To investigate the causes, manifestations, risk factors and management of anesthetic complications of extensive spinal nerve block (ESNB) and total spinal anesthesia (TSA) during percutaneous spinal endoscopic surgery under local anesthesia. We retrospectively reviewed 16,798 patients who underwent percutaneous spinal endoscopic surgery under local anesthesia across three institutions between February 2012 to February 2023. Patient demographics, including gender, age and Body Mass Index (BMI) were collected, along with surgical characteristics such as surgical sites, involved segments, surgical approaches and procedures. Local anesthetic dosage, as well as the onset time, manifestations, management, recovery and prognosis of intraoperative ESNB and TSA were recorded. Statistical analysis including regression analysis was used to identify potential risk factors. 9 patients (0.05

Spine-pelvic parameters and lower limb alignment serve as key clinical indicators in orthopedics. It remains unclear whether these measures are interrelated. This study examines the relationship between spine-pelvic parameters and coronal lower extremity alignment in individuals with low back pain (LBP). We prospectively enrolled LBP patients aged over 50 years from April 1, 2023 to September 30, 2025. Radiographic evaluation included standing full-spine lateral and posteroanterior views, along with lower extremity posteroanterior radiographs. Spine-pelvic parameters assessed were pelvic incidence (PI), lumbar lordosis, pelvic tilt, sacral slope, sagittal vertical axis, and coronal balance distance. Lower extremity parameters included the hip-knee-ankle angle (HKA) and Kellgren-Lawrence grade. Parameters were compared across groups, and correlation analyses were conducted. The study included 264 patients (mean age 64.1±7.3 years; 63.6

Low back pain (LBP) is the leading cause of non-fatal disability globally, significantly affecting quality of life and imposing an immense socioeconomic burden. Intervertebral disc degeneration (IVDD) is a major cause of LBP. Although advances in biomaterials and drug delivery have provided new therapeutic options, their efficacy remains limited by invasive delivery approaches and the spatiotemporal dynamic changes in the microenvironment during treatment. In recent years, smart biophysical cue-based strategies—represented by electrical, magnetic, photo, ultrasonic, and mechanical cues—have offered breakthrough noninvasive or minimally invasive approaches for IVDD intervention. Such cues can act directly or indirectly on disc tissues, modulating oxidative stress signaling pathways, optimizing the inflammatory microenvironment, and influencing cellular behavior and extracellular matrix metabolism, thereby delaying or even reversing the degenerative process. These modalities possess highly controllable and precise regulatory potential for tissue repair and can synergize with intelligent biomaterials, drug delivery systems, and other therapeutic strategies to achieve multi-dimensional and multi-targeted regulation. Current research in this field has largely concentrated on isolated biophysical cues or individual material systems, resulting in fragmented advances and a lack of systematic cross-comparison, which limits their translational relevance for precise clinical intervention. This review goes beyond single-cue perspectives to provide a comprehensive and comparative integration of multiple biophysical cue-based strategies and materials within the IVDD field, systematically elucidating their mechanisms of action and developmental trajectories. Moreover, from an interdisciplinary perspective, this review provides new theoretical foundations and directions for precision therapy in IVDD.

Osteoporotic implant fixation failure arises from a resorption-biased peri-implant niche in which inflammation, oxidative stress, impaired angiogenesis, and defective osteogenesis collectively undermine stable osseointegration. Here, we report an injectable, bone-affinitive, calcium-enriched CAFG hydrogel as an interfacial biomaterial platform for reprogramming the osteoporotic peri-implant microenvironment and reinforcing implant anchorage. Constructed from oxidized fucoidan, gelatin, and CaCO3@ALN nanoparticles, the hydrogel integrates rapid in situ gelation, injectability, self-healing, wet adhesion, and local bone-targeting capability, enabling persistent interfacial retention and multifunctional bioactivity. Beyond structural stabilization, CAFG hydrogel actively remodels the pathological peri-implant niche by alleviating oxidative stress and inflammatory injury, promoting macrophage polarization toward a pro-regenerative phenotype, restoring endothelial angiogenic behavior, suppressing osteoclastogenesis, and enhancing osteogenic differentiation and matrix mineralization. Transcriptomic analysis further reveals that CAFG hydrogel-5% reverses LPS-induced inflammatory and osteoclast-associated programs while restoring extracellular matrix organization and osteogenesis-related signatures. In an ovariectomy-induced osteoporotic rat femoral screw model, local peri-implant delivery of CAFG hydrogel-5% significantly enhances peri-implant bone formation, collagen deposition, and vascularization, reduces inflammatory and osteolytic responses, and markedly improves pull-out strength. Collectively, this study establishes a multifunctional hydrogel-based strategy that couples interfacial stabilization with microenvironmental reprogramming, offering a promising materials framework for improving osseointegration and durable fixation in mechanically compromised bone.

