Nuclear pore complexes (NPCs) and their constituent nucleoporins (Nups) play essential roles in chromatin organization and gene regulation, yet their functions in osteoclastogenesis remain unclear. Here, we showed that most Nups were down-regulated during osteoclast differentiation. Overexpression of Y-complex Nup133 impaired osteoclast formation by enhancing NPC assembly. We identified that chromatin underwent dynamic reorganization during osteoclast maturation and multinucleation, marked by heterochromatin shifts from the nuclear periphery to the nuclear center, regulated by NPCs. ATAC-seq data revealed increased accessibility of Dnmt3a and Ezh2, while most genes became less accessible. Inhibition of Dnmt3a and Ezh2 disrupted osteoclast differentiation and protected against bone loss in osteoporotic mice. Comprehensive analyses using H3K27me3 and H3K27ac ChIP-seq, together with DNA methylation-seq, showed descriptive changes in epigenetic features during osteoclastogenesis. These findings highlight the significant roles of NPCs and epigenetic regulators in osteoclastogenesis, offering new insights into potential therapeutic targets for bone diseases.

Rationale: Bone fractures, particularly in aging populations, present significant clinical challenges due to prolonged healing times and increased risk of complications. A deeper understanding of the molecular mechanisms regulating bone metabolism and repair is essential for developing novel therapeutic strategies. Methods: Through performing immunohistochemical staining and observation on the hind limbs of mice, we evaluated the differences in the spatial distribution of osteoclasts and sialic acid-enriched regions, and further investigated the correlation between osteoclast activation and sialic acid levels in the bone microenvironment. Additionally, single-cell sequencing was conducted to infer the main cell subsets involved in the modification of sialic acid levels in the periosteum. Meanwhile, in vitro and in vivo models were employed to specifically interfere with neuraminidase 1 (NEU1) activity, so as to verify the effectiveness of targeted regulation of NEU1 in modulating local osteoclast activation, maintaining cortical bone homeostasis, and regulating fracture healing rate. Results: Through single-cell RNA sequencing of human periosteum, we discovered that NEU1 desialylates α2,3-linked sialic acid residues on osteoclasts, disrupting cell-cell recognition and maintaining osteoclasts in a mononuclear state. This mechanism contributes to the low metabolic activity and structural integrity of cortical bone while enhancing bone anabolic effects. Importantly, targeted inhibition of NEU1 in mouse models accelerated fracture healing, reducing healing time by up to 30% compared to controls and significantly improving bone quality and mechanical strength. Conclusions: Here, we identify a critical role for periosteal fibroblast-derived NEU1 in modulating osteoclast activity and bone homeostasis. These findings suggest that NEU1 is a promising therapeutic target for enhancing bone regeneration and treating metabolic bone diseases. Our study lays the groundwork for the development of NEU1-targeted therapies that could transform clinical practice by promoting faster and more effective bone healing.

Neutrophils are central mediators of innate defense in bone marrow, where infection rapidly reshapes local hematopoietic and immune niches. Here, we identify a subset of Mrgpra2+ neutrophils that supports antimicrobial immunity through neutrophil extracellular trap (NET) formation during bone marrow infection. Using a murine Staphylococcus aureus marrow infection model, we show that Mrgpra2 is enriched in neutrophil precursors and supports their survival and effector activation under infectious stress. Single-cell and bulk transcriptomics show that Mrgpra2+ neutrophils exhibit a transcriptional program enriched for NET formation and inflammatory signaling. Mechanistically, Mrgpra2 and TNFR signals converge on a PLC-Ca2+-PKC-NADPH oxidase axis to drive reactive oxygen species (ROS)-dependent NET release while preserving neutrophil viability. In vivo, Mrgpra2 deficiency impairs bacterial clearance, exacerbates tissue injury, and reduces the therapeutic benefit of β-defensin. These findings define a marrow neutrophil pathway that couples infection-derived signals with controlled NET deployment to preserve bone marrow immune homeostasis.

