Osteoarthritis (OA) is a prevalent disease of the whole joint, in which synovial hyperplasia, inflammation, and fibrosis are important pathological manifestations. Melatonin (MT) possesses diverse biological activities and has shown promise in mitigating cartilage degradation in OA. However, further research is required to clarify MT's effects and mechanisms on OA synovium. Fibroblast-like synoviocytes (FLSs) were isolated and identified by immunofluorescence. Cell counting kit-8, EdU, flow cytometry, transwell, and wound healing assays were employed to assess the proliferation, DNA replication, cell cycle, apoptosis, and migration of FLSs. TGF-β1 was used to induce inflammation and fibrosis in FLSs. Protein and mRNA expression levels were evaluated using Western blot, enzyme-linked immunosorbent assay, immunofluorescence, and real-time quantitative PCR. Additionally, an OA rabbit model was established, and the pathological changes of synovium, synovial fluid, cartilage, and subchondral bone were investigated to assess the in vivo effects of MT on OA. The proliferation, DNA replication, and expression of proliferating cell nuclear antigen (PCNA) and c-Myc of FLSs were inhibited by MT intervention. MT arrested the cell cycle by inhibiting the expression of cyclin D1 and cyclin E1, induced apoptosis via down-regulating B-cell lymphoma-2 (Bcl-2) and up-regulating Bcl-2 associated X (Bax), and suppressed the migration by impairing vimentin expression in FLSs. Mechanistically, MT exerted these effects by regulating the Hippo/YAP and PI3K/AKT pathways. Moreover, MT ameliorated synovial hyperplasia, inflammation, fibrosis, and pathological changes in synovial fluid, as well as the destruction of cartilage and bone in the OA rabbit model. Our findings indicate that MT alleviates synovial pathological changes and delays OA progression, which is related to its ability to suppress aberrant FLS functions.

Accurate measurement of acetabular cup orientation after total hip arthroplasty is essential, but postoperative CT relies on subjective, error-prone manual measurement. Robot-assisted surgery provides intraoperative cup-orientation measurements but is costly and not widely available. We aimed to develop and evaluate a deep-learning model measuring cup orientation on postoperative CT, using robotic navigation values as reference standard. This secondary analysis of a randomized trial (ChiCTR2200060115) analyzed 94 hips with robotic intraoperative angle measurements and postoperative CT (May 2023 to May 2024). A VGG16-based U-Net segmented key anatomical structures into three-dimensional point clouds. Three measurement pathways were compared: manual annotation, machine learning, and deep learning. The optimal model was integrated into a graphical user interface. Ninety-four hips (mean age, 57.0 years ± 9.5 [standard deviation]; 62 men) were evaluated using 27,821 CT images. The best model (PointNet++) achieved mean absolute errors of 4.48° (anteversion) and 3.89° (inclination), compared with 4.08°/ 5.52° for machine learning and 8.91°/ 8.70° for manual measurement, significantly outperforming manual measurement (both p < 0.05). Exploratory full-cohort Lewinnek classification was correct in 81/94 hips versus 57/94 with manual measurement; in internal validation, 71

ABSTRACT Mechanical cues shape bone regeneration, but treatments for delayed union, nonunion, and mechanically mismatched repair often still treat them as static constraints. In this review, we use mechanical intelligence to describe the time‐dependent capacity of biomaterials, cells, and therapeutic devices to store, transform, and transmit mechanical history during repair. Two forms of memory are central to this view. Scaffolds and implants can preserve or release previous mechanical states through relaxation, residual stress, shape recovery, evolving stiffness, and architecture, whereas cells can carry earlier stiffness or loading exposure into later mechanotransduction, lineage commitment, and niche remodeling. The key question is when these two forms of memory meet during healing, from cell recruitment and matrix formation to callus maturation, load sharing, and rehabilitation. Coupling material and cellular memory may help match scaffold mechanics to cellular decision windows and tissue competence, support osteogenesis, reduce maladaptive responses such as stress shielding or fibrosis, and guide stage‐specific scaffolds, adaptive fixation, sensing‐assisted modelling, and mechanically timed rehabilitation for personalized bone repair.

