This study aimed to identify latent classes of intrinsic capacity (IC) among older adults undergoing total knee arthroplasty (TKA) and to examine the association between IC patterns and short-term postoperative functional outcomes assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Following the Integrated Care for Older People framework, IC was assessed across five domains—cognition, psychology, vitality, locomotion, and sensory function—using validated instruments. WOMAC scores were evaluated preoperatively and at 3 months postoperatively. Latent class analysis was performed to identify IC patterns, and multinomial logistic regression was used to examine factors associated with IC pattern classification. Three IC patterns were identified in older adults undergoing TKA: C1 “Low impairment” (59.34%), C2 “Vit + Psy” (10.75%), and C3 “Loc + Sen” (29.91%). Age, manual labour occupations, and use of walking assistive devices were significantly associated with IC pattern classification (all P < 0.05). After adjustment for baseline WOMAC and other covariates, no statistically significant differences were observed among IC pattern groups in WOMAC scores at 3 months postoperatively or ΔWOMAC (P > 0.05). Identification of IC patterns may enhance the understanding of multidimensional functional heterogeneity among older adults undergoing TKA and provide a potential framework for personalised perioperative assessment and future longitudinal research.

Hallux valgus (HV) is a common foot deformity influenced by genetic, pathological, and traumatic factors, yet its relationship with serum metabolites (SMs) remains unclear. This study employed two-sample Mendelian randomization (SMR) to investigate causal associations between 1400 SMs and HV, identifying Cysteine and Glycochenodeoxycholate 3-sulfate as negatively correlated with HV occurrence, with no significant reverse causal effect from HV on their levels. Focusing on Cysteine, 548 target genes were predicted from four databases (DrugBank, SuperPred, Genecards, and SwissTargetPrediction) and 793 HV-related genes were retrieved from Genecards, yielding 47 overlapping genes. KEGG enrichment analysis revealed that these intersecting genes were involved in pathways such as cellular senescence and the AGE-RAGE signaling pathway in diabetic complications. Among them, fibroblast growth factor receptor 2 (FGFR2) showed a positive causal relationship with Cysteine and a negative causal relationship with HV, which was validated in patient samples showing significantly lower serum Cysteine levels and bone tissue FGFR2 expression in the HV group compared to non-HV controls (p < 0.001). Additionally, Isogranulatimide was identified as a marine-derived active compound targeting FGFR2, with molecular docking and dynamic simulations confirming favorable binding activity. These findings suggest that Cysteine may play a protective role in the development and progression of HV, with FGFR2 serving as a key mediating target that could reduce HV risk both indirectly through elevated Cysteine levels and directly through its own regulation, offering valuable reference for targeted diagnosis and therapy in clinical practice.

Tissue regeneration is a central frontier in biomedicine, yet articular cartilage defect repair in osteoarthritis (OA) remains a formidable challenge. Although mesenchymal stem cell (MSC)-based therapies show great potential for cartilage regeneration, their clinical translation is hindered by sequential barriers: low cell retention, oxidative stress-induced apoptosis, and inefficient MSC homing to defect sites and subsequent integration. Herein, we fabricate chondrogenic niche hydrogel microspheres (Chonichspheres) via microfluidics. These HMs are composed of gelatin methacryloyl (GelMA)/aldehyde-hyaluronic acid methacrylate (AHAMA) composite matrices loaded with amino fullerenes (AF) and transforming growth factor-β3 (TGF-β3). Chonichspheres exert four synergistic functions: GelMA acts as a structural scaffold to promote MSC adhesion; AF exert sustained antioxidant effects to regulate redox homeostasis in MSCs and OA chondrocytes; AHAMA enables precise targeted homing and tissue integration; and TGF-β3 induces MSC chondrogenic differentiation. Validated by an HM-adapted custom microphysiological system (MPS) and in vivo experiments, Chonichspheres activate the integrin-PI3K-AKT-mTOR axis, protecting MSCs and facilitating chondrogenic differentiation under OA-mimicking dynamic culture conditions. By synergizing active covalent tissue integration with durable, non-sacrificial antioxidant defense, this programmatic platform provides a robust precision regenerative strategy for OA cartilage repair.

