This study represents the largest single-center cohort to date evaluating the early- and mid-term safety and effectiveness of a staged reconstructive strategy using 3D-printed microporous titanium prostheses, applied either alone or in combination with free flap reconstruction, for the management of infected bone defects. Patients treated between January 2019 and January 2025 were retrospectively identified from electronic medical records. Primary outcomes included changes in Visual Analogue Scale (VAS) scores and Lower Extremity Functional Scale (LEFS) scores at 3, 6, and 12 months, as well as at the last follow-up. Secondary outcomes included implant integration, postoperative functional recovery milestones for lower-extremity cases, and complication profiles. This study included 80 consecutive patients (54 males, 26 females) with an average age of 47.5 ± 9.3 years and an average follow-up time of 40.8 ± 14.8 months. At follow-up time points of 3 months and beyond, VAS scores significantly decreased compared to preoperative levels (p < 0.0001), and lower extremity LEFS scores significantly improved (p < 0.0001). At 12 months postoperatively, 69 cases (86.3

Objective:To summarize the clinical experiences of using Zeta-focal bone lengthening to treat bone defects caused by fracture-related infection (FRI) in two cases, and to preliminarily explore its feasibility and efficacy. Methods:In 2023, two male patients with bone defects caused by FRI were treated, aged 19 and 40 years, respectively. After admission, stage Ⅰ treatment consisted of thorough debridement and infection control based on bacterial culture and drug susceptibility test results. The lengths of bone defects were 6 cm and 22 cm, respectively. When the erythrocyte sedimentation rate and inflammatory markers returned to normal ranges, stage Ⅱ treatment (debridement and reconstruction with Zeta-focal bone lengthening) was performed. Distraction was initiated at 7 days after the second-stage operation. Docking of the bone segments was achieved at 11 and 40 days of distraction, respectively, and obvious mineralization in the distraction zones was observed at 65 and 104 days postoperatively. The external fixator was removed after radiographic evidence of cortical continuity at four sites was confirmed on anteroposterior and lateral X-ray films. The external fixation time was 112 and 357 days, respectively, and the external fixation indexes were 18.5 and 17.9 days/cm, respectively. Complications during the distraction period were observed. During follow-up, bone healing and functional recovery were evaluated with the Paley D score, the Association for the Study and Application of the Method of Ilizarov (ASAMI) score, the Lower Extremity Functional Scale (LEFS), and the American Orthopaedic Foot & Ankle Society (AOFAS) score. Results:Both patients completed the two-stage treatment. Their hospital stays were 21 and 16 days, respectively. Only mild pin-tract reactions occurred during the distraction period. Both patients were followed up for 18 months. At last follow-up, 2 patients achieved excellent functional results according to the ASAMI score, and bone healing was rated as excellent by the Paley D score. In 1 patient, the LEFS score was 76 and the AOFAS score was 95. The other patient was not scored because of knee arthrodesis. Conclusion:Under the prerequisites of strict infection control and individualized segmental design, Zeta-focal bone lengthening can achieve effective reconstruction of infectious bone defects and significantly reduce the external fixation time and the external fixation index.

ObjectiveTo compare autologous stem cell (SC) at different doses combined with core decompression (CD) versus CD alone for osteonecrosis of the femoral head (ONFH), using conversion to total hip arthroplasty (THA) as the primary outcome.MethodsPubMed, Embase, Cochrane Library, Web of Science, and CNKI were systematically searched (from inception to July 2025) to identify studies comparing different SC dosages (low dose: <1×10^7; medium dose: 1×10^7-10×10^8; high dose: >1×10^8). Conventional meta-analyses were performed using Review Manager 5.3, while network meta-analyses (NMA) were conducted with Stata 16.0. Treatment efficacy was ranked using SUCRA curves. Sensitivity analyses and funnel plots were applied to assess the robustness of the findings and potential publication bias.ResultsEighteen studies involving 1,192 patients were included. Compared with CD alone, evidence from conventional meta-analysis and network meta-analysis suggested that high-dose autologous stem cell therapy (>1×10^8 cells) combined with CD was associated with a lower risk of hip failure (conversion to THA) (OR = 0.24, 95% CI: 0.12 to 0.44). The high-dose group was also associated with a lower rate of femoral head collapse (OR = 0.24, 95% CI: 0.08 to 0.74) and lower VAS score (SMD = -1.93, 95% CI: -3.64 to -0.23). However, no statistically significant advantage of the high-dose group over the low- or medium-dose groups was observed, and no clear differences in incidence of adverse events (AEs) were detected across dose categories.ConclusionsPreliminary evidence suggests that, compared with CD alone, high-dose autologous stem cell therapy (>1×10^8 cells) combined with CD is associated with a lower risk of hip failure and a lower femoral head collapse rate, with additional improvements in pain in some comparisons. However, the certainty of evidence is limited by heterogeneity in study design, follow-up, and cell dose reporting. Future studies should emphasize standardized cell processing and intervention dosing to validate the dose–response relationship and establish the optimal clinical dosage.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record, identfier CRD420251154025.