Objective:To summarize 10-year orthopedic experiences in the management of hemophilic pseudotumor and to discuss an individualized treatment strategy centered on surgery. Methods:The clinical data of 8 patients with hemophilic pseudotumor between June 2015 and May 2025 were retrospectively analyzed. All patients were male, aged 15-37 years, with a mean age of 27.3 years. Seven patients had hemophilia type A and 1 had hemophilia type B; all had severe hemophilia and no detectable inhibitor. The disease duration ranged from 2 months to 12 years, with a mean of 2.5 years. There were 7 soft-tissue pseudotumors and 1 osseous pseudotumor. Lesions involved the lower leg in 3 cases, the thigh in 1, the hip in 1, both the hip and thigh in 2, and both the knee and thigh in 1. Pseudotumor size ranged from 5 cm×5 cm×4 cm to 32 cm×19 cm×15 cm. Treatment modalities included conservative treatment in 1 case, pseudotumor excision in 5 cases, and transfemoral amputation in 2 cases. Perioperative factor replacement was administered according to hemophilia type and factor activity, followed by wound care, anti-infective treatment when needed, drainage management, and rehabilitation. Results:For 7 patients undergoing surgery, the operation time was 60-120 minutes (mean, 88.6 minutes), and the intraoperative blood loss was 150-700 mL (mean, 342.9 mL). Six patients received coagulation factor Ⅷ at doses of 25 400-40 000 U (mean, 32 600 U); 1 patient received coagulation factor Ⅸ at a dose of 35 000 U; the length of hospital stay was 15-30 days (mean, 22.1 days). All patients were followed up 2-10 years (mean, 3.9 years.). One patient developed a superficial wound infection, which resolved after sensitive antibiotics and dressing changes. One patient with a lower-leg soft-tissue pseudotumor healed after conservative treatment and had no recurrence. Among the 5 patients treated with pseudotumor excision, 1 patient with an osseous pseudotumor achieved satisfactory wound and bone healing after pseudotumor resection, allogeneic bone grafting, and internal fixation; 3 patients with soft-tissue pseudotumors had no recurrence during follow-up; and 1 patient with a giant hip soft-tissue pseudotumor developed recurrence with ulceration and massive bleeding at 2 years after surgery and eventually died after unsuccessful rescue at another hospital. The 2 patients who underwent amputation achieved wound healing and returned to daily life after prosthetic fitting and rehabilitation. Conclusion:Surgery remains the main treatment for hemophilic pseudotumors that fail conservative treatment or present with progressive enlargement, ulceration and infection, or compression of vital structures. Adequate perioperative factor coverage, precise preoperative imaging, complete excision whenever feasible, and meticulous elimination of dead space are essential to reduce complications and recurrence.

Objective:To investigate effect of coronal plane alignment of the knee (CPAK) phenotype alteration on patient-reported outcome measures (PROMs) and functional outcomes in patients undergoing robot-assisted total knee arthroplasty (RA-TKA). Methods:The clinical data of 108 patients who underwent unilateral RA-TKA between December 2024 and June 2025 and met the inclusion criteria were retrospectively analyzed. The cohort included 34 males and 74 females, with an average age of 68.8 years (range, 54-83 years). General data including age, gender, body mass index (BMI), and operative side were collected. PROMs included the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), Knee Society Score (KSS), and Forgotten Joint Score-12 (FJS-12). Functional outcomes included range of motion (ROM) and angle of knee extension lag. Based on full-length lower extremity X-ray films, the mechanical lateral distal femoral angle (mLDFA) and mechanical medial proximal tibial angle (mMPTA) were measured, and the arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) were calculated. The CPAK phenotype was determined according to the classification proposed by MacDessi et al. Patients were grouped into a CPAK consistent group and a CPAK changed group based on pre- and post-operative CPAK phenotypes, and the PROMs, functional outcomes, and radiographic parameters were compared. Multiple linear regression analysis was used to examine the independent association between CPAK phenotype change and the improvement in WOMAC scores. Results:Among the 108 patients, the CPAK phenotype remained unchanged in 70 cases (64.8%, CPAK consistent group) and changed in 38 cases (35.2%, CPAK changed group). There was no significant difference between the two groups in age, gender, BMI, operative side, or preoperative WOMAC score, KSS score, ROM, and aHKA ( P>0.05), whereas preoperative JLO showed a significant difference between groups ( P<0.05). Univariate analysis demonstrated significant differences between groups at 3 months postoperatively in WOMAC, KSS, and FJS-12 scores, as well as in the changes of WOMAC score, KSS score, and ROM ( P<0.05); moreover, the improvements in these parameters were superior in the consistent group compared to the changed group. There was no significant difference in postoperative ROM, angle of knee extension lag, mLDFA, mMPTA, JLO, aHKA, and the change of aHKA between groups ( P>0.05). Multiple linear regression analysis revealed that CPAK phenotype change was a risk factor for improvement in WOMAC scores at short-term stage ( P<0.05). Conclusion:Preservation of the preoperative CPAK phenotype after RA-TKA is associated with superior improvement in PROMs at short-term stage.