Reconstruction of chondrocyte homeostasis and amelioration of the immune microenvironment remain major challenges in the treatment of osteoarthritis (OA). Although mesenchymal stem cell (MSC)-derived exosomes (EXOs) possess immunomodulatory and pro-chondrogenic capacities, their heterogeneous composition often results in suboptimal specificity and inconsistent therapeutic outcomes. To address this limitation, we pre-stimulated MSCs with OA-associated inflammatory cytokines (TNF-α, IL-6, and IFN-γ) to generate immuno-activated exosomes with enhanced specificity. Through vivo and vitro experiments, we evaluated the capacity of these exosomes to modulate chondrocyte homeostasis and the inflammatory microenvironment, and further investigated whether they exert a cocktail effect in OA treatment. Our results demonstrate that these immuno-activated exosomes differentially restore chondrocyte homeostasis and ameliorate the inflammatory microenvironment. Notably, a mixture of exosomes derived from distinct cytokine-priming conditions produced a superior cocktail effect compared to any single priming condition alone. Collectively, this integrated strategy provides a novel paradigm and a promising therapeutic avenue for exosome-based OA treatment.

PURPOSE:To investigate the influence of labral augmentation on glenohumeral biomechanics for anterior glenohumeral instability patients via finite element analysis (FEA). METHODS:A shoulder finite element model was derived from preoperative computed tomography scans of five patients with anterior shoulder instability and subcritical glenoid bone loss (13.5%-25% of inferior glenoid width). Four models were established based on the affected shoulders, including a model of Bankart lesion combined with subcritical glenoid bone loss, a model of isolated Bankart repair, a model of Bankart repair plus remplissage, and a model of labral augmentation. The contralateral, unaffected shoulders served as normal controls. These five models were tested to assess humeral head displacement and stress on the joint capsule and cartilage. RESULTS:Labral augmentation outperformed Bankart repair with or without remplissage in restoring native joint characteristics. It limited humeral head displacement to control-like levels (8.10 ± 0.58 vs 7.61 ± 0.46 mm, P = .18), normalized capsular stress (2.00 ± 0.20 vs 1.82 ± 0.23 MPa, P = .221), and reduced cartilage stress on the glenoid and humeral head to pre-injury baselines (glenoid: 2.65 ± 0.18 vs 2.75 ± 0.23 MPa, P = .484; humeral head: 29.70 ± 1.92 vs 30.31 ± 1.93 MPa, P = .630). CONCLUSIONS:In this FEA of anterior shoulder instability with subcritical bone loss, labral augmentation decreased humeral head displacement and restored articular cartilage stress to an intact state compared to Bankart repair with or without remplissage. CLINICAL RELEVANCE:This FEA study suggests labral augmentation in the context of subcritical bone loss may be a viable surgical treatment option for patients with shoulder instability.

Background: Accurate femoral localization is a critical factor influencing graft length-change behavior in medial patellofemoral ligament reconstruction (MPFLR). However, the commonly used Schöttle point is derived from static radiographs and does not account for subject-specific patellofemoral kinematics during active knee motion. In this study, we integrated four-dimensional computed tomography (4D-CT) with constrained optimization to establish a motion-informed, patient-specific femoral localization framework. Methods: A total of 1382 4D-CT knee datasets were screened, and 58 knees were selected for detailed kinematic modeling. Subject-specific femoral and patellar point clouds were reconstructed from time-resolved CT data acquired during voluntary knee flexion. Within a predefined 5–15 mm neighborhood of the Schöttle point, a constrained sequential quadratic programming (SQP) approach was applied to identify an individualized femoral point (I-point) that minimized MPFL length variability while enforcing a femoral-surface constraint. Results: Compared with the Schöttle point, the I-point demonstrated a distinct spatial distribution, characterized primarily by a proximal shift along the femoral axis (PERMANOVA pseudo-F = 4.457, p = 0.006). Across 0–90° of knee flexion, the I-point was associated with reduced MPFL length variation and approached a relatively stable length-change profile near mid-flexion. Conclusions: These findings indicate that integrating 4D-CT-derived kinematics with constrained optimization can provide quantitative, imaging-based, motion-informed guidance for patient-specific femoral localization. This imaging-based framework may serve as a preoperative decision-support tool for personalized MPFLR planning.