Estrogen deficiency after menopause accelerates bone loss by stimulating osteoclast formation and activity, but the molecular pathways that link estrogen signaling to osteoclast regulation remain incompletely defined. Here, we identify the sialyltransferase ST3GAL-I as a key mediator of RANKL-induced osteoclastogenesis. RANKL activates c-FOS to drive ST3GAL1 transcription, whereas estrogen-bound ERα competes with TRAF6 and suppresses this c-FOS-dependent induction. In a clinical cohort of pre-menopausal and post-menopausal women with or without osteoporosis, serum total and α-2,3-linked sialic acid levels increased with age and were highest in post-menopausal osteoporotic patients. Single-cell RNA sequencing of human bone revealed that osteoclasts form a prominent cluster only after menopause, where FOS, CTSK, and ST3GAL1 are strongly co-expressed, and the estrogen-responsive gene PGR is down-regulated. Additionally, in vivo experiments showed that sialidase treatment in estrogen-deficient models effectively reduced osteoclast-mediated bone loss, mimicking the effects of estradiol. These findings define a direct molecular link between loss of estrogen and activation of a FOS-ST3GAL1 sialylation pathway in osteoclasts, providing mechanistic insight into the enhanced bone resorption characteristic of post-menopausal osteoporosis.

BACKGROUND:Skeletal tuberculosis (TB) remains a persistent clinical and research challenge due to its chronic course, osteolytic destruction, and the limitations of existing animal models, which often require high-level biosafety containment or fail to replicate human skeletal pathology. METHODS:This study developed a biosafe, accessible, and versatile murine model of skeletal TB using Mycobacterium smegmatis, a fast-growing, nonpathogenic mycobacterial species with high genomic homology to Mycobacterium tuberculosis. Three infection routes-subperiosteal calvarial injection, intratibial injection, and intracardiac inoculation-were systematically evaluated for their ability to induce localized versus disseminated bone infection under standard biosafety level (BSL)-1 conditions. RESULTS:Subperiosteal calvarial and intratibial injection of M. smegmatis induced localized bone lesions characterized by osteolysis, sequestrum formation, granulomatous inflammation, and increased osteoclast activity. Intratibial infection additionally triggered compartment-specific immune responses, including neutrophil and macrophage expansion, transient B-cell depletion, and activation of interferon-γ+ (IFN-γ+) T cells, reflecting active immune remodeling at the infection site. Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation. Compared to intratibial infection, intracardiac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis. CONCLUSIONS:This M. smegmatis-based murine model provides a straightforward, reliable, and immunopathologically relevant platform for exploring host-pathogen dynamics, immune-driven bone destruction, and early-stage therapeutic testing in skeletal TB, all within standard BSL-1 laboratories. This model fills a critical gap by enabling BSL-1 research into skeletal TB mechanisms and drug development.

Bone is among the most apoptotically active tissues in the body. During remodeling, repair, and disease, dying osteoclasts, osteoblast-lineage cells, osteocytes, mesenchymal stem/stromal cells, and injury-associated cells release apoptotic bodies (ABs) that retain parent-cell-derived cargo and surface ligands. These vesicles are increasingly viewed not only as debris for efferocytic clearance but also as source-specific signalling units that shape skeletal cell fate, immune activity, mineralization, and repair. This review integrates current evidence for ABs across skeletal homeostasis and disease. We first define ABs within the broader extracellular vesicle landscape, emphasizing vesicle heterogeneity, isolation and characterization challenges, and terminology boundaries. We then examine AB sources and recipient interfaces, including osteoclasts, osteoblast-lineage cells, osteocytes, mesenchymal stem/stromal cells, platelet-derived ABs in injury repair, macrophages, osteoclast phagocytes, chondrocytes, and bone lining cells. We further discuss how dysregulated AB signalling contributes to osteoporosis, osteoarthritis, and bone metastasis, as well as alveolar bone destruction, aging-related bone loss, osteochondral mineralization, and bone injury repair. We highlight therapeutic implications, including AB-based or AB-inspired strategies, the cathepsin K (CTSK)-responsive self-assembling peptide nanoparticle OsteoSAVE for in vivo generation of osteoclast-derived ABs, and the hypothesis that antiresorptive therapies may reshape osteoclast-derived AB (OC-AB) production. We also identify unresolved translational questions, including AB lifespan, circulation, source attribution, and direct human validation.