Background:Polyetheretherketone (PEEK) is a promising orthopedic implant material due to its bone-matched elastic modulus and radiolucency. However, its clinical application is limited by biological inertness and lack of antibacterial activity, which predispose to implant-associated infection (IAI) and poor osseointegration. This study developed a multifunctional coating on sulfonated PEEK (SPEEK) via polydopamine (PDA)-mediated co-delivery of simvastatin-loaded ZIF-8 nanoparticles (SIM@ZIF-8) and moxifloxacin (MOX) to address these limitations. Methods:A time-programmed release coating was fabricated on SPEEK by embedding SIM@ZIF-8 within a PDA layer and surface-loading MOX onto the surface. The coating's physicochemical properties, drug release profiles, biocompatibility, antibacterial activity, and osteogenic capacity were evaluated in vitro. Antibacterial efficacy and osseointegration were further assessed in vivo using rat subcutaneous infection and rabbit femoral defect models. Results:Release profiles revealed that MOX exhibited burst release within 24 h, whereas SIM quickly reached therapeutic concentrations during the initial phase and was slowly released over five weeks, while Zn2+ from ZIF-8 was released synchronously with SIM. In vitro antimicrobial assays showed that the synergistic release of MOX and SIM exhibited potent antibacterial activity against Staphylococcus aureus and Escherichia coli, providing sustained inhibition of Staphylococcus aureus biofilms. The coating also promoted MC3T3-E1 cell adhesion, spreading, and osteogenic differentiation, as indicated by upregulated osteogenic markers (Runx2, OCN, OPN, COL1A1), enhanced matrix mineralization, and increased BMP-2 expression. In rat models, bacterial colonization on the coated surface and residual bacteria in tissues were significantly reduced. In rabbit femoral defects, sustained co-release of SIM and Zn2+ accelerated new bone formation and improved osseointegration, confirmed by micro-CT, double fluorescence labeling, and histological analysis. Conclusion:This study presents a novel bioactive PEEK implant coating integrating antibacterial and osteogenic functions through a MOX/SIM@ZIF-8/PDA system. The strategy effectively combats IAI and enhances osseointegration, offering potential for clinical orthopedic applications.

Robot-assisted total hip arthroplasty (THA) improves component-placement accuracy but lengthens the operative time, an established risk factor for perioperative complications. Whether this additional operative time increases perioperative trauma has not been formally tested, particularly where the robot-assisted THA procedure is substantially longer. This was a post hoc analysis of a prospective, multicenter randomized controlled trial comparing seven-axis robot-assisted and conventional THA at 3 centers. The modified intention-to-treat population comprised 99 operated patients (47 in the robot-assisted THA group and 52 in the conventional THA group). We compared operative time, blood loss, intraoperative transfusion, postoperative day-7 C-reactive protein and composite cellular-immune ratios, and adverse events, with all comparisons adjusted for study center. Exploratory mediation estimated the model-based indirect association between treatment assignment and blood loss through operative time. Robot-assisted THA took substantially longer than the conventional procedure (median 150 vs. 106 min; center-adjusted difference 34.8 min; P < 0.001), yet no statistically significant between-group differences were detected in blood loss, intraoperative transfusion, postoperative day-7 inflammatory markers, or adverse events. Exploratory mediation identified an indirect association through operative time (+ 97.8 mL, bootstrap 95