Osteomyelitis (OM) is an inflammatory disease of bone infection and destruction characterized by dysregulation of bone homeostasis. Staphylococcus aureus (SA) has been reported to be the most common pathogen causing infectious OM. Recent studies have demonstrated that N6-methyladenosine (m6A) regulators are associated with the development of OM. However, the molecular mechanism of m6A modifications in OM remains unclear. Here, we investigated the function of methyltransferase-like 3 (METTL3)-mediated m6A modification in OM development. In this study, human bone mesenchymal stem cells (hBMSCs) were treated with staphylococcal protein A (SpA), a vital virulence factor of SA, to construct cell models of OM. Firstly, we found that METTL3 was upregulated in OM patients and SpA-induced hBMSCs, and SpA treatment suppressed osteogenic differentiation and induced oxidative stress and inflammatory injury in hBMSCs. Functional experiments showed that METTL3 knockdown alleviated the inhibition of osteogenic differentiation and the promotion of oxidative stress and inflammation in SpA-treated hBMSCs. Furthermore, METTL3-mediated m6A modification upregulated miR-320a expression by promoting pri-miR-320a maturation, and the mitigating effects of METTL3 knockdown on SpA-mediated osteogenic differentiation, oxidative stress and inflammatory responses can be reversed by miR-320 mimic. In addition, we demonstrated that phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) was a downstream target of miR-320a, upregulation of PIK3CA alleviated miR-320a-induced inhibition of osteogenic differentiation, and upregulation of oxidative stress and inflammatory responses during SpA infection. Finally, we found that silencing METTL3 alleviated OM development by regulating the miR-320a/PIK3CA axis. Taken together, our data demonstrated that the METTL3/m6A/miR-320a/PIK3CA axis regulated SpA-mediated osteogenic differentiation, oxidative stress, and inflammatory responses in OM, which may provide a new therapeutic strategy for OM patients.

ObjectivesThis study aimed to evaluate the biomechanical efficacy of a novel internal fixation system for the treatment of lumbar spondylolysis (LS). In addition, the changes in the mechanical performance of the proposed fixation construct during progressive compression were systematically investigated.MethodsA healthy 25-year-old male volunteer was recruited for lumbar spine CT data acquisition to construct and validate a nonlinear finite element model of the L4-S1 spinal segment (A); Based on this, models were established for L5 spondylolysis (B); L5 spondylolysis model with traditional internal fixation (C); L5 spondylolysis model with the pressurization process of the novel LS repair device fixation (D→E→F). For these six models, we constrained the lower surface of the S1 vertebral body while applying an axial compression force of 500 N and a moment load of 7.5 N m on the upper surface of the L4 vertebral body to simulate six motions of the lumbar spine. The performance of each finite element model was evaluated by comparing the range of motion (ROM), maximum displacement, and maximum pressure experienced by the lumbar spine under different motion conditions.ResultsCompared with Model C, Models D, E, and F exhibited a reduced ROM and maximum displacement under left axial rotation and right axial rotation conditions. Notably, compared with Model C, the novel internal fixation models consistently demonstrated a decreasing trend in the maximum stress on the intervertebral discs (IVD) and an increasing trend in the maximum stress on the articular cartilage and maximum stress and displacement of the bone graft. Moreover, The progressive pressurization (D→E→F) of the novel internal fixation model further enhanced stress transfer between the isthmic defect ends and the bone graft.ConclusionCompared with the conventional fixation model (Model C), the novel internal fixation models (Models D, E, F) provided superior spinal stability, more effectively restored physiological stress levels in the facet cartilage, and generated greater mechanical stimulation within the bone graft region. These findings suggest that the proposed fixation system may provide a more favorable biomechanical environment for pars defect healing and graft fusion.