Abstract The locomotor system organoids, which recapitulate bones, cartilage, tendons, muscles, and associated neurovascular-like structures, possess complex architecture and biomechanical properties. Traditional two-dimensional (2D) cell models struggle to effectively mimic their physiological functions. Organoid technology, through three-dimensional (3D) culture and cellular self-organization, offers an innovative paradigm for modeling developmental and pathological processes of the locomotor system. However, accurately constructing locomotor system organoids with highly biomimetic properties still presents the core challenge of reconstructing the extracellular matrix (ECM), the mechanical microenvironment, and dynamic biological cues. Bioactive materials, such as natural hydrogels, decellularized matrices (dECM), and synthetic hydrogels, serve as key supporting materials, not only providing a 3D scaffold for cells but also guiding stem cell differentiation and tissue self-organization by modulating physicochemical properties and biological cues. From the perspective of material-driven microenvironment regulation, this paper systematically reviews the construction strategies, research progress and translational applications of locomotor system organoids, analyzes the key challenges of standardization, vascularization and immune microenvironment integration. Finally, the integrated application of intelligent responsive materials, four-dimensional bioprinting and artificial intelligence is prospected to provide a future direction for the biomimetic optimization and clinical translation of locomotor system organoids.

The increasing prevalence and incidence urge efficient treatment of osteoarthritis (OA). In contrast, a single modality is hard to combat OA's complicated pathogenesis and achieve comprehensive chondroprotective function. Through RNA sequencing, we identified bone marrow mesenchymal stromal cell-derived exosomes (BMSC-Exo) and cartilage progenitor cell-derived exosomes (CPC-Exo) have distinct enrichment of miRNA contents, emphasizing macrophage and chondrocyte modulation, respectively. Thus, inspiring us to develop a bi-exosome combination strategy, which combines anti-inflammatory BMSC-Exo and anti-catabolic CPC-Exo, to alleviate osteoarthritis progression via simultaneous regulation of macrophage polarization and chondrocyte phenotype. Once delivered into the rat knee joint cavity by hyaluronic acid methacryloyl microspheres, the bi-exosome combination remarkably postponed OA progression via combating the joint inflammatory and catabolic environment, in which the dominant interventive pathways (i.e., miR-708-5p/NRP-1, miR-431/BRCA-1/PLK-1, and miR-7a-5p/NOTCH-3) were further revealed. This work presents the tailoring of exosome compositions to modulate multitargeting, thereby creating a potential for OA treatment.

Postoperative radiculitis secondary to excessive L5 nerve root retraction is a debilitating complication of posterior lumbar interbody fusion (PLIF). Despite its clinical prevalence, surgeons lack a standardized, visual safety threshold, often relying on intraoperative experience and tactile feedback. This study utilized maximum physical retraction distance as a practical but incomplete proxy for mechanical nerve stress to explore a potential risk threshold and evaluate its mid-term clinical impact. In this retrospective cohort study, we analyzed 80 patients who underwent PLIF. All procedures were performed using a standardized technique to ensure consistency. The maximum intraoperative transverse retraction distance of the L5 nerve root was recorded. The primary endpoint was the development of postoperative radiculitis. The optimal diagnostic cutoff was determined via receiver operating characteristic (ROC) analysis. A Cochran-Armitage test assessed the dose-response relationship, and 6-month visual analog scale (VAS), Oswestry Disability Index (ODI), and reintervention rates were evaluated. Postoperative radiculitis developed in 18 of 80 patients (22.5