Breast cancer bone metastasis is characterized by aggressive osteolysis, high recurrence, and frequent secondary dissemination, driven by pathological coupling between tumor cells and osteoclasts. Effective local strategies that simultaneously suppress metastatic progression and promote bone regeneration remain limited, and the molecular vulnerabilities of the bone metastatic niche are still incompletely defined. Here, we report a neuraminidase-functionalized injectable hydrogel (HH‑HP@NA) that depletes sialic acid within the bone metastatic niche to disrupt tumor-osteoclast interactions. Neuraminidase was immobilized on hydroxyapatite nanoparticles and encapsulated within a hyaluronic acid hydrogel, enabling sustained local release and enhanced enzymatic stability under acidic conditions. HH‑HP@NA markedly inhibited osteoclast fusion by reducing surface sialylation, suppressed migration of MDA-MB-231 breast cancer cells. In a murine model of breast cancer bone metastasis with postoperative residual tumors, local administration of HH‑HP@NA achieved up to 84% tumor growth inhibition, significantly prolonged survival, and effectively prevented secondary pulmonary metastasis. Micro-CT and histological analyses further demonstrated substantial attenuation of tumor-induced osteolysis and restoration of bone microarchitecture. These results identify sialylation as a therapeutic vulnerability in the bone metastatic niche and support neuraminidase-functionalized hydrogels as a strategy for treating breast cancer-induced bone defects. STATEMENT OF SIGNIFICANCE: • Breast cancer bone metastasis functions as a metastatic reservoir that promotes systemic dissemination, yet existing bone-targeted therapies fail to block postoperative recurrence and secondary metastasis. • Aberrant sialylation emerges as a key molecular vulnerability that governs tumor-osteoclast coupling, osteolysis, and metastatic competence within the bone niche. •A neuraminidase-functionalized, microenvironment-adaptive injectable hydrogel enables sustained, localized glycan editing in the acidic bone metastatic environment. • Local desialylation simultaneously suppresses osteoclast fusion, impairs breast cancer cell migration, and disrupts the tumor-osteoclast cycle. • In vivo application results in marked inhibition of residual tumor growth, complete blockade of pulmonary dissemination, and restoration of bone microarchitecture. • Localized glycan modulation is established as a new biomaterial-based paradigm for reprogramming metastatic niches and treating tumor-induced bone defects.

INTRODUCTION:The shortage of highly osteogenic grafts significantly impacts clinical bone repair and reconstruction in clinic. Selective cell retention technology increases the number of bone marrow (BM)-derived osteogenic cells on scaffold materials. A suitable pore size is key for improving the efficiency of BM cell enrichment of scaffold materials. Many materials with a controllable pore size have been developed, but due to ethics policies, only a few have been approved for clinical use. OBJECTIVES:In this study, cortical bone shavings with a small pore size were mixed in different ratios with decalcified bone matrix, which has a relatively larger pore size, to form a new BM enrichment scaffold material with an adjustable pore size (MIX materials). METHODS:We evaluated the in vitro and in vivo enrichment efficiency and osteogenic ability of materials with different pore sizes. RESULTS:MIX material (1:1) had suitable pore size that was beneficial for the effective enrichment of BM-derived cells and cytokines and promoted the proliferation and osteogenic differentiation of mesenchymal stem cells in vitro. A subcutaneous heterotopic transplantation experiment in a nude mouse model confirmed that MIX material enhanced osteoinductive potential and angiogenesis in vivo. Similarly, a large animal model using goats with a critical bone defect (2.5 cm) showed that the osteogenic ability of enriched MIX was superior to that of nonenriched MIX after 3 months. A subsequent self-controlled prospective clinical study demonstrated that the osteogenic ability of enriched MIX material was close to that of an autograft (the clinical gold standard) in lumbar intervertebral fusion surgery. CONCLUSION:MIX scaffold material is an effective choice for the clinical treatment of bone repair and bone reconstruction.

Objective: To investigate the role of osteoclast-derived apoptotic bodies (OC-ABs) in osteoarthritis (OA), specifically their impact on subchondral bone remodeling and disease progression, and to explore potential therapeutic strategies targeting OC-AB-induced pathways. Methods: We utilized a mouse model of anterior cruciate ligament transection (ACLT) to simulate post-traumatic osteoarthritis (PTOA). Levels of OC-ABs were assessed in subchondral bone and correlated with OA severity. Additionally, apoptotic body-deficient MRL/lpr mice were analyzed to evaluate the direct contribution of OC-ABs to OA progression and subchondral bone remodeling. The involvement of OC-ABs in osteogenesis was further examined using mesenchymal stem cells (MSCs), with a focus on the RANKL reverse signaling pathway. The therapeutic potential of rapamycin to counteract OC-AB effects was tested. Results: Increased OC-AB accumulation in subchondral bone was positively correlated with OA severity in ACLT-induced mice. Apoptotic body-deficient MRL/lpr mice demonstrated slower OA progression and maintained more stable subchondral bone architecture, indicating a pathogenic role of OC-ABs in OA. OC-ABs significantly stimulated osteogenesis in MSCs via the RANKL reverse signaling pathway. Treatment with rapamycin effectively reversed OC-AB-induced subchondral bone formation, mitigated OA progression, and inhibited the RANKL reverse signaling pathway. Conclusion: OC-ABs play a critical role in exacerbating OA by promoting subchondral bone remodeling via the RANKL reverse signaling pathway. Rapamycin presents as a promising therapeutic agent capable of mitigating OC-AB-driven pathology, highlighting new avenues for targeted OA treatment.

