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Abstract Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.

Abstract Purpose Currently, postoperative wound infection and poor healing of total knee arthroplasty have been perplexing both doctors and patients. We hereby innovatively invented a new dressing system to reduce the incidence of postoperative wound complications. Methods We enrolled 100 patients who received primary unilateral total knee arthroplasty and then applied the new dressing system. The data collected included the number of dressing changes, postoperative hospital stay, Visual Analogue Scale score (VAS), the Knee Society Score (KSS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), ASEPSIS scores, The Stony Brook Scar Evaluation Scale (SBSES), wound complications, dressing cost, the frequency of shower and satisfaction. Subsequently, a statistical analysis of the data was performed. Results Our findings demonstrated the average number of postoperative dressing changes was 1.09 ± 0.38, and the average postoperative hospital stay was 3.72 ± 0.98 days. The average cost throughout a treatment cycle was 68.97 ± 12.54 US dollars. Collectively, the results of VAS, KSS, and KOOS revealed that the pain and function of patients were continuously improved. The results of the four indexes of the ASEPSIS score were 0, whereas the SBSES score was 3.58 ± 0.52 and 4.69 ± 0.46 at two weeks and one month after the operation, respectively. We observed no wound complications until one month after the operation. Remarkably, the satisfaction rate of the patients was 91.85 ± 4.99% one month after the operation. Conclusion In this study, we invented a new dressing system for surgical wounds after total knee arthroplasty and further confirmed its clinical feasibility and safety. Chinese clinical trial registry ChiCTR2000033814, Registered 13/ June/2020.

Infected bone defects (IBDs) remains a challenging problem for orthopedists. Clinically, routine management for IBDs has two stages: debridement and systematic antibiotics administration to control infection, and secondary grafting to repair bone defects. Whereas the efficacy is not satisfactory, because the overuse of antibiotics may lead to systemic toxicity, and the emergence of drug-resistant bacteria, as well as the secondary surgery would cause additional trauma and economic burden to the patients. Therefore, it is imperative to develop a novel scaffold for one-stage repair of IBDs. In this study, vancomycin (Van) was encapsulated into poly(lactic co-glycolic acid) (PLGA) microspheres through the double emulsion method, which were then loaded into the additively-manufactured porous tantalum (AM-Ta) through gelatin methacryloyl (GelMA) hydrogel to produce the composite Ta/GelMA hydrogel (Gel)/PLGA/vancomycin(Van) scaffolds for repairing IBDs. Physiochemical characterization of the newly-developed scaffold indicated that the releasing duration of Van was over 2 weeks. Biological experiments indicated good biocompatibility of the composite scaffold, as well as bacteriostasis and osteointegration properties, which showed great potential for clinical application. The construction of this novel scaffold would provide new sight into the development of orthopaedic implants, shedding a novel light on the treatment of IBDs.

Anterior cruciate ligament reconstruction (ACLR) often fails due to the inability of tendon-bone integration to regenerate normal tissues and formation of fibrous scar tissues in the tendon-bone interface. Cartilage fragments and exosomes derived from bone mesenchymal stromal cells (BMSCs-Exos) can enhance enthesis healing. Nevertheless, the effects on the tendon-bone healing of ACLR remain unknown. This study found that BMSCs-Exos can promote the proliferation of chondrocytes in cartilage fragments, and activated the expression of chondro-related genes SOX9 and Aggrecan. The optimal effect concentration was 1012 events/uL. Besides, BMSCs-Exos could significantly upregulated the expression of BMP7 and Smad5 in cartilage fragments, and further enhanced the expression of chondrogenic genes. Moreover, this study established a rat model of ACLR and implanted the BMSCs-Exos/cartilage fragment complex into the femoral bone tunnel. Results demonstrated that the mean diameters of the femoral bone tunnels were significantly smaller in the BE-CF group than those in the CF group (p = 0.038) and control group (p = 0.007) at 8 weeks after surgery. Besides, more new bone formation was observed in the femoral tunnels in the BE-CF group, as demonstrated by a larger BV/TV ratio based on the reconstructed CT scans. Histological results also revealed the regeneration of tendon-bone structures, especially fibrocartilage. Thus, these findings provide a promising result that BMSCs-Exos/cartilage fragment complex can prevent the enlargement of bone tunnel and promote tendon-bone healing after ACLR, which may have resulted from the regulation of the BMP7/Smad5 signaling axis.