BACKGROUND:Polynucleotide phosphorylase 1 (PNPT1) functions as a crucial mitochondrial enzyme; nevertheless, its potential genetic correlation with osteoporosis and its specific regulatory impact on osteoclastogenesis remain to be elucidated. METHODS:We executed a two-sample Mendelian randomization (MR) strategy to interrogate the causal link connecting PNPT1 expression to osteoporosis risk. For in vivo substantiation, we utilized both an ovariectomized (OVX) murine model and an adeno-associated virus (AAV)-driven overexpression system. Extensive in vitro assays employing RANKL-stimulated RAW264.7 macrophages were conducted to evaluate osteoclast differentiation, mitochondrial dynamics, autophagic flux, and intracellular oxidative stress through molecular and morphological analyses. RESULTS:MR evaluations pinpointed genetically predicted elevated PNPT1 expression as a potential genetic risk factor for osteoporosis. In vivo observations revealed a significant surge of PNPT1 within the osteoclast precursors of OVX subjects. In vitro, the ectopic overexpression of PNPT1 significantly enhanced osteoclastogenesis and bone degradation while simultaneously triggering severe mitochondrial depolarization alongside the accumulation of reactive oxygen species (ROS). On the contrary, targeted Pnpt1 silencing markedly suppressed osteoclast maturation. Mechanistic probes demonstrated that PNPT1 disrupted autophagic flux, marked by p62 accumulation. Notably, even with a compensatory transcriptional rise in Nrf2 mRNA, PNPT1 overexpression provoked a marked downregulation of Nrf2 and xCT proteins, suggesting a potent post-transcriptional suppression of the cellular antioxidant shield. This uncoupling invariably precipitated sub-lethal lipid peroxidation that amplifies osteoclastogenic signaling. Concordantly, AAV-mediated systemic PNPT1 amplification aggravated trabecular bone deterioration in vivo. CONCLUSION:Guided by our MR findings and validated through our functional models, PNPT1 emerges as a potential genetic risk factor for osteoporosis. By inciting mitochondrial damage, provoking ROS buildup, and decoupling the protective autophagy-Nrf2/xCT axis, PNPT1 promotes osteoclastogenesis, thereby introducing a promising immunopharmacological target for restraining pathological bone resorption.

ABSTRACT Background Cardiometabolic Multimorbidity (CMM) is defined as the co‐occurrence of two or more conditions among heart disease, diabetes mellitus, stroke, and hypertension. Previous studies have shown associations between cardiometabolic diseases and fragility fractures; however, the relationship between CMM and hip fractures remains unclear in the Chinese population. This study therefore aims to investigate this association in a Chinese cohort to inform fracture prevention strategies. Methods This prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS) collected from 2011 to 2020. Participants from the 2011 baseline survey cohort were initially included. Subsequently, individuals were sequentially excluded if they were under 45 years of age, had incomplete baseline CMM information, had a history of hip fracture, lost to follow‐up, or had missing data on confounders. Kaplan–Meier survival analysis, Cox proportional hazards regression, subgroup analyses, and sensitivity analyses were performed to evaluate the association between CMM and the risk of hip fracture. Results A total of 6314 participants aged 45 years and older were included, of whom 544 had CMM. Over a 9‐year follow‐up period, 287 incident hip fractures (4.55%) were identified. Among these, 36 participants had been diagnosed with CMM at baseline, whereas 251 had not. The incidence of hip fracture was significantly higher in participants with CMM than in those without CMM (13% vs. 8%, p = 0.015). After full adjustment for confounders, multivariable Cox regression showed that CMM was associated with a 70% increased risk of hip fracture (HR = 1.70, 95% CI: 1.318–2.47; p = 0.005). Subgroup analyses indicated that age and history of falls were significant effect modifiers. The association between CMM and hip fracture was more pronounced in participants under 60 years old (P for interaction = 0.048) and those with a history of falls (P for interaction = 0.014). Conclusion These findings suggest that CMM increases the risk of hip fracture, particularly among relatively younger individuals and those with a history of falls.