Total knee arthroplasty (TKA) is a standard procedure for end-stage knee diseases, yet perioperative bleeding and its complications, such as ecchymosis, remain significant challenges. Predicting ecchymosis can guide personalized perioperative blood management, enhancing patient recovery and reducing the socioeconomic burden. In this prospective study (June 2023–March 2024), 416 TKA patients were split into ecchymosis (n = 135) and non-ecchymosis (n = 281) groups. The first seven months’ data (312 patients) were used for training, and the next three months’ (104 patients) for validation. Feature selection used Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest-Recursive Feature Elimination (RF-RFE), and BORUTA to identify key risk factors. The model was tested with advanced machine learning: Random Forest (RF), eXtreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), and Light Gradient Boosting Machine (LGBM). Major risk factors included low prealbumin, reduced coagulation index (CI) and its change (XCI), high fibrinogen degradation products (FDP), and postoperative day 1 total blood loss (TBL). The model showed robust performance with area under the curve values (AUCs) of 0.927 in training and 0.954 in validation set. The model’s superior high performance offers significant guidance for early and accurate prediction, enabling personalized anticoagulation therapy and optimizing perioperative blood management in TKA patients. Trial registration: Chinese Clinical Trial Registry (registration No. ChiCTR2400080173).

Background: Patellar motion trajectory (PMT) is a key kinematic parameter for evaluating patellofemoral joint (PFJ) stability, but traditional static imaging indices are unable to capture the dynamic six-degrees-of-freedom (6-DOF) characteristics of patellar motion throughout the entire knee flexion-extension cycle. Four-dimensional computed tomography (4D-CT) facilitates in vivo dynamic imaging of the PFJ, while the systematic classification of PMT in asymptomatic populations has remained underexplored. Methods: A retrospective cross-sectional study was performed on 64 asymptomatic and functionally normal knees that underwent 4D-CT dynamic scanning from March 2021 to December 2025. Patellar 6-DOF kinematic data during 0° to 90° of knee flexion-extension were extracted through manifold optimization, automatic segmentation, and spatial registration. Following standardization of the motion cycle, unsupervised K-means clustering was employed to classify PMT phenotypes, with nonparametric tests used to analyze intergroup kinematic differences and evaluate clustering quality. Results: Three distinct PMT types were identified based on clustering validity indices, including a silhouette score of 0.381, a Davies-Bouldin index of 0.916, and a Calinski-Harabasz index of 44.06: Type 1 (7.81%, 35.11 ± 6.56 mm), Type 2 (56.25%, 15.67 ± 6.59 mm), and Type 3 (35.94%, 2.82 ± 2.41 mm). Lateral translation (Tx) served as the dominant determinant for PMT typing (p < 0.001), whereas non-lateral DOF parameters exhibited no consistent intergroup differences. Postural DOFs exhibited coupled fluctuations with Tx but had no independent stratification effect. Traditional static imaging parameters demonstrated no consistent correlation with these dynamic subtypes. Conclusions: Functionally asymptomatic knees exhibited three in vivo patellar 6-DOF motion trajectory phenotypes dominated by lateral translation amplitude. This 4D-CT-based typing framework provides a dynamic kinematic baseline for PFJ stability evaluation and lays a foundation for individualized optimization of ligament reconstruction and pathophysiological research of patellofemoral disorders.

Immunomodulatory microspheres represent an advanced class of biomaterials that function as comprehensive platforms integrating passive drug delivery and active immunoregulatory capabilities. This review synthesizes fundamental design principles-where engineered chemical (e.g., ion release, surface functionalization, redox modulation) and physical (e.g., size, morphology, stiffness) properties synergistically create "immune instruction systems" to reprogram pathological microenvironments. Their transformative applications span multisystem diseases. In orthopedics, microspheres recalibrate macrophage polarization (M1/M2) to resolve osteoarthritis inflammation and promote bone regeneration in osteoporosis. In gynecology, they overcome mucosal barriers to target ectopic lesions in endometriosis and enhance immunotherapy for Premature Ovarian Insufficiency. Moreover, in neurology, they penetrate the blood-brain barrier (BBB) to mitigate neuroinflammation in Alzheimer's disease and stroke. Despite its promise, clinical translation faces challenges, including tissue-specific delivery barriers (e.g., joint clearance, cervical mucus, and BBB penetration) and immune-related safety risks (e.g., cytokine release syndrome). Emerging solutions include stimulus-responsive designs, exosome-microsphere hybrids, and personalized formulations based on immune profiling. Future advancements require scalable manufacturing and long-term safety validation to realize the full potential of these platforms in precision immunotherapy.