Background Masquelet induced membrane surgery is a viable option for the reconstruction of extensive bone defects. This study aimed to comprehensively compare the clinical efficacy of 3D printed microporous tantalum prosthesis and autologous bone graft in the final stage of Masquelet induced membrane surgery during the treatment of lower extremity fracture-related infections(FRI) with large segmental bone defect. Methods We retrospectively analyzed the clinical data of 43 patients with large segmental bone defect caused by lower extremity FRI treated with Masquelet induced membrane surgery. Among these, 21 patients were implanted 3D printed microporous tantalum prosthesis (Prosthesis group), while 22 patients were implanted autologous bone graft (Autologous bone group) in the final-stage surgery. Follow-up was conducted for 12 months postoperatively. Clinical efficacy was evaluated using the Paley grade for bone defect healing, Visual analog scale (VAS), Lower extremity functional scale (LEFS), Fernandez-Esteve eschar score, and time to full weight-bearing. The clinical outcomes between the two treatment groups were compared. Results Postoperatively, the scores of VAS and LEFS significantly improved compared to preoperative values in both groups (all P < 0.001). Compared to the Autologous bone group, the Prosthesis group demonstrated significantly higher LEFS scores and Fernandez-Esteve eschar scores, along with a significantly shorter time to full weight-bearing (all P < 0.05). The complication rate was 19.0% (4/21) in the Prosthesis group and 9.1% (2/22) in the Autologous bone group; there was no statistically significant difference between the two groups (P > 0.05). Patients experiencing complications received effective and targeted interventions. Conclusion Both implants show remarkable efficacy in the reconstruction of large segmental bone defect caused by lower limb FRI. However, 3D printed microporous tantalum prosthesis exhibits certain advantages over the autologous bone graft in terms of limb function recovery, bone callus growth, and early weight-bearing. However, when using this technique, one should be vigilant about the risk of complications.

Although temporary intersegmental pedicle screw (TIPS) fixation improves stability of the treated segment, its isthmic fusion rate relative to that achieved with pedicle screw–vertebral plate hook (PSVPH) fixation remains unclear. Both PSVPH and TIPS are widely used in clinical practice. This study compared the clinical and radiological outcomes of PSVPH and TIPS for the treatment of lumbar spondylolysis. A retrospective analysis was conducted on 67 patients with lumbar spondylolysis who underwent surgical treatment with PSVPH (n = 35) or TIPS (n = 32) between October 2010 and October 2021. Clinical outcomes included incision length, operative time, intraoperative blood loss, visual analog scale (VAS) score, Oswestry Disability Index (ODI), and Japanese Orthopedic Association (JOA) score. Radiographic assessments comprised range of motion, disc height of stabilized and adjacent segments, adjacent segment degeneration, and bony fusion. Three-dimensional reconstruction of lumbar computed tomography was used to evaluate fusion, and Hounsfield units of the isthmic region were measured to assess bone healing during follow-up. Independent Student’s t-tests and chi-square tests were applied for intergroup comparisons. A total of 67 patients were included in the analysis. Incision length, operative time, and blood loss were all significantly reduced in the PSVPH group compared with the TIPS group (all P < 0.001). The 1-week postoperative VAS back pain score was significantly lower in the PSVPH group (P < 0.001). JOA scores at 3, 6, 12, and 24 months showed significantly greater improvement in the PSVPH group (P = 0.003, 0.034, < 0.001, and 0.001, respectively). At 24 months, the range of motion of the stabilized segment was significantly greater in the PSVPH group than in the TIPS group (P < 0.001). Postoperative intervertebral height of the stabilized segment in the PSVPH group at 1 week and 24 months was significantly lower than that in the TIPS group (P = 0.001; P < 0.013). Adjacent segment intervertebral height at 24 months was higher in the PSVPH group (P = 0.012), whereas adjacent segment range of motion was significantly lower (P = 0.012). The incidence of adjacent segment degeneration at 24 months was 2.9