OBJECTIVE:To evaluate the comparative diagnostic efficacy of metagenomic next-generation sequencing (mNGS) versus conventional microbiological culture in spinal infections. METHODS:A retrospective analysis was conducted in a cohort of 80 patients with suspected spinal infections who underwent concurrent testing via metagenomic next-generation sequencing (mNGS), microbial culture, and histopathological examination. Diagnostic performance of mNGS and microbial culture was compared using a composite clinical reference standard (definitive diagnosis integrating histopathology, clinical history, and laboratory findings) as the diagnostic gold standard. RESULTS:Pathogens were detected in 64 cases (80 %) by mNGS, compared to 34 cases (42.5 %) via conventional microbial culture, demonstrating a statistically significant difference in detection rates (P < 0.001). Using clinical diagnosis (histopathology combined with medical history and laboratory findings) as the gold standard, mNGS exhibited superior sensitivity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) in tissue specimens. Conversely, microbial culture showed higher specificity. In pus specimens, mNGS maintained advantages in sensitivity, accuracy, and PPV, while culture demonstrated higher specificity and NPV. CONCLUSION:Compared to conventional microbial culture, mNGS demonstrates superior diagnostic performance in spinal infections, with significantly higher pathogen detection rates and enhanced sensitivity, accuracy PPV and NPV. mNGS exhibits significant advantages over culture in identifying both common pathogens and fastidious organisms, while also demonstrating robust fungal detection capabilities. Additionally, in tissue specimens, mNGS demonstrates relatively pronounced advantages compared to conventional microbial culture. For purulent specimen testing, comprehensive sensitivity and specificity in diagnosis can be achieved through a combined strategy of mNGS and microbial culture.

Intervertebral Disc Degeneration (IDD) is a multifactorial result contributing to Low Back Pain (LBP) while Cartilage Intermediate Layer Protein-1 (CILP-1) is gradually up-regulated along with IDD. Whether CILP-1 acts in a direct role promoting IDD via regulating matrix metabolism remains to be elucidated. Herein, we firstly detected the expression level of matrix-related phenotypes in nucleus pulposus (NP) cells treated with CILP-1, including ADAMTS, MMPs, IL-6, Collagens, Aggrecan (ACAN) and SOX9. Meanwhile, the phosphorylation levels of MAPKs and NF-κB were detected to explore the involved signalling pathways, which were further validated by inhibition experiments. Furthermore, molecular docking analysis was employed to evaluate the possibility of CD47 acting as the direct receptor mediating CILP's regulation above, which was further validated by immunoprecipitation and inhibition experiment. Our findings have made a comprehensive investigation into the regulatory effect of CILP-1 on the matrix metabolism of NP cells and explored the underlying mechanism.

Bone healing is integral to orthopedic research, focusing on the restoration of bone function through a complex interplay of inflammatory responses, soft callus formation, hard callus development, and the final remodeling phase. While the natural progression of bone healing is a finely tuned process, it can be disrupted by inflammatory dysregulation, ranging from chronic inflammation to acute inflammatory anomalies, and by the depletion of essential repair substances under both chronic and acute conditions. Current strategies to enhance bone healing employ a multifaceted approach, including biochemical modulation of the local microenvironment through essential nutrient supplementation (e.g., calcium and vitamin D), biomechanical optimization via improved internal fixation stability, and advanced regenerative techniques incorporating bioactive factors, stem cell therapies, and functional biomaterials. Despite these efforts, challenges persist in the precise characterization of the local microenvironment and the precise control of in vivo bioactive molecule delivery. This review comprehensively summarizes the current research progress in bone healing, providing significant reference for understanding the mechanisms of bone healing and for guiding further research. It is expected to lay the theoretical foundation for the development of more effective therapeutic strategies for bone healing.

