Rapid, early, and accurate bedside diagnosis of bone infections is an urgent clinical need that remains unmet. Here, we present a fishnet-like two-dimensional magnetic nanozyme (FGDAI) that integrates three functional modules: a monolayer graphene oxide substrate providing a large reaction interface; an Fe3O4 interlayer conferring efficient magnetic enrichment; and two dense layers of Au@Ir nanoparticles furnishing abundant catalytic sites that act synergistically with the Fe3O4 to enable catalytic enhancement. This architecture delivers multiple signal amplification-"large reaction interface, magnetic enrichment, synergistic enhancement"-within an immunochromatographic assay (ICA), effectively overcoming the sensitivity and robustness limitations of traditional colorimetric ICAs when challenged by complex clinical matrices. In addition, wheat germ agglutinin (WGA) was immobilized on the 2D FGDAI surface via lyophilization as a universal peptidoglycan recognition molecule, enabling efficient, broad-spectrum bacterial binding and thereby mediating ultrasensitive, simultaneous ICA detection of two important bone-infection pathogens (Staphylococcus aureus and Pseudomonas aeruginosa). FGDAI-WGA-ICA completes testing in under 25min with a visual limit of detection of 10cells/mL, exhibiting high sensitivity and specificity for the target pathogens. Moreover, validation in a cohort of 83 synovial fluid samples showed high concordance with clinical reference methods, supporting its potential for real-time, bedside diagnosis of bone infections.

A bifunctional scaffold with photothermal-pyroelectric antibacterial and piezoelectric osteogenic activities for treating infected bone defects

Modified Masquelet technique using free vascularized fibula grafting for reconstruction of large bone defects after bone infection.

Myeloid immune checkpoint blockade overcomes antibiotic resistance in bone infection by enhancing efferocytosis and suppressing MSC PANoptosis.

ObjectivesOsteomyelitis (OM) represents a major clinical challenge in reconstructive surgery. It is characterized by chronic infection, impaired healing, and high treatment costs. Despite the high relevance, the local immune and regenerative microenvironment of infected human bone tissue remains insufficiently characterized. This study aimed to evaluate cytokine concentrations in osteomyelitic bone tissue.MethodsBone samples were collected intraoperatively from patients with sternal, vascular, and posttraumatic OM and compared to noninfected control tissue. Cytokine concentrations of IL-6, IL-8, MCP-1, osteopontin, and SPARC were quantified in tissue homogenates by enzyme-linked immunosorbent assays (ELISA). Bacterial pathogens were identified using routine clinical microbiological diagnostics, and cytokine profiles were compared across the OM subgroups.ResultsPathogen identification revealed Staphylococcus epidermidis as the most common isolate in sternal OM, while vascular OM exhibited a broader spectrum including S. epidermidis, Corynebacterium striatum, Enterobacter cloacae, and Proteus mirabilis. Posttraumatic OM showed both monomicrobial and polymicrobial infections. The concentrations of the examined cytokines were significantly elevated in OM. No significant differences were observed between OM subtypes for most cytokines, except for MCP-1, which was higher in sternal compared to vascular OM. Spearman analysis revealed strong positive correlations between IL-6, IL-8, and MCP-1, indicating a coordinated inflammatory response. Osteopontin correlated significantly with inflammatory cytokines, while SPARC correlated primarily with osteopontin but not with inflammatory cytokines.ConclusionsCytokine profiling demonstrated simultaneous activation of inflammatory and regenerative processes in OM. The preserved regenerative marker profile across OM subtypes supports individualized surgical strategies even in chronic infections. Distinct correlation patterns between inflammatory and regenerative cytokines suggest differential regulation of immune and repair mechanisms within infected bone tissue.

To evaluate clinical features, management, and outcomes of paediatric bone and joint infection (BJI) in a regional Australian hospital and assess weight-based oral antibiotic prescribing. We conducted a retrospective study of 171 children aged 0-18 years admitted with septic arthritis and/or osteomyelitis between 2011 and 2021. Cases were identified using ICD-10-AM codes, and data on clinical presentation, microbiology and treatment were extracted from medical records. Oral antibiotic doses were assessed against international evidence-based guidelines. A total of 171 children were included (median age 27 months); 59.6% were aged ≤ 5 years, and 13.5% identified as Aboriginal or Torres Strait Islander. Staphylococcus aureus was the most frequently identified pathogen overall (53/108, 49.1%), and Kingella kingae in children < 5 years of age (20/57, 35.1%). Severe disease occurred in 29.8%. Oral antibiotic doses were below international guideline recommendations in 43.3% of cases, mostly with amoxicillin-clavulanate and cephalexin. Relapse (4.1%) and long-term sequelae (6.1%) were infrequent. Paediatric BJI mostly occurred in young and in Aboriginal and Torres Strait Islander children. Oral antibiotic weight-based dosing was often lower than international guideline recommendations for BJI. These findings highlight the need for standardised antibiotic dosing in BJI and further studies to optimise dosing in children.