Polyetheretherketone (PEEK) is an attractive orthopedic implant material due to its bone-matched elastic modulus, chemical stability, and low toxicity. However, its bioinertness and poor osseointegration limit its clinical application, activating inflammatory responses and causing fibrous encapsulation. To address these issues, we designed a polydopamine (PDA)-assisted coating on sulfonated PEEK (SP) that released cytokines and drugs to regulate the immune response and promote osteogenesis. We constructed a bio-self-assembled apatite (Ap) layer via simulated body fluid (SBF) immersion, followed by PDA-mediated deposition of dexamethasone (DEX)-loaded zeolitic imidazolate framework-8 (ZIF-8) nanoparticles and the surface adsorption of interleukin-4 (IL-4). The SP-Ap-DEX@ZIF-8-PDA-IL4 construct released IL-4 within 7 days and DEX within 28 days, while releasing calcium and zinc ions. The coating promoted the adhesion, spreading, and osteogenic differentiation of MC3T3-E1 cells. The coating polarized macrophages toward an anti-inflammatory M2 phenotype, suppressing pro-inflammatory cytokines while increasing anti-inflammatory cytokines. Results showed that macrophageconditioned medium promoted osteodifferentiation, and RNA sequencing (RNA-Seq) indicated that the coating inhibited pro-inflammatory NF-kappa B signaling while activating the cGMP-PKG pathway. The rat air pouch model demonstrated that the coating inhibited inflammation and reduced fibrous capsule formation by promoting M2 macrophage polarization and inhibiting M1 polarization. An in vivo study using a rabbit femoral defect model showed that the coating accelerated new bone deposition and improved osseointegration. This study presents a temporal release strategy that integrates early immunomodulation with long-term osteogenic stimulation of PEEK implants, offering potential for bioactive orthopedic implants.

Osteoporotic bone defects (OBD) are characterized by a persistent inflammatory imbalance and dysregulated osteoimmune responses, creating a pathological microenvironment that severely compromises the efficacy of conventional biomaterial-based therapies. Herein, we report a structure-evolving bone bioadhesive designed for temporally programmed osteoimmune modulation to achieve functional OBD regeneration. This bioadhesive is engineered by covalently grafting alendronate (ALN) onto a bovine bone-derived gelatin backbone to form ALN-grafted gelatin (Gel-ALN), which is subsequently cross-linked with bis-arm poly (ethylene glycol) succinimidyl glutarate (Bi-PEG-SG). The subsequent incorporation of Sr2+ via reversible coordination with the bisphosphonate groups of ALN creates the poly(ethylene glycol)-gelatin/strontium-alendronate (PG/Sr-ALN) dynamic organic–inorganic hybrid network. In the early inflammation-dominated acidic microenvironment, the pH-responsive dissociation of Sr2+-ALN coordination bonds triggers the localized release of Sr2+, which effectively suppresses the PI3K-Akt and NF-κB signaling pathways to drive the polarization of macrophage toward a pro-regenerative M2 phenotype. Concurrently, as the gelatin matrix undergoes programmed degradation, the progressive exposure of covalently integrated ALN ensures sustained inhibition of osteoclastogenesis while simultaneously bolstering osteogenic differentiation. By leveraging the synergistic interplay between coordination dynamics and network erosion, PG/Sr-ALN autonomously realizes a stage-specific bioactivity evolution that rehabilitates the osteoimmune niche. This study not only identifies a structure-evolution-driven strategy for precise temporal modulation of the osteoimmune environemnt but also establishes a practical framework for the development of multifunctional repairing scaffolds aimed at the osteoporotic bone regeneration.

The homogeneous structure with single function is inadequate to meet the multifunctional demands of different regions. Herein, we proposed a multi-material polyether-ether-ketone (PEEK) matrix heterogeneous architecture driven by diversified functions. The lateral side of femoral prosthesis was incorporated highly oriented short carbon fiber (SCF) to improve biotribological properties, the inner side was incorporated hydroxyapatite (HA) and porous structure for rapid ingrowth of bone tissue. The wear volume of 20SCF/40HA/PEEK decreased to 1.54 +/- 0.45 mm3, and showed a considerable improvement in wear resistance by 66.00 % compared to that of the PEEK. The bone growth volume increased to 27.96 %, showing significant biological fixation effect. The proposed strategy for heterogeneous structure with multifunctionality showcases great application prospects in the field of joint prostheses.