Vitamin D (VD) has been extensively associated with the resistance against tuberculosis (TB); however, the mechanism underlying the reduction in TB susceptibility by VD remains uncertain. In our prior investigation, we discovered the relationship between VD and mycobacterium tuberculosis M.tb-induced aberrant osteoclastogenesis. Here we report that VD diminishes apoptosis in M.tb-infected THP-1 cells through tumor necrosis factor (TNF) signaling pathway. This novel perspective contributes to the elucidation of the intricate relationship between VD and tuberculosis. In this study, THP-1 cells were infected with the Mycobacterium tuberculosis H37Rv strain (M.tb) for 4h at a MOI of 1 and then treated with 1,25-dihydroxy vitamin D (1,25(OH)2D3) (10-6, 10-8, 10-10M) for 1d respectively. RNA sequencing (RNA-seq) was performed, and differential expression analysis was conducted by the R package edgeR. Immunofluorescence (IF) and immunohistochemistry (IHC) techniques were employed for VDR, TNFR1 and TUNEL in TB patients and serum levels of TNF-α and IL6 were measured simultaneously. Furthermore, the utilization of western blot and qRT-PCR techniques was employed to investigate the impact of VD on pivotal molecules involved in the TNF signaling pathway. In addition, Bacillus Calmette-Guérin (BCG, ATCC 35734, derived from M.bovis) and VD were administrated by tail vein and articular cavity injection in vivo. Our findings revealed a robust responsiveness of the TNF signaling pathway to M.tb-induced inflammation, resulting in elevated expression of TNF-α, IL-6, and severe apoptosis. VD exhibited significant inhibitory effect on M.tb-induced inflammation and apoptosis both in vitro and in vivo. This study offers novel insights for vitamin D in the study of tuberculous bone destruction.

BackgroundPeriprosthetic joint infection (PJI) is a significant and challenging complication following total knee arthroplasty (TKA). This study aimed to evaluate the efficacy and safety of treating chronic knee PJI with and without antibiotic-loaded calcium sulfate during two-stage revision surgery.MethodsThis retrospective study analyzed 94 patients with TKA infections who underwent two-stage revision between May 2017 and January 2022 at the First Affiliated Hospital of Zhengzhou University. Key outcomes assessed included infection recurrence rates, postoperative range of motion (ROM), Knee Society Score (KSS), Hospital for Special Surgery (HSS) scores, hematological parameters, and complication rates during the follow-up period.ResultsThe demographic characteristics of the two groups showed no significant differences. The infection control rate was significantly higher in the calcium sulfate group (95.7%) compared to the matched control group (80.9%) (P < 0.05). Both groups demonstrated statistically significant improvements in ROM, HSS, and KSS scores compared to preoperative values (P < 0.05). However, intergroup differences in these outcomes were not statistically significant (P > 0.05). Additionally, there was no significant difference in postoperative complication rates between the two groups.ConclusionThe use of antibiotic-loaded calcium sulfate in two-stage revision surgery for chronic knee PJI ensures sustained local antibiotic release at high concentrations, leading to rapid reduction in inflammatory markers, effective infection control, and a low complication rate. This approach is a safe and effective treatment for chronic knee PJI.