Osteoarthritis is a leading degenerative disease worldwide that significantly impairs physical function and quality of life. With an ageing population, the epidemiological burden of osteoarthritis is expected to intensify, making systematic analysis and trend prediction essential for refining treatment and prevention strategies. Data from the 2021 Global Burden of Disease database was employed to analyse trends in the incidence, prevalence, and disability-adjusted life years of osteoarthritis from 1990 to 2021. This research spans global, regional, and national perspectives, aiming to guide future health interventions. By 2021, the number of patients affected by osteoarthritis had reached 607 million, with predictions estimating a rise to 765 million by 2060. There is a positive correlation between Social Development Index and osteoarthritis burden, illustrating that higher incidence and prevalence rates are associated with greater economic development. East Asia currently leads with the highest count of osteoarthritis cases, whereas Oceania has the fewest. Osteoarthritis incidence is climbing across all adult age groups, with women consistently exhibiting higher rates than men at every age. High body mass Index stands as the most significant risk factor for the condition. The total number of osteoarthritis cases is expected to keep rising, underscoring the ongoing challenge in managing this pervasive disease. Osteoarthritis persists as a substantial global health challenge, exhibiting a continuous upward trend from 1990 to 2021. This study provides critical insights for public health policy-making and resource allocation, supporting future interventions and disease control efforts.

Normal mitochondrial function in stem cells is essential for effective bone regeneration, with mitochondrial complex IV (cytochrome c oxidase, CcO) playing a crucial role in sustaining electron transport chain activity and ATP synthesis. To address mitochondrial dysfunction associated with bone defects, we developed a dendritic mesoporous silica nanoparticle (DMSN)-based, CcO-mimetic nanozyme, named triphenylphosphonium (TPP)-DMSN-Fe/Cu. The nanozyme incorporated iron and copper single atoms to mimic the catalytic center of CcO and is modified with the mitochondria-targeting agent TPP. In vitro, TPP-DMSN-Fe/Cu nanozymes colocalized with mitochondria and enhanced mitochondrial function, effectively regulating cellular energy metabolism and promoting stem cell osteogenesis. In vivo, TPP-DMSN-Fe/Cu nanozymes resulted in significantly enhanced bone regeneration compared to the control, resulting in a 177% increase in bone volume and a 12% increase in mineral density at critical-sized bone defects in rats after 4 weeks of treatment. Taken together, these findings demonstrate that bioinspired, mitochondria-targeting TPP-DMSN-Fe/Cu nanozymes hold strong promise for accelerating bone regeneration via regulating cellular energy metabolism.

Metabolism-regulating microspheres have evolved from conventional drug carriers into active platforms capable of spatiotemporally reprogramming pathological metabolic networks. Chronic diseases are increasingly understood to be driven by metabolic dysregulation, highlighting the need for therapeutic strategies that enable localized and precise metabolic intervention. This review systematically outlines the core design principles of these microspheres, emphasizing the synergistic integration of engineered chemical properties, such as ionic signaling, metabolite delivery, and pathway modulator release, with tailored physical characteristics, including stiffness, porosity, and size of the microspheres. Together, these features construct “metabolic instruction systems” that correct dysregulated pathways at the tissue level. Their versatile applications include orthopedic diseases, such as osteoporosis, osteoarthritis, and bone defects; ophthalmic conditions, including glaucoma and diabetic retinopathy; and gynecological disorders, such as premature ovarian insufficiency, ovarian cancer, and endometriosis. These systems target key metabolic abnormalities, such as glycolytic dysregulation, mitochondrial dysfunction, and oxidative stress, which are recognized as central drivers of disease pathogenesis across multiple organ systems. Despite considerable progress, clinical translation remains limited by tissue-specific delivery barriers, interindividual metabolic heterogeneity, and long-term safety concerns within dynamic metabolic networks. Emerging strategies, such as personalized formulations, artificial-intelligence-driven designs, and organ-on-a-chip validation platforms, are being developed to address these challenges. With ongoing interdisciplinary innovation, metabolism-regulating microspheres hold great promise as precise therapeutic modalities for a spectrum of chronic diseases rooted in metabolic imbalance, offering targeted and sustained metabolic correction.