BACKGROUND:Glucocorticoid (GC) overuse is the main cause of osteonecrosis of the femoral head (ONFH). The dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays an important role in ONFH pathogenesis. Physiological concentrations of GCs can induce the osteogenic differentiation of BMSCs; however, intervention with high concentrations of GC may lead to changes in aging and autophagy in certain cell types. METHODS:We generated an ONFH mouse model by injecting C57BL/6 J mice with MPS. BMSCs were harvested from the femora and tibiae of mice and were analyzed for osteogenesis, adipogenesis, senescence, and cell proliferation. In vitro, BMSCs were treated with different concentrations of GC for 48 h, followed by functional analyses to identify differentially expressed genes (DEGs) associated with ONFH. Additionally, various bioinformatics analyses were performed to identify differentially expressed genes in ONFH. RESULTS:BMSCs from ONFH mice showed signs of aging, as indicated by increased SA-β-gal positive cells (4.4-fold) and upregulated p53 (2.6-fold) and p21 (2.0-fold) protein expression. It is also accompanied by changes in osteogenic/lipogenic differentiation ability. Bioinformatics analysis further verified these findings. High-dose GC stimulation significantly induced cellular senescence of BMSCs, as indicated by an increase in SA-β-gal positive cells (6.2-fold) and a decrease in autophagy levels. GC stimulation changes the differentiation fate of BMSCs. CONCLUSIONS:Our results indicated that GC-induced ONFH was associated with changes in aging and autophagy in BMSCs. GC not only directly affected the osteogenic differentiation of BMSCs but also indirectly affected their differentiation fate through aging and autophagy changes.

BACKGROUND:Patients often report leg-length discrepancy (LLD) after total hip arthroplasty (THA). The factors behind self-reported LLD (sLLD) are unclear. Robot-assisted THA (RA-THA) offers improved precision, but its effect on sLLD has not been well studied. This study aimed to assess RA-THA's benefits in reducing sLLD and identify impacting factors. METHODS:Patients who underwent RA-THA or conventional THA (CON-THA) at three Chinese hospitals were reviewed. Propensity score matching was used to match the RA-THA and CON-THA groups by preoperative data. Initially, 215 patients were enrolled; nine were excluded. The RA-THA group had 102 patients, and the CON-THA group had 104. After propensity score matching, 74 patients remained in each group. Postoperative outcomes, including imaging data, clinical scores, and sLLD, were compared. Patients were categorized by whether the measured LLD (mLLD) postsurgery was less than 10 mm. Disparities in data and surgical methods were compared. Univariate and multivariate logistic regression analyses identified sLLD predictors. RESULTS:The RA-THA group showed better postoperative mLLD, cup anteversion, inclination, and offset discrepancy, but no significant differences in sLLD at 3 years. The RA-THA percentage was higher in the mild LLD group (59.4%) and lower in the severe LLD group (32.7%). Patients who had mild LLD had a lower proportion of sLLD at 3 years. Logistic regression identified preoperative mLLD, preoperative Harris Hip Score (HHS), postoperative mLLD, and postoperative HHS as significant predictors of sLLD. CONCLUSIONS:The RA-THA may not significantly reduce sLLD. Key predictors of sLLD included preoperative mLLD, preoperative HHS, postoperative mLLD, and postoperative HHS, highlighting the need for thorough preoperative assessment and patient education for better outcomes and satisfaction.