BACKGROUND:Spinal tuberculosis (TB) presents substantial therapeutic challenges as it can lead to severe structural and neurological complications. However, evidence-based therapeutic decision-making is hindered by the limitations of existing classification systems, which lack anatomical specificity, quantifiable parameters, and reliability. METHODS:The classification system proposed herein categorizes spinal TB into four types based on clinical manifestations and radiologic features: type I (mild): single-segment involvement, with <50% vertebral collapse and preserved stability; type II (moderate): paravertebral abscesses extending beyond the height of two vertebrae; type III (severe): single vertebral collapse ≥50%, kyphosis of 30°-60°, and spinal instability; and type IV (extremely severe): kyphosis >60° with sagittal imbalance. Cohen's kappa was used to assess the interrater and intrarater reliability. RESULTS:The proposed classification system demonstrated robust clinical applicability in a cohort of 2520 patients with spinal TB (type I, 160; type II, 242; type III, 1992; and type IV, 126), with excellent interrater reliability [intraclass correlation coefficient (ICC) = 0.925 initial, 0.948 on reassessment] and intrarater consistency (ICC = 0.943). Type III spinal TB was the most common in this classification system, comprising 79.05% of cases. Patients with type III spinal TB exhibited moderate kyphotic deformity (mean Cobb angle: 41.5° ± 10.8°), and 38.4% of these patients had neurological deficits. Patients with type IV spinal TB demonstrated a severe sagittal imbalance (mean Cobb angle: 94.3° ± 23.8°), and 51.6% of these patients had neurological deficits. Multidrug antitubercular therapy achieved a 94.6% success rate in patients with type I spinal TB. For patients with type II spinal TB, computed tomography-guided abscess drainage (mean Hounsfield Units threshold: 22.3) or surgical debridement was selected based on abscess density, yielding a 93.3% clinical cure rate. Management of type III spinal TB involved anterior/posterior debridement with spinal reconstruction tailored to lesion topography, neurological deficit severity, and surgeon's expertise, achieving disease resolution or fusion in 95.5% of patients. Patients with type IV spinal TB underwent corrective osteotomy via posterior-only or combined anteroposterior approach depending on deformity rigidity, achieving a mean kyphosis correction rate of 72.0%. CONCLUSION:The proposed classification system demonstrated high reproducibility and reliability for spinal TB. The classification algorithms and corresponding treatment protocols are based on distinct clinical manifestations and radiographic characteristics. Moreover, this system shows good potential to facilitate standardized therapeutic management of spinal TB.

Study Design: A retrospective study. Purpose: To evaluate the clinical efficacy of uniportal endoscopic decompression and debridement (UEDD) in treating infectious diseases of the spine (IDS) with neurological deficits. Overview of Literature: IDS patients with neurological deficits often require urgent surgical decompression. However, the efficacy of UEDD in this complex patient population is not well-characterized. Methods: This retrospective study analyzed 32 consecutive IDS patients who underwent UEDD surgery. Clinical features, laboratory data (erythrocyte sedimentation rate and C-reactive protein), and treatment outcomes were analyzed. Results: Definite microorganisms were identified in 27 patients (84.3%), with 24 (88.9%) meeting cure criteria. The cure rate was significantly higher in the detected pathogen group compared to the undetected pathogen group (88.9% vs. 80%; chi(2)=19.36, p<0.0001). Metagenomic next generation sequencing (mNGS) provided faster diagnosis (41.72 +/- 6.81 hours) compared to tissue culture (95.74 +/- 35.47 hours, p<0.05). The predominant causative pathogen was Mycobacterium tuberculosis, followed by Staphylococcus aureus. Significant improvements were observed in Visual Analog Scale pain scores, from a mean of 7.9 preoperatively to 1.06 at 1 year postoperatively. The Oswestry Disability Index revealed a similar trend, showing significant improvement (p<0.05). Conclusions: UEDD is a viable alternative to traditional open surgery for managing IDS in high-risk patients. UEDD offers a dual therapeutic-diagnostic advantage during the initial admission phase, enabling simultaneous debridement, neurological decompression, and targeted biopsy in a single intervention. Compared with traditional tissue culture, mNGS enables rapid microbiological diagnosis and extensive pathogen coverage.

Osteoporotic bone defects are challenging to repair due to imbalances in bone resorption and formation, coupled with insufficient vascularization. To address these issues, it develops a trifunctional hydrogel (SF-ZIF@NA) designed to selectively inhibit osteoclast activity and enhance vascularized bone regeneration. By enzymatically removing sialic acid, SF-ZIF@NA prevents precursor osteoclasts (pOCs) from fusing into bone-resorbing mature osteoclasts (mOCs), thereby preserving pOCs and their anabolic functions. Additionally, the hydrogel releases Zinc ion (Zn2⁺) in response to acidic conditions, promoting osteogenesis and angiogenesis. In vitro results confirmed that SF-ZIF@NA impedes osteoclast fusion, enhances platelet-derived growth factor-BB (PDGF-BB secretion from pOCs, and activates the FAK (focal adhesion kinase) signaling pathway to stimulate vascularized bone formation. In osteoporotic bone defect models, SF-ZIF@NA accelerated bone repair with increased bone density and vascularization. These findings demonstrate that SF-ZIF@NA offers a targeted and multifunctional strategy for osteoporotic bone regeneration by concurrently modulating osteoclast activity and promoting angiogenesis.