Oropharyngeal Kingella kingae DNA was identified in 16 of 16 children with proven K. kingae bone and joint infection (BJI) (sensitivity 100%; 95% confidence interval: 79-100) and in 33 of 112 with disproven K. kingae BJI (specificity 71%; 95% confidence interval: 61-79). Due to low specificity, we advocate against oropharyngeal K. kingae DNA testing as a diagnostic tool in children suspected of BJI.

Nanozyme-based catalytic therapeutics: Applications in infectious diseases, cancer therapy, and bone regeneration

Outcomes of single stage treatment of chronic bone infection in adults with antibiotic impregnated calcium sulphate beads; A single centre retrospective study with a mean follow-up of 5.5 years.

Infected bone defects remain one of the greatest challenges in orthopedics, as bacterial contamination and insufficient vascularization severely compromise regeneration. Here, we report the development of a multifunctional 3D-bioprinted scaffold composed of zinc ion (Zn 2+ ) functionalized silk fibroin methacryloyl (SFMA), histidine methacryloyl (HisMA), and nano-hydroxyapatite (nHAP), further loaded with endothelial progenitor cells (EPCs) to promote simultaneous antibacterial, angiogenic, and osteogenic responses. The photocrosslinkable SFMA/HisMA bio-ink reinforced with nHAP provided mechanical stability, controlled swelling and degradation, while Zn 2+ coordination endowed strong antibacterial activity against E. coli and S. aureus . EPCs adhered and proliferated on the scaffolds, markedly enhancing osteogenic differentiation, angiogenesis while suppressing oxidative stress, as evidenced by increased expression of OCN, RUNX2, COL1, OPN, VEGF and inhibited lipid and mitochondrial ROS levels. Proteomic profiling further revealed that EPC-loaded scaffolds orchestrate osteoblast protein expression, promoting immunoregulation and extracellular matrix (ECM) reconstruction to accelerate tissue regeneration. In a murine femoral infected defect model, EPC-loaded scaffolds suppressed pro-inflammatory cytokines, stimulated angiogenesis, and supported robust new bone formation, leading to accelerated defect repair confirmed by μCT and histological analyses. Together, these findings demonstrate that the EPC-loaded Zn 2+ functionalized SFMA/HisMA/nHAP scaffold integrates antibacterial defence with vascular and osteogenic stimulation, offering a promising translational strategy for the treatment of complex infected bone defects. Schematic illustration of material synthesis and application. Silk fibroin (SFMA) was modified with glycidyl methacrylate (GMA) to obtain silk fibroin methacryloyl (SFMA), while histidine was functionalized with acryloyl chloride to generate histidine methacryloyl (HisMA). SFMA and HisMA were then combined and coordinated with Zn 2+ ions and incorporated with nHAP to form the full component bioactive scaffold (SFMA/HisMA/nHAP/Zn 2+ ). The resulting material can be 3D-printed and loaded with endothelial progenitor cells (EPCs) to yield a multifunctional scaffold with antibacterial activity, pro-osteogenic and pro-angiogenic properties, favorable physicochemical characteristics, and excellent biocompatibility, making it a promising candidate for the treatment of infected bone defects. • Develops a EPCs loaded bioactive scaffold. • EPC-loaded scaffolds couple antibacterial activity with enhanced osteogenesis, angiogenesis, and ROS control in vitro. • EPC-loaded scaffold promotes recovery of mouse infected bone defect.

Multifunctional, enzyme/pH-responsive gelatin microspheres with aptamer-targeted antibacterial and ionic-mediated dual therapy for infected bone defects.

Sequential innate-osteoimmune regulation via a self-enhanced delivery system for repair of infectious bone defects

3D printed microporous titanium prosthesis for single implantation or combined with free flap for infected bone defects in the limbs: a single-center retrospective cohort study.

Infected bone defects pose a major clinical challenge because they typically involve severe infection, poor vascularization, and bone loss. Existing implant materials lack integrated functionality for long-term infection control and tissue regeneration. Here, a multifunctional nanozyme platform consisting of a 3D-printed titanium scaffold functionalized with an iron sulfide multiactivity nanozyme (ISMNzyme)-modified hydrogel is introduced. The platform leverages synergistic peroxidase-like, myeloperoxidase-like, and glutathione peroxidase (GSH-Px)-like activities, alongside the controlled release of Fe2+ and polysulfides. This dual mechanism induces ferroptosis-like bacterial death while concurrently promoting angiogenesis and osteogenesis. The platform represents a promising nanozyme-based strategy for the treatment of infected bone defects.

