, stem cells, exosomes, and components derived from human tissues or cells to promote bone regeneration. The following mechanisms are involved: (1) the polarization of macrophages (M1-M2 transition), (2) the dynamic regulation of bone metabolism, and (3) the coupling of osteogenesis and angiogenesis. This review focuses on innovative delivery systems, such as 3D-printed scaffolds, nanocomposites and so on, that enable spatiotemporal control of bioactive cargo release. These address key challenges, such as infection resistance, vascularization, and mechanical stability in the process of bone regeneration. In addition, the article discusses emerging technologies, including stem cells and exosome-based acellular therapies, which demonstrate potential for personalized bone regeneration. This review integrates immunology, materials science, and clinical needs, providing a roadmap for the design of next-generation bone tissue engineering scaffolds to overcome critical-sized bone defects. Full article

Background and Objectives: This prospective case series evaluated a treatment strategy in endodontic-periodontal lesions resulting from concurrent pulpal and periodontal infections. These present significant management challenges, particularly when they exhibit resistance to standard treatment modalities. Persistent microbial biofilms in regions like dentinal tubules and lateral canals can make it hard for healing to happen, even with good endodontic and periodontal care. Diode lasers have antibacterial and photobiomodulatory effects, but they are most often used as single-stage disinfection techniques. This pilot study evaluated a multi-stage diode laser protocol designed to enhance healing outcomes in refractory endo-perio lesions that had not responded to conventional treatment. Materials and Methods: Twelve patients (aged 20–60 years) with chronic endo-perio lesions, referred after unsuccessful earlier treatment, were treated utilizing a sequential diode laser regimen: Phase 1—Endodontic disinfection: Following canal instrumentation (0.75 W, pulsed mode, frequency 15 Hz, 200 μm fiber, 15 J dosage/20 s) using a 976 nm diode laser. Phase 2—Periodontal disinfection: Following SRP, intra-pocket (0.75 W, pulsed mode, frequency 15 Hz, 300 μm fiber, 3.75 J dosage/5 s) using a 976 nm diode laser; Phase 3—Post treatment photobiomodulation: After periodontal and endodontic therapy, photobiomodulation was applied using a 650 nm diode laser intra-pocket and in the periapical region (25 mW, continuous mode, 1.5 J dosage) to reduce postoperative inflammation and stimulate healing. Clinical parameters—probing depth (PD), bleeding on probing (BOP), and mobility—along with radiographic bone fill were recorded at baseline and after 6 months. Results: All twelve cases showed measurable within-patient improvements over the six-month follow-up. Median probing depth decreased from 7.6 mm to 6.0 mm, and median bleeding on probing declined from 0.9 to 0.3. Radiographically, partial bone fill was observed in all cases, with a median value of 58.3 percent. Postoperative pain decreased progressively over the first 24 h, with patients reporting mild discomfort by 24 h. No adverse events were recorded. Conclusions: Within the limitations of this small, uncontrolled pilot study, the multi-stage diode laser protocol was associated with clinical and radiographic improvements and low postoperative discomfort in refractory endo-perio lesions. These preliminary findings suggest that such a protocol may serve as a useful adjunct to conventional therapy. Larger, controlled studies are required to confirm these outcomes and determine long-term efficacy. Full article

Background/Objectives: A subset of individuals develops persistent symptoms following SARS-CoV-2 infection, including musculoskeletal (MSK) manifestations, a condition known as long COVID (LC). Emerging hypotheses suggest that chronic low-grade inflammation in LC may impair bone metabolism and compromise joint health. However, empirical evidence is limited, and the impact of LC on MSK health, particularly bone and joint integrity, is poorly understood. To determine the influence of LC on MSK function, including bone health, body composition, and joint integrity. Methods: A 12-month longitudinal prospective cohort feasibility study was conducted involving 45 adults with LC and 40 well-recovered (WR) post-COVID-19 controls. Baseline and follow-up assessments included dual-energy X-ray absorptiometry (DXA) for bone mineral density (BMD) and total body composition (TBC), alongside ultrasound of the hand and knee joints to evaluate intra-articular changes. Results: The LC group had more fat in the gynoid, android, and leg regions at each assessment point compared to the controls (p < 0.01). LC showed a significantly lower knee synovial hypertrophy at the baseline, 13.3% compared to WR 45% (p = 0.001), and a marginal improvement in hand synovial hypertrophy, over 12 months, from a median of 2 (IQR 1;5) to 1 (IQR 0;3) (p = 0.012), as observed via MSK ultrasound. No notable differences were found between groups regarding BMD, either in the LC group compared to the control group or overtime. Conclusions: This cohort study of LC adults and controls found no evidence of rapid bone loss; however, adiposity and joint symptoms suggest the need for ongoing monitoring. Future research should focus on MSK markers, muscle function, advanced imaging, and improving MSK health. Full article