Background:Osteoarthritis (OA) is a chronic degenerative disease primarily characterized by articular cartilage degradation and chondrocyte dysfunction. Mitochondrial impairment and oxidative stress in chondrocytes are pivotal contributors to OA pathogenesis. Emerging evidence suggests that metformin, beyond its role in glucose regulation, exhibits antioxidative and anti-inflammatory properties via activation of AMP-activated protein kinase (AMPK). Nonetheless, how metformin regulates mitochondrial dynamics and autophagy in OA remains to be fully elucidated. Methods:A mouse anterior cruciate ligament transection (ACLT) model and an IL-1β-induced oxidative stress model in human chondrocytes were established. Following metformin administration, a comprehensive assessment was conducted using histological staining, immunohistochemistry, Western blotting, flow cytometry, confocal microscopy, and AMPK siRNA transfection to evaluate the effects of metformin on mitochondrial function, autophagic activity, and oxidative stress in chondrocytes. Results:Metformin markedly improved articular cartilage architecture in ACLT mice and enhanced the stability of the cartilage matrix. It activated AMPK signaling in chondrocytes while suppressing Dynamin-related protein 1 (Drp1) phosphorylation at Ser637, thereby promoting mitochondrial fission and mitophagy. By reducing reactive oxygen species accumulation, restoring mitochondrial membrane potential, and inhibiting NOD-like receptor thermal protein domain associated protein 3 inflammasome activation, metformin effectively mitigated oxidative stress in chondrocytes. AMPK siRNA experiments further demonstrated that the AMPK/Drp1 axis is pivotal for metformin-induced mitochondrial protection and promotion of chondrocyte proliferation. Conclusion:This study demonstrates that metformin delays osteoarthritis progression by activating the AMPK/Drp1 pathway to modulate mitochondrial fission and mitophagy, attenuate oxidative stress, and restore chondrocyte function. These findings provide novel mechanistic insight into the therapeutic potential of metformin in osteoarthritis and highlight mitochondrial dynamics as a promising target for future OA interventions.

Osteoarthritis (OA) is a chronic, progressive degenerative joint disease defined by the degradation of articular cartilage, with pathological involvement of periarticular tissues including the synovium and subchondral bone. Existing conservative interventions for OA are limited to symptomatic relief and cannot reverse established cartilage degeneration, underscoring the critical unmet need to address prevailing clinical treatment bottlenecks. Hydrogel microspheres, as an emerging delivery platform integrating drug delivery capabilities with tissue engineering scaffold functions, hold substantial promise for targeted OA therapy and cartilage repair. Their core beneficial properties include minimally invasive injectability, favorable biocompatibility, sustained drug release capacity, and intelligent responsiveness. This review systematically explores the application of hydrogel microspheres in the treatment of OA and provides a detailed summary of material systems and preparation techniques—covering natural materials, synthetic polymers, and composite/hybrid materials, as well as processes such as emulsion cross-linking, microfluidics, electrospray, photolithography, and 3D printing. This paper places particular emphasis on the modulation of mechanical properties, smart responsive release mechanisms, and strategies to enhance bioactivity. Furthermore, it summarizes various therapeutic strategies supported by hydrogel microspheres, including the precise controlled release of small-molecule drugs, the regulation of endogenous stem cell recruitment and directed differentiation, the targeted delivery of gene therapy drugs, and synergistic treatment modalities. By synthesizing core research advances in this field in recent years and elucidating key technological development directions, this review provides a comprehensive reference for advancing the translation of hydrogel microspheres from basic research to clinical applications in the management of OA.

Abstract Background Autologous and allogeneic bone grafts are primarily used for bone tissue defects; however, they have limitations such as limited supply, donor site morbidity, and immune rejection risks. Therefore, substitute synthetic bone grafts are required. Methods Using low-temperature 3D printing combined with freeze-drying technology, a hierarchically porous PLGA/HA@SeNPs composite scaffold was fabricated by compositing poly(lactic-co-glycolic acid) (PLGA) with hyaluronic acid-modified selenium nanoparticles (HA@SeNPs), enabling sustained immunomodulation and osteogenic activity through its engineered microtopography and bioactive components. Results In vitro evaluations confirmed that the unique microstructure and sustained selenium release from HA@SeNPs synergistically promoted macrophage polarization toward the M2 phenotype, accompanied by enhanced osteogenic differentiation as shown by upregulation of Runx2 and OCN and accelerated matrix mineralization. Implantation into a rat femoral critical-sized defect model resulted in substantially improved bone repair and architectural restoration. Conclusions These findings indicate that the intrinsic physicochemical properties of the PLGA/HA@SeNPs scaffold orchestrate a favorable osteo-immune environment, positioning it as a promising platform for bone regeneration.