Osteoclasts play an essential role as the main functional cells for bone resorption in osteomyelitis (OM). Staphylococcus aureus (SA), a prevalent pathogen causing bone infections, significantly contributes to OM by synthesizing substantial quantities of staphylococcal protein A (SpA). However, the potential mechanisms underlying the effects of SpA on osteoclastogenesis in OM need to be further explored. In our study, we found that SpA promoted the osteoclast differentiation and the inflammatory response in macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B ligand (RANKL)-treated THP-1 cells in a dose-dependent manner. Additionally, SpA-treated cells exhibited upregulation of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1). Silencing PVT1 reversed SpA-mediated inhibition of cell viability, and abolished SpA-induced promotion of osteoclast differentiation and the release of pro-inflammatory factors. Mechanistically, the upregulation of lncRNA PVT1 was regulated by methyltransferase-like 3 (METTL3)-mediated RNA N6-methyladenosine (m6A) modification. PVT1 increased the stability of hypoxia-inducible factor-1α (HIF-1α) by binding to its mRNA, thereby activating the HIF-1α/RANKL pathway and the pro-inflammatory NF-κB and MAPK signaling pathways. Furthermore, rescue experiments demonstrated that the silencing of METTL3-mediated upregulation of cell viability, along with the inhibition of osteoclast differentiation and inflammatory response, was reversed by overexpression of PVT1 in the presence of SpA. Meanwhile, the inhibitory effects induced by knockdown of PVT1 on osteoclast differentiation and inflammation were reversed by elevating HIF-1α. These data uncover that elevated expression of PVT1, regulated by METTL3-mediated m6A modification, activates the HIF-1α/RANKL pathway, thereby exacerbating osteoclast activation in SpA-induced OM.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by synovial inflammation and bone erosion, yet key immune-driven molecular regulators remain incompletely defined. This study aimed to identify differentially expressed genes (DEGs) in RA, explore their potential association with disease pathogenesis, and assess the potential of lymphocyte-specific protein tyrosine kinase (LCK) as a therapeutic target for RA. Bioinformatic analysis was conducted using three microarray datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A protein–protein interaction (PPI) network was constructed to identify hub genes, with further validation using clinical samples, an animal model, and in vitro experiments. The effect of LCK inhibition on RA progression was explored using a collagen-induced arthritis (CIA) rat model. A total of 115 DEGs were identified across three GEO datasets, with significant enrichment in immune-related pathways. PPI analysis highlighted LCK, GZMA, GZMB, CD2, LAG3, and CD247 as hub genes, with LCK markedly upregulated in RA synovium. LCK is a Src-family tyrosine kinase that phosphorylates the TCR/CD3 complex to initiate T-cell receptor signaling and drive CD4⁺ T-cell activation. Inhibition of LCK in CIA rats led to reduced CD4+ Tcell activation, osteoclast activity, and alleviated bone destruction. In vitro, LCK inhibition reduced CD4+ T-cell activation, suppressed osteoclast differentiation and inflammatory cytokine secretion. LCK may play an important role in RA by regulating with CD4+ T-cell activation and promoting osteoclast differentiation. Targeting LCK may represent a promising strategy to reduce inflammation and bone destruction in RA, suggesting its potential as a therapeutic target.