Study Design Retrospective study. Purpose To evaluate the influence of lipid parameters on vertebral bone quality (VBQ) scores in patients undergoing lumbar fusion surgery. Overview of Literature The MRI-derived VBQ score is a validated tool for assessing osteoporosis in patients undergoing lumbar fusion surgery. However, the effect of lipid parameters on its diagnostic performance remains unclear. Methods Consecutive patients who underwent lumbar fusion surgery over a 3-year period were retrospectively reviewed. Inclusion required the availability of lumbar T-scores, quantitative computed tomography, magnetic resonance imaging (MRI), and laboratory data obtained within a 1-month interval. Patients were stratified according to lipid levels and clinical characteristics. Correlation analysis and receiver operating characteristic (ROC) curve analysis evaluated the impact of lipid parameters on VBQ 1.5T, VBQ 3.0T, and the calibrated VBQ (C-VBQ) scores, which was developed to improve consistency across different MRI field strengths. Results This study included 294 patients (mean age, 67.1±6.5 years; 57.8% female; 56.8% with hyperlipidemia). Among the lipid parameters evaluated, only high-density lipoprotein cholesterol (HDLC) demonstrated a modest association with VBQ scores. Correlation analysis demonstrated significant positive correlations between HDLC and both VBQ 1.5T (p=0.003) and C-VBQ (p=0.001). After stratification by HDLC levels, C-VBQ differed significantly between normal and abnormal HDLC groups (p=0.046). Significant differences in VBQ 3.0T and C-VBQ across HDLC quintiles persisted even after T-score adjustment (p=0.037 and p=0.003). ROC analysis revealed minimal influence of lipid parameters or hyperlipidemia on VBQ diagnostic performance. Conclusions Among lipid parameters, only HDLC was positively associated with VBQ scores; however, this weak association did not significantly compromise the diagnostic performance of VBQ for osteoporosis.

The acidic tumor microenvironment (TME) promotes immune escape by suppressing T-cell function, creating a major barrier to immunotherapy. Here, acidic pH-mediated impairment of T cell responses via the proton-sensing receptor GPCR68 is identified, whereas mild extracellular alkalinization counteracts this pathway to restore T cell effector function. GPCR68 acts as a negative regulator of T cell–driven anti-tumor immunity, as evidenced by the enhanced cytokine production (IFN-γ, TNF-α) and suppressed tumor growth in T cell–specific GPCR68 knockout mice (GPCR68fl/flCD4Cre). Thus, a borate-optimized local tumor therapy (BOLT) strategy is engineered to target GPCR68, based on alkali-metal-ion-modulated borate bioactive glass, which is integrated, spatiotemporally multiple responsive, and locally injectable. BOLT combats tumors dually by potentiating T cell immunity and inducing tumor ferroptosis. It alleviates acid suppression of T cells via GPCR68 inhibition and PI3K/AKT/mTOR signal activation, while promoting ferroptosis through the upregulation of Duox1/ROS and suppresseion of NRF2/SLC7A11/GPX4 axis. Therapeutically, BOLT synergizes with anti-CTLA4 blockade to overcome immunotherapy suppression and markedly enhances tumor immunity. These findings establish GPCR68 as a critical pH-sensing regulator of T-cell function and a therapeutic target for pH-based immunomodulation, and propose BOLT as a translational strategy for “alkaline intervention therapy” to potentiate immunotherapy.

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain. Although the mechanical functions of the nucleus pulposus (NP) critically relies on its viscous dissipation, the role of this property in IVDD remains unclear. Here, we established a correlation between reduced NP viscous dissipation and disease severity in both clinical specimens and a rat model. Using engineered hydrogels that independently mimic the viscous dissipation properties of healthy and degenerated NP, we found that decreased viscous dissipation induces NP cells (NPCs) senescence by suppressing YAP. Further mechanistic investigation revealed that NPCs likely sense changes in extracellular matrix (ECM) viscous dissipation primarily through ITGB1, which subsequently regulate cell adhesion and inhibit YAP activity. Downstream of YAP, reduced viscous dissipation leads to decreased nuclear envelope integrity and aberrant accumulation of cytosolic DNA in NPCs, thereby activating the cGAS-STING pathway and driving NPCs senescence. The senescence of NPCs induced by these events changed the components of ECM, which may further reduce viscous dissipation, potentially creating a vicious cycle. By pharmacological activation of YAP and the implantation of a mechanically biomimetic hydrogel, we alleviated the vicious cycle and suppressed IVDD progression in vivo. These findings provide important insights into the pathogenesis of IVDD and suggest promising therapeutic strategies.