Periprosthetic joint infection (PJI) is a major complication following total hip arthroplasty (THA), posing significant diagnostic challenges. This study prospectively evaluated 114 patients from January 2021 to August 2023, including those with PJI and aseptic loosening, using computed tomography (CT) to count enlarged inguinal lymph nodes with a short-axis diameter greater than 5 mm as assessed by two blinded radiologists. Patients with PJI had significantly higher lymph node counts (median 4.5, range 1–13) compared with those with aseptic loosening (median 1, range 0–5). Using a threshold of more than 2.5 enlarged nodes, CT achieved 86.8% sensitivity and 85.5% specificity, with an area under the curve (AUC) of 0.91, which was superior to conventional markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). These findings suggest that CT-based enlarged inguinal lymph node counting is a simple, non-invasive, and accurate method for diagnosing PJI, and may enhance current diagnostic strategies. Trial registration number: No. ChiCTR2100050785.

Renal osteodystrophy is a debilitating complication of chronic kidney disease characterized by deteriorated bone microarchitecture and impaired bone formation, leading to increased fracture risk. Despite the pressing need for anabolic therapies, the cellular mechanisms by which uremic stress compromises osteoprogenitor function remain poorly defined. Here, metabolomic profiling of renal osteodystrophy patient cohorts revealed a profound depletion of circulating betaine. We show that betaine supplementation not only rescued the osteogenic differentiation of bone marrow-derived mesenchymal stem cells challenged with the uremic toxin indoxyl sulfate but also ameliorated skeletal deterioration in a rat model of chronic kidney disease. Mechanistically, we demonstrated that indoxyl sulfate triggered ferroptosis in bone marrow-derived mesenchymal stem cells—characterized by iron-dependent lipid peroxidation and aberrant HMOX1 up-regulation—thereby arresting osteogenesis. Betaine mitigates this ferroptotic stress through a novel post-transcriptional mechanism. Specifically, betaine down-regulated the RNA-binding protein hnRNP A1, preventing the recruitment of the CNOT1 deadenylase complex. This inhibition stabilized Abcg1 mRNA, leading to restored ABCG1 expression. Functional perturbation studies confirmed that the ABCG1–HMOX1 axis was indispensable for the anti-ferroptotic and osteoprotective effects of betaine. Collectively, our findings delineate a Betaine–hnRNP A1/CNOT1–ABCG1–HMOX1 signaling cascade that links metabolic deficiency to ferroptosis-driven osteogenic failure, positioning betaine as a promising anabolic therapeutic strategy for renal osteodystrophy.

Ionizing radiation (IR) is a major cause of accelerated skeletal aging and severe bone loss, primarily by triggering oxidative stress and promoting premature senescence in bone marrow mesenchymal stem cells (BMSCs). This mechanism underscores a critical need for redox-based intervention. Peroxiredoxin 1 (Prdx1), a vital thiol peroxidase and redox sensor, is recognized for its potent anti-oxidative and anti-senescence capabilities. However, the precise function and underlying mechanism of Prdx1 in protecting BMSCs from IR-induced bone loss remain unexplored. Through Single-cell RNA-sequencing (scRNA-seq) and IR-induced bone loss mice model, we found that the Prdx1 expression in BMSCs exhibited a transient elevation in early stage after IR, while its expression was downregulated in late stage after IR. A prdx1-knockout mice (Prdx1KO) was constructed and exhibited aggravated bone loss after IR. Prdx1KO-derived primary BMSCs exhibited elevated oxidative stress and cellular senescence level, confirming a protective role for Prdx1. By high-throughput RNA-sequencing (RNA-seq), transcriptional factor prediction, molecular dynamic simulation, we verified that Prdx1 inhibited BMSCs oxidative stress injury via interacting with Pten and suppressing the Akt/FoxO signaling pathway. A BMSCs-specific E7 affinity peptide modified extracellular vesicle (EV) delivery system E7-EVPrdx1 was constructed to achieve targeted delivery of Prdx1 mRNA to BMSCs. E7-EVPrdx1 effectively suppressed IR-induced oxidative stress injury in vitro. Systemic administration of E7-EVPrdx1 effectively rescued IR-induced bone loss and demonstrated favourable biocompatibility in vivo. Our study identifies Prdx1 as a pivotal redox-regulated target in IR-induced BMSCs injury and introduces E7-EVPrdx1 as a novel, highly efficient, and safe gene therapy strategy for mitigating IR-induced bone loss.