This study aimed to characterize the clinical spectrum and the bacteriological and microbiological etiology of pediatric primary subacute hematogenous osteomyelitis (PSAHO) and to evaluate a modern diagnostic approach for these infections. A single-center, 25-year retrospective review (2000-2025) of 107 consecutive cases of PSAHO was performed. Clinical presentation, traditional inflammatory markers, conventional cultures and nucleic acid amplification tests (NAATs) on blood, and bone and oropharyngeal samples were assessed. Most patients (73.8%) were <4 years. Fever was uncommon (15.9%), and inflammatory markers were frequently normal (white blood cell counts in 81.1%, C-reactive protein levels in 60.4%) and abnormal in 69.2% for erythrocyte sedimentation rates and in 53.8% for platelet count. Low diagnostic sensitivity of conventional blood (4.2%) and bone (25.7%) sample cultures has been reported. In contrast, a comprehensive NAAT-based approach identified or strongly suggested a pathogen in 44.9% of cases. Kingella kingae was the predominant pathogen in children under 4. Oropharyngeal PCR tests potentially identified the pathogen in another 20 cases, and its presence could be reasonably suspected in a further 68 (63.6%). MRI was essential for diagnosis, identifying all lesions, whereas the sensitivity of radiographs was low (<50%). All patients recovered completely, regardless of the management strategy. This study provides three critical advances for clinical practice: (1) PSAHO should be considered in a limping toddler even without fever or elevated inflammatory markers, and MRI is the imaging modality of choice; (2) NAATs are indispensable for etiologic diagnosis, revealing age-dependent pathogens; (3) Oropharyngeal PCR is a useful diagnostic adjunct.

Bone and joint infection in children can result in bone and joint damage, sepsis, and even death. Diagnosis is informed by the history, examination, and a suite of tests, including blood markers, radiographs, ultrasound, and MRI. This study aimed to identify the communication needs of families during diagnostic assessment of bone and joint infection. This was a qualitative study involving semi-structured interviews with children and families who had experienced diagnostic tests for bone and joint infection, and health professionals experienced in the care of affected children. A total of 21 families (four children; 21 parents) and 11 health professionals from 11 English and Welsh hospitals were interviewed. Data analysis was informed by thematic analysis. Families often felt highly anxious during diagnosis. Some described a disorderly diagnosis process, gaps or inconsistencies in information, and insensitive communication that contributed to their anxiety. Other families described more positive experiences, indicating how health professionals helped them feel prepared by providing an outline of timelines, the rationale for tests, and the potential need to adjust plans as new information became available. Participants recognized the importance of age-appropriate communication with children, and the involvement of play specialists in this process. The findings demonstrate the intense anxiety families experience during assessment of bone and joint infection, particularly when they are left to make sense of uncertainties by themselves, or when communication is unclear. Health professionals can support families during diagnosis by attending to both the information they provide and how it is provided, while acknowledging the uncertainties of the diagnosis process. Specifically, families valued explanations of the rationale for different clinical investigations and their timing, and advance discussion of the next steps and possible outcomes of diagnostic testing. When test results became available, families were also helped by clear follow-up plans, including in situations when the results were inconclusive.

Introduction Due to the steady increase in the number of primary total hip arthroplasties, the problem of eliminating periprosthetic joint infection (PJI) has become pressing. The rise of antimicrobial-resistant PJI pathogens significantly complicates and prolongs treatment, contributing to the development of chronic infection, sometimes with latent clinical manifestations. The aim of this study was to identify the microbial landscape characteristics in different types of hip joint PJI. Materials and Methods Microbiological studies of 96 patients with hip joint PJI were analyzed: Group 1 ( n = 16) with type I PJI; Group 2 ( n = 80) with type II and type III PJI. Patients in Group 1 underwent the DAIR procedure and those in Group 2 underwent two-stage revision hip replacement. Results A total of 103 microbial isolates were obtained from 96 patients: 16 (15.5 %) Gr(–) and 87 (84.5 %) Gr(+). Among Gr(+), MRSA, MRSE, and MRSH were detected in 18 isolates, and among Gr(–), ESBL+ was detected in 16 isolates. The predominant pathogens in the PJI structure were S. aureus (52.9 %), S. epidermidis (19.5 %), E. cloacae (37.5 %), P. aeruginosa (18.6 %), and E. coli (18.6 %). Associations were more common in type 1 PJI (25 %) than in chronic forms (18.4 %). Microbial associations were detected in 20 cases (19.4 %). Culture-negative infection (CNI) was detected in 16 patients (16.7 %) in both groups. Relapse of PJI in patients with microbial associations occurred in three cases (15 %). In CNI cases, recurrence developed in four cases (25 %). Discussion The growth of Gr(–) flora in early PJI exceeded that in the chronic one: 31.3 % and 9.2 %, respectively. DAIR is ineffective in such conditions. S. aureus , as a causative agent of bone and joint infections, exists in a quasi-dormant state which contributes to chronicity. Conclusion Gram-negative microorganisms and their associations dominate in the etiology of early PJI (type I), while gram-positive pathogens predominated in chronic types (types II and III). Culture-negative infection was a more common cause of early PJI than of chronic types (25.0 % and 16.1 %, respectively). No statistically significant differences were found between the groups in the detection of methicillin-resistant staphylococci or gram-negative bacteria ESBL+.