Low back pain affects 70-85 % of adults globally, with intervertebral disc degeneration (IVDD) driving nearly half of cases. Integrating human genetic evidence from a large-scale genome-wide association study in up to 829,699 participants along with immunofluorescence staining of nucleus pulposus in patients with varying degrees of IVDD, we identified PI3K-Akt signaling as a central pathway in lumbar disc herniation. Guided by this genetic blueprint, we engineered a piezoelectric scaffold GelMA-FF (GF) which can transform physiological loading into regenerative bioelectrical signals, and regulate PI3K-Akt pathway. The GF system synergizes gelatin methacryloyl's biomechanical compatibility with diphenylalanine crystals' piezoelectric capacity, directly targeting fixed charge density restoration-the electrophysiological hallmark of IVDD. The results reveal that GF-generated electrical signals could change the pathogenic PI3K-Akt/NF-κB axis, shifting disc metabolism from inflammatory catabolism to anabolic regeneration. This GF system also enhances mitochondrial energetics and extracellular matrix synthesis, achieving structural and functional recovery in preclinical models. This study proposes a novel strategy-a paradigm where genetic risk architectures guide physiology-matched biomaterials to transduce endogenous mechanical microenvironment cues into regeneration signals.

Study Design Retrospective case series. Objective The single-position prone lateral lumbar interbody fusion (P-LLIF), which eliminates the need to change patient decubitus during the procedure, represents a modification of the traditional lateral lumbar interbody fusion (LLIF). This pioneering study aims to investigate the positional shifts of retroperitoneal organs and changes in lumbar lordosis angle across different decubitus, providing novel insights into the biomechanics of LLIF. Methods Eighteen patients scheduled for LLIF were included. CT scans were performed in 3 positions: prone, right lateral, and oblique decubitus. Measurements included the anatomical positions of the psoas major, abdominal aorta, left common iliac artery, and left kidney at intervertebral disc levels, as well as changes in lumbar lordosis angle across the 3 positions. Results In the prone decubitus compared to the lateral decubitus: The thickness of the psoas major increased by 4.07 ± 3.41 mm. The abdominal aorta shifted laterally by 2.29 ± 2.79 mm. The left common iliac artery shifted laterally by 1.98 ± 3.54 mm. The kidney moved anteriorly by 6.97 ± 5.84 mm. The lumbar lordosis angle increased by 7.73 ± 3.76°. In the oblique decubitus compared to the lateral decubitus: The thickness of the psoas major increased by 3.14 ± 3.36 mm. The abdominal aorta shifted laterally by 1.59 ± 2.82 mm. The left common iliac artery shifted laterally by 2.45 ± 4.51 mm. The kidney moved anteriorly by 3.92 ± 4.70 mm. The lumbar lordosis angle increased by 3.04 ± 3.55°. Conclusion P-LLIF induces significant positional changes in retroperitoneal organs and increases lumbar lordosis angle compared to traditional LLIF. These findings offer critical insights for preoperative planning and underscore the importance of optimizing safety protocols in P-LLIF procedures.