Background/Objectives: Peri-implant diseases may occur around osseointegrated implants and lead to implant loss. Treatment strategies focus on infection control with decontamination of implant surfaces/pockets. Mechanical debridement (MD) is necessary to reduce biofilm, although it may have limited effects. Antimicrobial photodynamic therapy (aPDT) has been proposed to increase the potential of MD. The aim of this systematic review and meta-analysis is to evaluate aPDT in adjunct to MD versus MD as a single treatment. Methods: An electronic and hand literature search was performed in several databases up to March 2025 to include randomized controlled trials (RCTs). Risk of bias (RoB) was assessed by Cochrane Risk of Bias Tool for RCTs (RoB 2). A meta-analysis was performed with marginal bone level change (MBLc) as the primary outcome, and changes in probing depth (PD) and bleeding on probing (BOP) as secondary outcomes. Results: Eleven RCTs (1056 implants, 878 patients) were included. RoB was high: in 3 studies; some concerns: in 4 studies; low: in 4 studies. The included studies showed a high heterogeneity for MD/aPDT protocols and diagnostic criteria of peri-implant diseases. The meta-analysis revealed, for four studies, a significantly higher MBLc for test patients (M∆: 0.29, 95% CI 0.12, 0.46; p < 0.001) and a significantly higher BOP change (M∆ 5.59; 95% CI: 1.19, 9.86; p = 0.01). No significant difference was found at 6 months in terms of PD change between the test and control groups (M∆ 0.46; 95% CI −0.09, 1.02; p = 0.10). High heterogeneity (I² > 85%) for all three outcomes was found. Conclusions: High heterogeneity, diagnostic variability, and the low number of included studies increase the need of well-designed RCTs on the topic. Despite no conclusive evidence could be found, adjunctive aPDT showed a promising trend to improve MD results. Full article

Osteoarticular infections (OAIs), including osteomyelitis, septic arthritis, prosthetic joint infections, and facture-related infections, remain a major challenge due to biofilm formation and the prevalence of multidrug-resistant (MDR) pathogens. Although OAIs are predominantly caused by Staphylococcus aureus and coagulase-negative staphylococci, the increasing incidence of MDR Gram-negative infections adds further complexity to their management. Standard approaches, combining surgery and prolonged antibiotic therapy, frequently result in recurrence and poor outcomes. Bacteriophage (phage) therapy has emerged as a promising adjunct or alternative approach, offering high host specificity, replication at the infection site, and activity against biofilm-embedded bacteria. This review highlights recent advances in phage therapy for OAIs, focusing on administration routes (intravenous, intra-articular, topical, and oral) and on novel pharmaceutical delivery systems such as hydrogels, bone cements, microparticles, nanoparticles, and implant coatings. Preclinical and early clinical studies have analyzed phage stability, controlled release, and the synergistic effects of combined phage/antibiotic therapy. However, challenges remain regarding standardization, immunogenicity, and regulatory approval. Nonetheless, phage therapy shows promise for clinical translation as an adjunct or alternative to conventional treatments for OAIs. Well-designed clinical trials are urgently needed to confirm the efficacy of phage therapy, optimize delivery strategies, and integrate the treatments in routine practice. Despite encouraging outcomes for a successful clinical implementation, regulation and standardization of GMP production are required. Full article

Third molar extraction is a common oral surgical procedure that can be accompanied by challenges in wound healing and bone regeneration. Materials such as bone substitute materials (BSMs) and platelet-rich fibrin (PRF) are often used to support socket regeneration. This prospective randomized controlled split-mouth clinical trial compared PRF application combined with BSM versus PRF alone in patients requiring bilateral third molar extraction. A total of 15 patients underwent standardized osteotomy procedures, with sockets filled either with PRF alone (control group) or with BSM + PRF on opposite sides (test group) under general anesthesia and with patients blinded to the treatment allocation. Postoperative pain and swelling were measured over 7 days using a visual analog scale and anatomical distance measurements, respectively. Bone regeneration was evaluated using cone beam computed tomography (CBCT) scans after an average healing period of six months, with results showing no significant differences between groups in terms of postoperative pain or swelling (n = 12; 3 patients were lost to randomization). However, CBCT imaging revealed covered socket residuum (CSR)—non-mineralized areas within the socket—in the PRF only group, whereas the BSM + PRF group demonstrated more homogeneous and mineralized bone formation throughout the extraction sites (n = 8; 5 patients were lost to follow-up). These non-mineralized areas represent covered socket residuum within the extraction sockets, which poses a clinical risk of infection and may negatively affect the dental health of the adjacent second molar. Based on the presented findings, we recommend combining BSM with PRF to support bone regeneration and regulate the postoperative pain and swelling following third molar extraction. Nevertheless, further research is required to determine the most suitable BSM type in this regard. 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