Managing large, critical-sized bone defects poses a complex challenge, especially when autografts are impractical due to their size and limited availability. In such situations, the development of synthetic bone implants becomes crucial. These implants can be carefully designed and manufactured as potential bone substitutes, offering controlled parameters such as porosity, hardness, and osteogenic cues. In this study, we employed digital light processing (DLP) technology to construct an alumina ceramic scaffold featuring a triply periodic minimal surface (TPMS) structure for bone transplantation. The scaffold was filled with type I collagen to enhance cell infiltration [1], thereby increasing the total surface area. In addition, type I collagen is a carrier for both bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA). Using a clinically relevant rabbit cranium defect model, the scaffold underwent in vivo assessment for its functionality in repairing critical-sized bone defect (approximately 8 mm). Four groups of animal experiments were carried out including the control group, the gyroid scaffold group, the type I collagen-loaded scaffold group, and the bioactive factor-functionalized scaffold group. Our animal-based study results revealed that the gyroid scaffold, functionalized with bioactive molecules, provided a conductive surface for promoting increased bone formation and enhancing the healing process in critical-sized long bone and cranium defects. These findings offer preclinical evidence, supporting the use of a TPMS structure composite scaffold and present compelling support for its application as an advanced synthetic bone substitute in the future.

Osteonecrosis of the femoral head (ONFH) is an orthopaedic disease with multifaceted pathogenesis. The role of long noncoding RNA (lncRNA) taurine-up-regulated gene 1 (TUG1) in ONFH remains unexplored. Thus, lncRNA expression profiles in subchondral bone from patients with ONFH and healthy controls were analyzed using microarray analysis, RT-qPCR, and bioinformatics. To evaluate the effect of TUG1 on osteogenic differentiation, TUG1 was overexpressed or knocked down in human bone marrow mesenchymal stem cells (hBMSCs), assessed via quantitative RT-PCR, Western blot analysis, and staining assays. In vivo, TUG1 was knocked down using adeno-associated viruses in a rat ONFH model. Micro-computed tomography, histology, enzyme-linked immunosorbent assay, quantitative RT-PCR, and immunohistochemistry were used to assess bone mass and osteogenic markers. TUG1 was significantly down-regulated in ONFH subchondral bone. Overexpression of TUG1 in hBMSCs up-regulated osteogenesis-related genes and proteins (runt-related transcription factor 2, osteopontin, osteocalcin, collagen type I alpha 1 chain, bone morphogenetic protein 2, and β-catenin), enhanced alkaline phosphatase activity, and increased mineralization. Conversely, TUG1 knockdown reduced these markers. In vivo, TUG1 knockdown disrupted bone microstructure and decreased osteogenic marker expression in the femoral head. This study revealed that TUG1 is down-regulated in ONFH subchondral bone, leading to osteogenic dysfunction through the Wnt/β-catenin pathway. It provided a better understanding of lncRNA's regulatory role in local osteonecrosis and offered new insights into ONFH pathogenesis. This study provides a reference for future research and treatment strategies.

The present study aimed to compare the efficacy and safety of loxoprofen sodium cataplasm (LSC) with those of flurbiprofen cataplasm (FPC) in osteoarthritis (OA) treatment. In this multicenter, randomized controlled trial, subjects meeting the inclusion and exclusion criteria were randomly assigned to the two treatment groups. According to the manufacturer's instructions, the first group received LSC once daily, with the application of one patch per area for 2 weeks, whereas the second group received FPC twice daily, with the application of one patch per area for 2 weeks. The treatment response was evaluated based on the Visual Analog Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, Lysholm score and adverse events for 296 patients enrolled across three subcenters, with 192 patients in the LSC group and 104 patients in the FPC group. The treatment effectiveness rates, based on the VAS, WOMAC global and Lysholm scores, were 74.46, 61.41 and 85.25%, respectively, for the LSC group and 43.14, 31.37 and 66.67%, respectively, for the FPC group. Regardless of the effectiveness criterion used, the LSC group exhibited a superior treatment effectiveness rate compared with the FPC group. After 2 weeks of treatment, OA symptoms improved in both groups, with the LSC group exhibiting lower VAS (P<0.05) and WOMAC global scores (comprising pain, stiffness and physical function scores) compared with the FPC group (P<0.05), while the Lysholm score was higher in the LSC group compared with the FPC group (P<0.05). The FPC group experienced more general adverse events (P>0.05) and dressing shedding (P<0.05) compared with the LSC group, whereas the LSC group had more specific adverse events (such as skin itching, fever and allergy) compared with the FPC group (P>0.05). The results suggested that compared with FPC, LSC exhibited higher short-term efficacy and a consistent safety profile. The present study was registered at Chinese Clinical Trial Register (chictr.org.cn; ChiCTR2300072504; date of registration, June 15, 2023).