Staphylococcus aureus-induced bone infection is one of the thorny issues in clinical orthopedics, and understanding its detailed molecular regulatory mechanisms will help in seeking strategies. In this study, the differentially expressed genes in murine long bone osteocyte (MLO)-Y4 cells treated with or without Staphylococcus aureus were screened out through RNA sequencing, and microtubule actin crosslinking factor 1 (MACF1) was identified as one of the most significantly downregulated genes, which was validated by the subsequent RT-qPCR and Western blot. Then, Cellular functional assays showed that MACF1 overexpression markedly inhibited apoptosis and secretion of inflammatory mediators, but recovered cell viability and production of osteogenic markers in staphylococcal protein A (SPA) induced MLO-Y4 cells. Mechanistically, MACF1 mRNA was stabilized by N6 methyl adenosine (m6A) modification, and upregulated MACF1 inactivated the PI3K/AKT signaling in SPA-induced MLO-Y4 cells. To conclude, targeting m6A-methylated MACF1 ameliorates SPA-triggered inflammation, apoptosis and metabolic dysfunction in MLO-Y4 cells.

Background:Staphylococcus aureus (SA)-induced osteomyelitis causes refractory infected bone defects characterized by impaired osteogenesis and excessive inflammatory bone destruction. Pyroptosis has emerged as an important driver of infection-related tissue injury, but the upstream regulators in osteoblasts and effective local therapeutic strategies remain poorly defined. This study investigated the role of the MIF-CD74/PI3K/AKT axis in SA-mediated osteoblast dysfunction and evaluated the ISO-1 sustained-release hydrogel for repairing infected bone defects. Methods:MIF expression was examined in human osteomyelitis sample. Bone destruction, inflammation, and osteogenesis were compared between wild-type and Mif -/- mice using micro-CT, histology, ELISA, RT-qPCR, and immunohistochemistry. In vitro, SA-infected mouse bone marrow mesenchymal stem cells (mBMSCs) were used to assess proliferation, osteogenic differentiation, and pyroptosis, while MIF and CD74 were silenced with siRNA. RNA sequencing (RNA-seq) and co-immunoprecipitation (Co-IP) were employed to identify MIF downstream receptors and pathways, and PI3K/AKT involvement was verified using CD74 overexpression and the PI3K inhibitor LY294002. An injectable, photocrosslinkable ISO-1@β-CD/GelMA hydrogel was fabricated and characterized for structure, mechanics, and pH-responsive drug release, then implanted into rat femoral infected bone defects after debridement to evaluate bone regeneration and local inflammatory modulation. Results:MIF was markedly upregulated in human osteomyelitis and its genetic deletion in mice significantly attenuated SA-induced bone loss, preserved trabecular microarchitecture, enhanced osteogenic marker expression, and reduced local pro-inflammatory cytokines. SA infection suppressed mBMSC proliferation and osteogenic differentiation while activating NLRP3/ASC/GSDMD-dependent pyroptosis. MIF or CD74 knockdown partially restored osteogenesis and decreased inflammatory cytokine release and pyroptotic markers. RNA-seq and Co-IP identified CD74 as a key MIF receptor, with PI3K/AKT as a critical downstream pathway regulating osteoblast fate. The ISO-1@β-CD/GelMA hydrogel showed favorable injectability, mechanical stability, and sustained ISO-1 release, and significantly improved bone volume, microarchitecture, and inflammatory microenvironment in rat infected bone defects. Conclusion:SA-induced osteomyelitis disrupts bone homeostasis via the MIF-CD74/PI3K/AKT axis, thereby suppressing osteogenesis and promoting NLRP3/ASC/GSDMD-mediated osteoblast pyroptosis. Targeting MIF with an ISO-1 sustained-release hydrogel remodels the inflammatory and pyroptotic microenvironment, enhances osteogenic differentiation, and effectively promotes repair of infected bone defects, providing a promising translational platform for osteomyelitis-related bone regeneration.