Background Charcot joint disease is a rare neurogenic lesion of the joint characterized by progressive joint destruction with dislocation or subluxation. However, whether a joint replacement should be performed for severe joint damage is controversial. Case presentation This paper reports a case of severe Charcot joint disease with a large bone defect that was treated with arthroplasty assisted by a customized 3D‐printed porous tantalum. The patient was admitted to the hospital with a 9‐year history of bilateral knee pain that had aggravated in the past 2 months. Radiography showed osteogeny and sclerosis in both knees, free bone fragments, heterotopic ossification, new bone, and osteophyte formation, irregular margins, apparent narrowing of joint space, and severe joint damage (Anderson Orthopedic Research Institute classification type III). Based on the present illness, history, imaging, and laboratory examination, Charcot joint disease was confirmed. Conservative treatment has been reported in the literature. There are limited reports on the surgical treatment of severe Charcot joint disease. We followed up with the patient for a year after the operation, and the imaging and clinical evaluation results were good. Postoperative X‐ray examinations showed good alignment of force lines, good joint space, and no evidence of loosening. The patient was mobile and did not need crutches. Conclusions Through accurate surgical evaluation and preparation of 3D‐printed porous tantalum implants, severe AORI classification type III Charcot joint disease can effectively restore the range of motion of the knee joint, the lower limb alignment, and finally achieve good functional results of walking without crutches.

Abstract Background Whether there was clinical superiority for the single‐radius prosthesis over the multi‐radius prothesis in total knee arthroplasty (TKA) still remains to be clarified. We updated a meta‐analysis including prospective randomized controlled trials (RCTs) to compare the clinical prognosis of patients receiving single‐radius TKA (SR‐TKA) or multi‐radius TKA (MR‐TKA). Methods We searched the databases of PubMed, Web of Science, EMBASE, Cochrane Library, MEDLINE for eligible RCTs. Two reviewers evaluated the study quality according to the Risk of Bias tool of the Cochrane Library and extracted the data in studies individually. The extracted data included the baseline data and clinical outcome. The baseline data include the author's name, country, and year of included studies, the name of knee prosthesis used in studies, sample size, follow‐up time, and BMI of patients. The clinical data comprised primary indicators including postoperative knee range of motion (ROM), sit‐to‐stand rest, severe postoperative scorings, such as visual analog scale (VAS), American Knee Society knee score (AKS), Oxford knee scoring (OKS), and SF‐36 Quality of Life Scale, as well as various secondary indicators of complications including anterior knee pain, postoperative infection, aseptic prosthesis loosening, and prosthesis revision. The data analysis was performed using Review Manager 5.3 software and STATA 12.0. The sensitivity analysis was performed using STATA 12.0. Results A total of 13 RCTs, along with 1720 patients and 1726 knees, were finally included in our present meta‐analysis. We found that patients in SR‐TKA group performed better in the sit‐to‐stand test (OR = 1.89, 95% CI: 1.05–3.41, p = 0.03) and satisfaction evaluation (OR = 3.27, 95% CI: 1.42–7.53, p = 0.005), which were only evaluated in two included RCTs. While no significant difference was found between SR‐TKA and MR‐TKA groups in terms of postoperative ROM, VAS scoring, AKS scoring, SF‐36 scoring, OKS scoring, and various complications including anterior knee pain, postoperative infection, aseptic prosthesis loosening, and prosthesis revision. Conclusion In conclusion, our present meta‐analysis indicated that SR implants were noninferior to MR implants in TKA, and SR implants could be an alternative choice over MR implants, since patients after SR‐TKA felt more satisfied and performed better in the sit‐to‐stand test, with no significant difference in complications between SR‐TKA and MR‐TKA groups. While more relevant clinical trials with long‐term follow‐up time and specific tests evaluating the function of knee extension mechanism should be carried out to further investigate the clinical performance of SR implants.