Background: Bone and joint infections (BJIs), including osteomyelitis, septic arthritis, and periprosthetic joint infections, typically require prolonged antimicrobial therapy and often involve complex outpatient management. Oritavancin, a long-acting lipoglycopeptide approved for the treatment of acute bacterial skin and skin structure infections caused by Gram-positive bacteria, has emerged as a potential off-label option for BJIs owing to its favourable pharmacokinetic and pharmacodynamic properties. Objectives: To provide a comprehensive overview of the pharmacological rationale, microbiological activity, and available clinical evidence supporting the use of oritavancin in BJIs. Methods: A comprehensive narrative review of the literature was performed using MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL), focusing on publications from 2011 to 2025. Observational studies, case series, and case reports describing the off-label use of oritavancin in BJIs were considered. Results: The available literature primarily consists of observational studies and real-world experiences. Eighteen studies met the inclusion criteria. Oritavancin was most frequently evaluated for osteomyelitis (n = 14 studies), prosthetic joint infections (n = 10) and septic arthritis (n = 5). Multi-dose regimens, typically including a 1200 mg loading dose followed by weekly doses of 800-1200 mg, were the most commonly described strategies. Reported clinical success rates generally ranged from approximately 70% to over 90%. Oritavancin was overall well tolerated, with adverse events being mostly mild and self-limiting. Conclusions: Current evidence suggests that oritavancin may represent an effective and well-tolerated off-label option for selected patients with Gram-positive BJIs. Its use may offer practical advantages, including reduced hospitalization and avoidance of prolonged intravenous antimicrobial therapy, particularly in patients for whom standard treatment approaches are challenging.

We report for the first time an epidemic of persistent and recurrent bone infection in a Late Triassic juvenile-dominated phytosaur community. Bone histology of long limb bones and dorsal ribs of nine out of 21 individuals of Colossosuchus techniensis revealed aggressive periosteal growth as represented by distinct crescentic zone(s) of radial fibrolamellar bone tissue in the form of a sunburst pattern of the vascular channels and extensive secondary resorption at the mid- and outer cortical region. We propose that this Colossosuchus community suffered an epigenetic disease influenced by some exogenous factors and/or environments. The possibility of various diseases is reviewed, and within an extant phylogenetic bracketing approach, the most probable cause is inferred to be bacterial infection, especially in the form of osteomyelitis. Alternating occurrences of normal and diseased bone tissue in several limb bones, albeit in several individuals, suggest that the bone infection was persistent and recurrent, and resulted in a suppressed immunodefence system and restricted mobility that ultimately caused the demise of the phytosaur community.

Bone and joint infections (BJI) remain among the most challenging conditions in orthopaedics due to their complex pathophysiology, frequent association with biofilm formation on bone and implant surfaces, and the rising prevalence of antibiotic-resistant pathogens. Conventional antibiotic therapies, although central to current clinical practice, are often limited by poor biofilm penetration, disruption of the host microbiota, and the increasing emergence of multidrug resistance, particularly in chronic infections such as osteomyelitis and prosthetic joint infections. This review provides a comprehensive exploration of bacteriophage therapy as a targeted, non-antibiotic strategy for the management of BJIs. Bacteriophages exhibit unique biological characteristics, including strict host specificity, self-amplifying antibacterial activity, and the capacity to disrupt biofilms through bacterial lysis and phage-derived enzymes. Evidence from in vitro investigations, animal models, and emerging clinical studies demonstrates the promising efficacy of phages and phage lysins against key BJI pathogens, particularly Staphylococcus aureus, with favourable safety profiles and encouraging rates of infection control, especially when used as adjuncts to surgery and antibiotics. Despite this potential, challenges such as narrow host range, variable pharmacokinetics, immunogenicity, and underdeveloped regulatory frameworks continue to limit widespread clinical adoption. Addressing these barriers through standardized phage selection, improved delivery strategies, combination therapies, and coordinated regulatory efforts will be critical to realizing the full therapeutic potential of phage-based interventions for antibiotic-resistant bone and joint infections.