Understanding the sagittal alignment of the pelvis and spine is essential for evaluating adolescent idiopathic scoliosis (AIS). Comparative studies of sagittal characteristics between AIS subtypes (especially lumbar scoliosis) and healthy Chinese adolescents remain limited. This study evaluates differences in sagittal spinopelvic alignment between adolescent females with Lenke type 5 and 6 AIS and the healthy counterparts. This study enrolled 156 female patients with AIS (118 Lenke type 5 and 38 Lenke type 6) and 110 age-matched healthy female adolescents. Spinal and pelvic parameters were measured from standing full spine anteroposterior and lateral radiographs, including the main Cobb angle (MCC), minor thoracic curve for type 6, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic incidence to lumbar lordosis (PI-LL) mismatch, and pelvic tilt (PT). ANOVA compared the dependent variables between the two AIS subtypes (Lenke type 5 and 6) and healthy adolescents, and Pearson’s correlation coefficient (r) was used to determine the relationships among the parameters. PI, LL, SS and PI-LL did not significantly differ between AIS patients and controls. PT differed significantly among groups (p = 0.04). TK was significantly lower in Lenke type 6 compared to Lenke type 5 (p < 0.017 ). Subgroup analysis revealed no significant correlations between sagittal parameters and curve severity or direction in Lenke type 5. The difference between the major and minor curves of type 6 showed a statistically significant correlation with thoracic kyphosis (r = 0.372, p = 0.036) and PI-LL (r = -0.342, p = 0.043). There was statistically significant correlation between the MCC of Lenke type 6 and PI-LL (r =-0.38, p = 0.032). PT reduction as a potential early compensatory trend in Lenke 5, though its predictive utility requires longitudinal validation. The stability of PT across different severities highlights its potential as a marker for early intervention, whereas Lenke 6 appeared to rely more on thoracic curvature adjustments. Dynamic changes in PT and TK may serve as early predictors for lumbar scoliosis progression and elucidate compensatory mechanisms of spinal curvature. These findings could provide clinical guidance for early prevention and targeted therapeutic interventions.

Despite advancements, metallic materials for load-bearing medical applications still face ongoing challenges. Titanium (Ti) and tantalum (Ta) are widely used due to their mechanical and biological properties, but both have limitations: Ta is highly bioactive but heavy and expensive, while Ti is lightweight but less bioactive. Metal additive manufacturing (AM) offers a new pathway for the design of porous metallic biomaterials. This study developed a 50 wt% Ti-Ta alloy for orthopedic implants using in situ alloying capability from laser powder bed fusion (LPBF) AM to combine Ti's lightweight with Ta's bioactivity. Extensive evaluations, including fatigue testing, wettability analysis, and in vitro and in vivo biocompatibility assessments, revealed the superior fatigue and biocompatibility performance of LPBF-fabricated Ti-Ta alloys compared to pure Ti. The alloy demonstrated exceptional fatigue resistance, enduring up to 105 cycles at 110 % of yield strength, and achieved a 40 % bone-implant contact rate 12 weeks after implantation in rabbit femurs. For the first time, this study uncovered the critical influence of LPBF process parameters (i.e., laser power and scan speed) on the microstructures, mechanical properties, and biocompatibility of Ti-Ta alloys. These findings validate LPBF's capability to produce bioactive, mechanically robust Ti-Ta scaffolds, underscoring their potential for advanced orthopedic applications.

This study addresses the clinical challenge of nonunion in spinal interbody fusion by developing a novel composite implant: a porous tantalum (PTa) cage loaded with concentrated growth factors (CGF). The CGF-PTa cage synergistically combines the mechanical strength and osteoconductivity of chemically vapor-deposited PTa with the sustained release of angiogenic (VEGF) and osteogenic (TGF-β and IGF-1) factors from CGF. Using a rat extreme lateral interbody fusion (XLIF) model, the research systematically evaluates the efficacy of this composite in promoting bone regeneration and spinal fusion. Results from radiography, micro-CT, biomechanical testing, histological staining, and immunohistochemistry consistently show that CGF-PTa significantly enhances bone ingrowth, fusion rate, and mechanical stability compared to PTa alone. The findings also reveal that CGF facilitates angiogenesis and osteogenesis by modulating the local healing microenvironment and promoting vascular–osteogenic coupling. Importantly, the CGF-PTa system demonstrated excellent biocompatibility and biodegradability in vivo, with no observed systemic toxicity. This work highlights the potential of combining bioactive factors with porous metallic scaffolds to overcome the limitations of inert implants in avascular environments, offering a promising strategy for functional optimization of interbody fusion devices and their future clinical application.