Objective:The objective of the study was to evaluate the safety, feasibility, and radiographic outcomes of an intelligent robot-assisted fracture reduction (RAFR) system in the minimally invasive treatment of fresh, unstable pelvic ring injuries. Methods:In this single-center retrospective case series, 32 consecutive patients with unstable pelvic ring injuries (Tile type B or C) treated between August 2024 and April 2025 underwent minimally invasive closed reduction and internal fixation using the RAFR system. The system combines preoperative computed tomography (CT)-based three-dimensional reduction planning, intraoperative cone-beam CT (CBCT) registration, an optical tracking system, a table-mounted passive holding arm, and a robotic arm with dual force-position monitoring. Operative time, intraoperative blood loss, and fluoroscopic exposures were recorded. Postoperative CT was used to measure residual displacement, which was graded according to Matta's criteria, and the excellent-to-good rate was calculated. Functional outcomes were assessed using the Majeed score at the final follow-up. Results:All 32 procedures were completed using a closed, minimally invasive approach without conversion to open reduction. The median (IQR) operative time was 270 (225-311) min, blood loss was 150 (100-300) mL, and fluoroscopic exposures were 35 (30-45). The median residual displacement on CT was 4.0 (3.0-8.0) mm. According to Matta's criteria, 17 patients (53.1%) had excellent, 12 (37.5%) had good, and 3 (9.4%) had fair reductions, yielding an excellent-to-good rate of 90.6%. Two patients were lost to follow-up; among the remaining 30 patients, no major complications such as deep infection, implant failure, or iatrogenic neurovascular injury were observed, and the mean Majeed score was 76.7 ± 12.0. Conclusion:The RAFR system enabled closed reduction and percutaneous fixation of a heterogeneous cohort of unstable pelvic ring fractures with high rates of satisfactory reduction and favorable short-term functional recovery. These preliminary findings support the clinical feasibility and safety of robot-assisted closed reduction for unstable pelvic fractures and provide a basis for future comparative and multicenter studies.

Severe extremity injury results from high-energy trauma and causes extensive damage to multiple tissues. Such injuries directly threaten both limb viability and patient survival and remains a major challenge in trauma orthopaedics. The cornerstone of treatment is based on comprehensive assessment by a multidisciplinary team to guide evidence-based decisions on limb salvage. In repair and reconstruction strategies, the timing of soft-tissue coverage plays a critical role. Delayed primary flap coverage, performed 3-7 days after injury, has become the preferred approach. After repeated debridement to ensure a clean wound bed, this strategy improves flap survival and reduces infection risk. Fracture fixation requires dynamic decision-making. External fixators provide damage control and temporary stabilization and allow soft tissues to recover. Once conditions permit, conversion to internal fixation, such as intramedullary nails or plates to achieve stable fixation. Complex cases with severe contamination or infection require staged management. After thorough early debridement, local antibiotic delivery using antibiotic-loaded bone cement, such as vancomycin cement, can be applied. This is often combined with negative-pressure wound therapy, and external fixation may serve as definitive treatment. Large segmental bone defects can be managed using the induced membrane technique or bone transport. In addition, emerging strategies such as recombinant Staphylococcus aureus vaccines for infection prevention and three-dimensional-printed personalised implants for bone reconstruction show promising clinical potential.

INTRODUCTION:Chronic pain and high disability rates caused by osteoarthritis (OA) significantly impact quality of life. Programmed cell death (PCD) plays a crucial role in OA pathogenesis; however, a comprehensive analysis of PCD patterns in OA is lacking, limiting understanding of their potential role. METHODS:Batch transcriptomic data related to OA were obtained from the GEO database. Differential expression analysis based on 13 PCD patterns was performed to identify differentially expressed genes (DEGs). Unsupervised clustering algorithms were applied to define molecular subtypes associated with OA. The CIBERSORT algorithm was used to analyze the immune microenvironment and evaluate the immunological relevance of each cluster. Hub PCD-related DEGs were identified using a combination of machine learning algorithms, and an OA diagnostic model was constructed based on these hub genes. Single-cell RNA sequencing (scRNA-seq) dataset GSE169454 was used to classify OA chondrocytes into distinct cell clusters. The AddModuleScore function calculated PCD scores, allowing evaluation of hub-gene expression and PCD variation across clusters. Expression levels of ten hub PCD-related DEGs were further validated in OA cells and rat models. RESULTS:Differential expression analysis identified 61 PCD-related DEGs. Unsupervised clustering revealed two molecular subtypes of OA (cluster 1 and cluster 2), with immune-related pathways significantly enriched in cluster 1, including potential NK cell activation. Ten hub PCD-related DEGs were identified using three machine learning algorithms, leading to a highly effective diagnostic model (AUC = 0.993). Five distinct cell types were identified in OA chondrocytes, with higher PCD scores observed in OA samples and the HomC subgroup. Functional analysis indicated significant enrichment of the PI3K-AKT signaling pathway in high BINP3-expressing preHTCs, associated with extracellular matrix composition. mRNA and protein levels of the ten hub DEGs were confirmed in animal models. CONCLUSION:This multi-omics analysis of 13 PCD patterns provides a preliminary evaluation of the diagnostic and classification value of PCD-related genes in OA, highlighting potential biomarkers for clinical application.

Methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds are difficult to heal because of persistent bacterial colonization, prolonged inflammatory responses, and restricted tissue regeneration. In this study, a near-infrared (NIR)-responsive photocurable hydrogel system (ZPPE@PLHA) was developed for localized anti-infective therapy and tissue repair by incorporating ZnO/PDA/PEG/rhEGF composite nanostructures into a PLMA/HAMA matrix. The results showed that this hydrogel enabled sustained Zn²⁺ release and exhibited a stable mild photothermal effect (mPTT) under 808 nm NIR irradiation, with the temperature rising to approximately 48.6 °C within 10 min. In vitro experiments demonstrated that the ZPPE@PLHA hydrogel possessed intrinsic antibacterial activity co-mediated by Zn²⁺ and ε-PL, and that NIR irradiation further enhanced its inhibitory effects against MRSA and E. coli. Phenotypic observations and bacterial transcriptomic analyses indicated that this antibacterial effect was associated with membrane damage, metabolic disruption, and suppression of translation-related processes. Meanwhile, ZPPE@PLHA attenuated macrophage inflammatory activation and promoted M2-associated polarization in both classically activated and lipoteichoic acid (LTA)-stimulated macrophages, and enhanced endothelial cell migration and tube formation. In an MRSA-infected rat wound model, treatment with ZPPE@PLHA hydrogel combined with NIR significantly reduced the MRSA burden, improved the macrophage-mediated inflammatory microenvironment, and accelerated wound closure and angiogenesis, accompanied by increased EGFR expression and enhanced phosphorylation of PI3K, AKT, and ERK. By integrating antibacterial, immunomodulatory, and pro-regenerative activities, this hydrogel provides a full-process therapeutic strategy for the management of acute infected wounds.

Objective: With the accelerated aging of the population, aging has emerged as a major risk factor for osteoporosis (OP). This study aims to investigate the relationship and shared molecular mechanisms between OP and aging through various genetic approaches. Methods: Single-cell data from the peripheral blood of osteoporosis patients, aging individuals, and healthy controls were integrated to analyze characteristic changes in cell subpopulations. Differentially expressed genes (DEGs) were then identified within core subpopulations, and Mendelian Randomization (MR) analysis was employed to explore potential causal links between key genes and OP. Additionally, an OP model was established in rats, and mRNA levels of key genes were measured using RT-qPCR. Results: Through the integration, filtering, and analysis of scRNA-seq data, an increased proportion of CD4+ effector memory T (CD4+ TEM) cells were identified in OP and aging samples, marking them as a core subpopulation. Differential expression analysis identified 49 DEGs, and further analysis through Mendelian Randomization (MR) identified three key genes (KLRB1, NR4A2, and S100A4) significantly associated with OP. Notably, the upregulation of KLRB1 and S100A4 may enhance the interactions within T cells and with other cell subgroups. At the same time, the downregulation of NR4A2 could impede communication between T cells and other cell subpopulations. The RT-qPCR results indicated that NR4A2 was significantly downregulated in the OP group. Conclusion: This study conducted a comprehensive analysis of the potential link between OP and aging, identifying CD4+ TEM cells as the core cell subgroup in OP and aging samples. It further revealed the causal relationship between KLRB1, NR4A2, and S100A4 and the occurrence of OP. The upregulation of KLRB1 and S100A4 may contribute to OP pathogenesis by promoting interactions between CD4+ TEM cells and other cell subgroups, providing new insights for molecular targeting and immunotherapy of OP.