Abstract Osteosarcoma is the most common malignant tumor in children and adolescents and its diagnosis and treatment still need to be improved. Necroptosis has been associated with many malignancies, but its significance in diagnosing and treating osteosarcoma remains unclear. The objective is to establish a predictive model of necroptosis-related genes (NRGs) in osteosarcoma for evaluating the tumor microenvironment and new targets for immunotherapy. In this study, we download the osteosarcoma data from the TARGET and GEO websites and the average muscle tissue data from GTEx. NRGs were screened by Cox regression analysis. We constructed a prediction model through nonnegative matrix factorization (NMF) clustering and the least absolute shrinkage and selection operator (LASSO) algorithm and verified it with a validation cohort. Kaplan–Meier survival time, ROC curve, tumor invasion microenvironment and CIBERSORT were assessed. In addition, we establish nomograms for clinical indicators and verify them by calibration evaluation. The underlying mechanism was explored through the functional enrichment analysis. Eight NRGs were screened for predictive model modeling. NRGs prediction model through NMF clustering and LASSO algorithm was established. The survival, ROC and tumor microenvironment scores showed significant statistical differences among subgroups (P

Despite the widespread application of Ti6Al4V and tantalum (Ta) in orthopedics, bioinertia and high cost limit their further applicability, respectively, and tremendous efforts have been made on the Ti6Al4V-Ta alloy and Ta coating to address these drawbacks. However, the scaffolds obtained are unsatisfactory. In this study, novel high-interface-strength Ti6Al4V-based porous Ta scaffolds were successfully manufactured using Laser Powder Bed Fusion for the first time, in which porous Ta was directly manufactured on a solid Ti6Al4V substrate. Mechanical testing revealed that the novel scaffolds were biomechanically compatible, and the interfacial bonding strength was as high as 447.5 MPa. In vitro biocompatibility assay, using rat bone marrow mesenchymal stem cells (r-BMSCs), indicated that the novel scaffolds were biocompatible. Alkaline phosphatase and mineralized nodule determination demonstrated that the scaffolds favored the osteogenic differentiation of r-BMSCs. Moreover, scaffolds were implanted into rabbits with femur bone defects, and imaging and histological evaluation identified considerable new bone formation and bone ingrowth, suggesting that the scaffolds were well integrated with the host bone. Overall, these results demonstrated good mechanical compatibility, biocompatibility, and osteointegration performance of the novel Ti6Al4V-based porous Ta scaffold, which possesses great potential for orthopedic clinical applications.

The inflammatory microenvironment created by macrophages has been proven critical for bone regeneration. Both tantalum nanoparticles and micron particles have been applied to bone tissue engineering and have achieved good efficacy, but their effects on immune microenvironment remain unclear. Herein, we explored the different effects between nano- and micro-tantalum particles on the innate immunity of macrophages in vitro and in vivo. RAW 264.7 ​cells were co-cultured with nano- and micro-tantalum particles under inflammatory conditions to evaluate the effects on the morphology and behavior of macrophages. Air pouch model was used to evaluate the material-induced macrophage polarization in vivo. Compared to the tantalum micron particles (TaMPs), the morphology of macrophages was more similar to the M2 phenotype in co-culture with tantalum nanoparticles (TaNPs). At the same time, the TaNPs could also decrease the gene expression of interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α), inducible nitric oxide synthase (iNOS), and increase the expression of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10). Furthermore, the air pouch model showed more M2 macrophage infiltration under the intervention of TaNPs. Our findings demonstrated that TaNPs could significantly increase the polarization of M2 macrophages and decrease the macrophage polarization to the M1 phenotype under the inflammatory microenvironment, showing better immunomodulatory properties.