Purpose:This systematic review and meta-analysis evaluates platelet-rich plasma (PRP) efficacy in anterior cruciate ligament reconstruction (ACLR) through 15-year Randomized controlled trials (RCTs) data, focusing on postoperative recovery, rehabilitation acceleration, and functional outcomes optimization. Methods:We conducted an extensive systematic search in PubMed, Embase, and Web of Science to find relevant studies on using PRP in ACLR. Randomized controlled trials analyzing the comparative effectiveness of PRP compared to control interventions in individuals undergoing ACLR were systematically identified. The focus was on studies that provided reliable outcome measures, encompassing validated clinical assessments and objective imaging results. Outcome indicators included the Visual Analog Scale (VAS) for pain perception, the International Knee Documentation Committee (IKDC) score, Lysholm score, Tegner activity scale, KT-1000 side-to-side difference, graft characteristics, and associated complications. Additionally, subgroup analyses were categorized based on evaluation timelines, distinguishing between preoperative and postoperative assessments. Results:This meta-analysis of 24 studies demonstrated time-dependent effects of PRP supplementation following ACLR. The PRP group exhibited significant improvement in IKDC scores at 12 months post-operatively (mean difference: 2.09, P = 0.01, I2 = 23%), while Lysholm scores showed significant enhancement at 6 months (mean difference: 3.33, P = 0.03, I2 = 58%). Pain reduction, assessed by VAS scores, was significantly greater in the PRP group at 3 months (mean difference: -1.33, P < 0.01, I2 = 38%) with borderline significance at 6 months (mean difference: -0.78, P = 0.05). Notably, PRP intervention significantly reduced anterior tibial translation compared to controls (mean difference: -1.34 mm, 95% CI: -1.56 to -1.13, P < 0.01, I2 = 73%), indicating improved knee stability. Pre-operative KT-1000 measurements suggested a trend toward reduced knee laxity in the PRP group (mean difference: -0.70 mm, 95% CI: -1.45 to 0.05, P = 0.07), though this effect did not persist post-operatively. No significant between-group differences were observed in Tegner activity scores, Signal-to-Noise Quotient, or Pivot Shift Test results at any follow-up interval. Conclusion:This meta-analysis indicates that PRP application during and shortly after ACLR offers limited clinical benefits. Although there is notable short-term pain relief, long-term efficacy remains unclear, with improvements not meeting minimal clinically important differences (MCID) and no significant changes in knee stability or graft maturation. Further research is needed to establish optimal PRP protocols and standardization for ACLR.

Typical oblique lumbar interbody fusion (OLIF) generally employed either the single lateral screw (SLS) or dual pedicle screws (DPS) for instrumentation, each with their own limitations. The study aimed to investigate the biomechanical properties of two additional fixation strategies including single reverse pedicle screw (SRS) and dual overlapped screws (DOS) compared with SLS and DPS. A finite element (FE) analysis study. A L2-5 finite element model was established and validated with L4/5 as the experimental segment. Four fixations including SLS, SRS, DPS and DOS were established on the segment respectively. The L5’s inferior surface was set immobilized. Follower-loaded bending moments were imposed on the superior surface of L2 to record the segment’s range of motion (ROM) and maximum stress (MS) on the screws, cage and cortical bone under F-E (flexion and extension), bending (left and right) and rotation (left and right). The model was validated feasible through comparison with previous studies. Regarding the immediate stability: (i) the ROM was significantly lower in DPS and DOS compared to SLS and SRS during F-E and rotations; (ii) compared to DPS, DOS illustrated mildly increased ROM during F-E motions, and left rotation; (iii) compared to SLS, SRS showed an increase of ROM during flexion but a reduction in extension, without obvious distinctions during other motions. Regarding the mechanical response: (i) DPS and DOS illustrated lower MS on the screws, cortical bone and cage than SLS and SRS during most motions; (ii) Compared to DPS, DOS exhibited increased MS during most motions on the screws, cortical bone and cage; (iii) Compared to SLS, SRS demonstrated an increase of MS on the screws during flexion but an reduction during extension, along with decreased MS on cortical bone and cage during most motions. Dual-screw systems (DPS and DOS) demonstrated enhanced immediate stability for the segment and mitigated mechanical loading for the instrument compared to single-screw systems (SLS and SRS); For the former, DOS exhibited comparable immediate stability to typical DPS, indicating the potential as a viable alternative; For the later, SRS manifested similar stability to traditional SLS, with less stress loading on the cage and cortical bone, indicating less risk of instrument failure in the long term. The study provides biomechanical references to achieve differentiated and individualized instrumentation for patients undergoing OLIF surgery.