Bone tissue regeneration remains a major clinical challenge due to limitations of conventional grafts and synthetic scaffolds, including poor bioactivity and infection risks. To address these issues, silver-doped amorphous silica (Ag-aSiO2) nanocomposites were synthesized via a sol-gel method and systematically characterized. Structural and morphological features were confirmed using FTIR, XRD, SEM, and nitrogen adsorption analysis, revealing successful silver incorporation within the silica matrix while preserving its amorphous structure and high surface area. Antibacterial efficacy was evaluated against S. aureus using the disc diffusion assay, where 10 wt.% Ag-aSiO2 exhibited a clear inhibition zone (8.06 ± 0.04 mm), confirming strong antimicrobial activity absent in pure silica. Bioactivity studies in simulated body fluid (SBF) demonstrated robust hydroxyapatite (HA) formation, verified by SEM, EDX, and XRD, indicating excellent osteoconductive properties. The synergistic combination of amorphous silica’s high surface area and silver’s antibacterial action resulted in a multifunctional scaffold with dual benefits, which are effective infection control and enhanced mineralization for bone repair. These findings establish Ag-aSiO2 as a promising candidate for bone tissue engineering applications, integrating structural support, osteoconductivity, and antimicrobial protection. Future studies will focus on in vivo validation and clinical translation, with emphasis on optimizing silver release kinetics and long-term biocompatibility. KEY WORDS: Silver, Silica, Nanomaterials, Tissue engineering, Antimicrobial Bull. Chem. Soc. Ethiop. 2026, 40(11), 2473-2487 DOI: https://dx.doi.org/10.4314/bcse.v40i11.14

The overuse and improper application of antibiotics have significantly hastened the rise of antibiotic-resistant bacteria and reduced the efficacy of existing treatments. To address this escalating threat, the development of effective alternative strategies is urgently needed. Among these, reactive oxygen species (ROS)-based antimicrobial strategies have attracted widespread attention due to their non-invasive nature, low propensity for inducing resistance, and ability to eradicate drug-resistant bacteria and biofilms. This review provides a systematic analysis of nanomaterial-mediated ROS generation for antibacterial therapy. We first introduce the physicochemical properties of different ROS species and their fundamental antimicrobial mechanisms. Subsequently, we focus on three primary ROS-generating dynamic therapies: Photodynamic Therapy (PDT), Sonodynamic Therapy (SDT), and Chemodynamic Therapy (CDT). For each modality, we elaborate on the specific mechanisms of ROS generation mediated by nanomaterials and summarize recent advances in combating biofilm-associated and drug-resistant infections. Furthermore, we discuss the design principles of nanomaterials based on structure-activity relationships, highlighting how their properties govern ROS yield and selectivity. Finally, we address the key challenges and future directions in translating these ROS-based nanotherapies into clinical practice.

Objective:To elucidate the therapeutic challenges and recent advances in managing Garden type Ⅳ femoral neck fractures in young adults through the perspective of anatomical blood supply, identifying current limitations and proposing future research directions for optimizing clinical treatment strategies. Methods:A comprehensive review of recent domestic and international literature on Garden type Ⅳ femoral neck fractures in young adults was conducted, focusing on the anatomical basis of femoral neck vascularization, innovations in internal fixation techniques, vascular reconstruction methods, and applications of adjunct technologies. Results:The treatment of Garden type Ⅳ femoral neck fractures in young adults has evolved from internal fixation toward an integrated biomechanical and biological approach. The distinct anatomy of the femoral neck and the vulnerability of femoral head perfusion render the management of Garden type Ⅳ fractures particularly challenging in young adults. Enhanced internal fixation systems have significantly improved stability through optimized biomechanical configurations. Vascularized (or muscle-pedicle) bone grafting offers an effective biological reconstruction strategy for high-risk patients. Conclusion:Individualized comprehensive treatment, grounded in the understanding of femoral neck vascular anatomy, is crucial for improving outcomes. Future efforts should integrate intelligent surgical planning and biological therapeutics to further enhance therapeutic efficacy.