Previous studies have shown that percutaneous kyphoplasty (PKP) performed as a day surgery achieves similar efficacy to inpatient treatment. However, with the increasing adoption of day-case PKP, some patients experience poor postoperative prognosis, such as delayed discharge, new-onset vertebral fractures, and persistent low back pain. Despite this, research on the risk factors associated with poor prognosis following day-case PKP remains limited. This study aims to investigate the risk factors for poor prognosis in patients undergoing day-case PKP. A retrospective analysis was conducted on 424 patients with osteoporotic vertebral compression fractures (OVCF) who underwent day-case PKP in the Spine Surgery Department of Tianjin Hospital between January 2020 and December 2022. Detailed clinical data were collected for each patient, including age, sex, height, weight, history of hypertension, diabetes, prior fractures, smoking history, length of hospital stay, bone cement volume, paraspinal muscle area and fat infiltration, as well as Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) scores. Univariate analysis and multivariate logistic regression analysis were performed to identify risk factors for poor prognosis following day-case PKP. Univariate analysis revealed significant differences between the new vertebral fracture group and the control group in terms of QCT values (X²=8.933, P = 0.003), history of prior fractures (X²=19.882, P < 0.001), and FCSA (t = 2.626, P = 0.009). Significant differences were also found between the persistent low back pain group and the control group regarding smoking history (X²=9.425, P = 0.002) and Fat Infiltration Percentage (FI

Intervertebral disc degeneration is the leading cause of low back pain, imposing significant burdens on patients, societies, and economies. Advancements in regenerative medicine have spotlighted extracellular vesicles as promising nanoparticles for intervertebral disc degeneration treatment. Extracellular vesicles retain the potential of cell therapy and serve as carriers to deliver their cargo to target cells, thereby regulating cell activity. This review summarizes the biogenesis and molecular composition of extracellular vesicles and explores their therapeutic roles in intervertebral disc degeneration treatment through various mechanisms. These mechanisms include mitigating cell loss and senescence, delaying extracellular matrix degeneration, and modulating the inflammatory microenvironment. Additionally, it highlights recent efforts in engineering extracellular vesicles to enhance their targeting and therapeutic efficacy. The integration of extracellular vesicle-based acellular therapy is anticipated to drive significant advancements in disc regenerative medicine. The translational potential of this article: Existing clinical treatment strategies often fail to effectively address the challenges associated with regenerating degenerated intervertebral discs. As a new regenerative medicine strategy, the extracellular vesicle strategy avoids the risks associated with cell transplantation and shows great promise in treating intervertebral disc degeneration by carrying therapeutic cargo. This review comprehensively examines the latest research, underlying mechanisms, and therapeutic potential of extracellular vesicles, offering a promising new strategy for intervertebral disc degeneration treatment.

Abstract Objective The purpose of this study was to evaluate the feasibility and the trajectories of dual sacral-2 alar-iliac (S2AI) screw fixation with three-dimensional digital technology simulation analysis. Methods The pelvic computed tomography scan data of 60 (30 men and 30 women, age: 25–86 years) individuals were selected and reconstructed. The trajectories of dual S2AI screws were plotted using three-dimensional reconstruction software. A cylinder with a radius of 5 mm was selected to simulate screw placement. If screw placement based on the cylinder with 5 mm radius failed, selected a cylinder with a radius of 4.5 mm or 4 mm. Dual S2AI trajectories were simulated, the maximum length and width of the trajectories were ensured, and their parameters were precisely measured. All parameters were measured in the three-dimensional image, including distance parameters, radius and angles. Results The placement of dual S2AI screws on the same side could be achieved in all individuals. No significant differences were found between the male and female regarding the head inclination angle, abduction angle, and total length or thread length of screws in the same position (P > 0.05). LH(the shortest distance from the greater sciatic notch to the cross-section of the screw trajectory)were17.52 ± 3.96 mm and 14.18 ± 2.92 mm in L1,28.19 ± 2.58 mm and 25.54 ± 4.15 mm in L2, 16.09 ± 4.08 mm and 14.71 ± 3.94 mm in R1, 26.90 ± 3.76 mm and 24.59 ± 2.85 mm in R2 in male and female models, respectively. The shortest distance from the greater sciatic notch to the cross-section of the screw trajectory differed significantly between the sexes (P < 0.05). Conclusion Using a radius of 4 mm (minimum diameter of S2AI screw) as a standard, it is feasible to place two S2AI screws on the same side for the Chinese adult. Screw placement can be achieved by trisecting the lateral process of S1-S2, with one screw inserted in the bottom third and the other in the upper third. Furthermore, preoperative three-dimensional digital technology simulation analysis can effectively simulate the dual S2AI screws trajectories on the same side, and they can provide accurate data for clinical applications.