Despite its biomechanical advantages, polyetheretherketone (PEEK) exhibits bioinertness and pro-inflammatory responses, which limit its efficacy in bone-defect repair. Therefore, we aimed to engineer three-dimensionalprinted PEEK scaffolds functionalized with a polydopamine (PDA)-assisted nano-calcium silicate (n-CS)/interleukin-4 (IL-4) coating (PEEK/PCS/IL-4) to synergistically modulate immune responses and osteogenesis to overcome the challenges associated with PEEK. The scaffolds were fabricated through fused deposition modeling under optimized conditions and subsequently subjected to sequential surface functionalization involving PDAmediated n-CS immobilization followed by IL-4 impregnation. In vitro, the PEEK/PCS/IL-4 scaffolds significantly enhanced human bone marrow mesenchymal stem cell (hBMSCs) spreading, alkaline phosphatase activity, mineralization, and osteogenic gene expression compared with the controls. The scaffolds also promoted human umbilical vein endothelial cell migration and tube formation, suggesting potent pro-angiogenic effects. RAW264.7 macrophages cultured on PEEK/PCS/IL-4 exhibited M2 polarization, elevated transforming growth factor-beta 1 (TGF beta 1), and suppressed tumor necrotic factor-alpha levels (TNF alpha), which correlated with the noncanonical NF-kappa B pathway inhibition. The conditioned medium from PEEK/PCS/IL-4-primed macrophages further amplified hBMSCs osteogenesis, confirming immune-osteogenic coupling. In vivo, PEEK/PCS/IL-4 scaffolds reduced fibrous encapsulation and enhanced M2 macrophage polarization in a rat subcutaneous implantation model. In rabbit femoral defects, micro-CT, confocal laser scanning microscopy, histology, and biomechanical testing results revealed that the PEEK/PCS/IL-4 scaffolds exhibited enhanced osteogenesis and superior osseointegration. This study pioneers an immuno-engineering approach to transform bioinert PEEK into a bioactive platform, leveraging n-CS/IL-4 coatings to harmonize immune homeostasis, bone regeneration, and revascularization, offering a transformative strategy for bone defect repair.

Objective: This study aimed to elucidate the regulatory mechanisms of the long intergenic non-protein coding RNA 02381 (LINC02381)/microRNA-let-7g-5p (let-7g-5p)/thrombospondin 1 (THBS1) signaling axis in osteosarcoma (OS). Methods: The expression levels of LINC02381, let-7g-5p, and THBS1 were quantified in OS and adjacent normal tissues via reverse transcription quantitative polymerase chain reaction. Their correlations with clinicopathological features were analyzed. Expression patterns were further validated in OS cell lines (143B, U-2OS, Saos-2, MNNG-HOS, MG-63) and normal osteoblast cell line hFOB1.19. The molecular interaction between LINC02381 and let-7g-5p and the targeting relationship of let-7g-5p with THBS1 were verified via dual-luciferase reporter and RNA pull-down assays. Functional effects were assessed using cell counting kit-8, colony formation, Transwell migration, and xenograft tumor models. Results: Compared to adjacent normal tissues, LINC02381 and THBS1 were upregulated in OS tissues (fold change > 3.0, p < 0.001), while let-7g-5p was downregulated (fold change ≈ 0.038, p < 0.001). Similar expression trends were observed in U-2OS cells. Knockdown of LINC02381 or overexpression of let-7g-5p reduced cell proliferation, colony formation, migration, THBS1 expression, and tumor volume (p < 0.001). These inhibitory effects were partially reversed by let-7g-5p inhibitors, restoring cell viability and migration by approximately 70%. Mechanistically, LINC02381 functioned as a competing endogenous RNA (ceRNA), directly binding to let-7g-5p and mitigating its suppression of THBS1. Conclusions:LINC02381 promotes OA progression by acting as a ceRNA for let-7g-5p, thereby upregulating THBS1 expression. This signaling axis represents a potential therapeutic target for OS.