Background:Multiple studies have shown that the transferrin receptor (TFRC) is highly expressed in various tumors, and it has been recognized as a cancer biomarker. However, its role in osteosarcoma(OS) has rarely been studied. The purpose of this study was to explore the role and mechanism of TFRC in the proliferation, invasion, and migration of osteosarcoma cells. Methods:First, we analyzed the expression of TFRC in OS and normal cells with an open database and evaluated the correlation between TFRC expression and overall survival in OS patients. Quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemical staining were used to determine the expression level of TFRC in OS cell lines and tissues. TFRC was knocked down by lentivirus-mediated short hairpin RNA (shRNA) in 143B and U2OS cells. The effects of TFRC knockdown on OS cell proliferation, migration, and invasion, as well as its mechanism related to ribonucleotide reductase M2 (RRM2), were explored through a series of experiments. Nude mice were inoculated with xenogeneic OS cells to study the influence of TFRC knockdown on tumor growth in vivo. Results:TFRC was highly expressed in osteosarcoma, and its high level of expression was associated with poor overall survival in osteosarcoma patients. After TFRC was knocked down, the proliferation, migration and invasion ability of OS cells were significantly reduced, and TFRC knockdown effectively inhibited the growth of OS cells in xenograft experiments with nude mice. The knockdown of TFRC led to a decrease in the total intracellular iron content and a significant decrease in the protein expression of RRM2. The decrease in the proliferation, migration and invasion of osteosarcoma cells caused by TFRC knockdown was reversed by the addition of FAC or plasmids to overexpress RRM2. Conclusion:OS cells regulate proliferation, migration, and invasion by overexpressing TFRC, which increases the transport of iron into cells and increases the expression and activity of RRM2.

Focal articular cartilage defects often progress to osteoarthritis, imposing a substantial global health burden. Current neglect of cartilage developmental regulation and cartilage microenvironment compromises therapeutic efficacy. We developed an innovation CE-SKP/CPH/P2G3 scaffold which effectively repairs focal cartilage defects and emulates native cartilage ontogeny: the superficial CE-SKP hydrogel layer recruits SMSCs and promotes chondrogenesis; the middle CPH hydrogel layer induces chondrocyte hypertrophic calcification, forming cartilage calcified layer; and the basal P2G3 nanofiber membrane isolates subchondral cells, enforcing a top-down developmental sequence and preserving a localized hypoxic niche. In vitro characterization confirms that the porosity, swelling ratio, biodegradation rate, and biocompatibility are optimal for sequential SMSC recruitment, cartilage differentiation, hypertrophic mineralization, and cells isolation. In vivo, the biomimetic tri-layer scaffold promotes regeneration of both cartilage and calcified cartilage by recapitulating the native ontogenetic progression from cartilage to calcified cartilage within the in vivo microenvironment, successfully restoring the normal physiological structure of articular cartilage by 24 weeks post-implantation. ScRNA-seq revealed SMSCs and a novel chondrocyte subpopulation CHON_5 as key repair populations, SMSCs mediated early repair via hypoxia response and migration, while CHON_5 promoted ECM remodeling, synergistically enhancing regeneration in late repair stage. Furthermore, we identified FGF signaling (FGF2-FGFR1/2 and FGF18-FGFR1/2 pairs) was crucial for MSC-CHON_5 communication during sequential cartilage regeneration. Overall, by recapitulating native developmental dynamics and microenvironmental cues, this scaffold offers a novel and effective strategy for functional cartilage regeneration and osteoarthritis treatment.