Bone nonunion or delayed union, caused by stripping or injuring of periosteum, is the most common sequelae of segmental bone defects. The preservation of periosteum, or the use of periosteal grafts, can significantly improve the integration of bone graft, speeding up the process of bone reconstruction. However, in most cases, periosteum cannot be preserved with bioactivity. Thus, it is pivotal to develop artificial periosteum. In this study, artificial periosteum of PLGA/MgO/Quercetin was prepared by electrospinning. PLGA/MgO/Quercetin membranes were shown to have a highly porous surface and microstructure, as observed by scanning electron microscopy. Along with excellent biocompatibility, PLGA/MgO/Quercetin membranes promoted cell proliferation and migration, as well as osteogenic differentiation of BMSCs (Bone marrow mesenchymal stem cells) in a dose-dependent manner through the activation of Wnt/β-Catenin pathway. The PLGA/MgO/Quercetin membranes, with an appropriate concentration of quercetin (

Segmental bone defects, accompanied by periosteum stripping or injury, usually lead to delayed bone union or nonunion, which have challenged orthopedic surgeons. The periosteum, which provides essential blood supply and initial stem cells for bone tissue, plays an important role in the repair of bone defects. The reconstruction of the destroyed periosteum has attracted the attention of researchers exploring more satisfactory therapies to repair bone defects. However, periosteum-like biomaterials have yet to meet the clinical requirements and resolve this challenging problem. In this study, we manufactured a nanofiber periosteum replacement based on poly-ε-caprolactone (PCL), in which tantalum nanoparticles (TaNPs) and nanoscale magnesium oxide (MgO) were introduced to enhance its osteogenic and angiogenic ability. The results of in vitro experiments indicated that the PCL/Ta/MgO periosteum replacement, with excellent cytocompatibility, promoted the proliferation of both bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs). Furthermore, the incorporation of TaNPs and nano-MgO synergistically enhanced the osteogenic differentiation of BMSCs and the angiogenic properties of EPCs. Similarly, the results of in vivo experiments from subcutaneous implantation and critical-sized calvarial defect models showed that the PCL/Ta/MgO periosteum replacement combined the osteogenesis and angiogenesis abilities, promoting vascularized bone formation to repair critical-sized calvarial defects. The results of our study suggest that the strategy of stimulating repairing bone defects can be achieved with the periosteum repaired in situ and that the proposed periosteum replacement can act as a bioactive medium to accelerate bone healing.

BackgroundsPostoperative wound complication is a major risk factor for the development of Periprosthetic joint infection. We innovatively invented a new dressing system to reduce the occurrence of postoperative wound complications and improve the quality of life of patients after total hip arthroplasty.MethodsA total of 120 patients who underwent primary unilateral total hip arthroplasty were enrolled in this study. The data collected included the number of dressing changes, costs of the dressings, postoperative hospital stay, The Visual Analogue Scale (VAS) score, The Harris Hip Score (HHS), ASEPSIS score, The Stony Brook Scar Evaluation Scale (SBSES), wound complications, the frequency of showers and satisfaction. Data were statistically analyzed.ResultsThe average number of dressing changes was 0.74 ± 0.46, while the average postoperative hospital stay was 3.67 ± 0.97 days. The average cost of the new dressings throughout a treatment cycle was 57.42 ± 15.18 dollars. The VAS score decreased from 5.63 ± 1.09 before the operation to 0.88 ± 0.54 one month after the operation. The HHS score increased from 70.18 ± 7.84 before the operation to 80.36 ± 4.08 one month after the operation. The results of the four indexes of the ASEPSIS score were all 0. The SBSES score was 3.55 ± 0.61 at two weeks after the operation, and 4.38 ± 0.71 at one month after the operation. No wound complications were recorded until one month after the operation when the satisfaction rate was 92.53 ± 3.62%.ConclusionIn this study, we have invented a new dressing system for surgical wounds after total hip arthroplasty and confirmed its efficacy.Chinese Clinical Trial RegistryChiCTR2000033822, Registered 13/ June/2020

PurposeWe devised a novel dressing system to accelerate the recovery after total knee arthroplasty (TKA). The purpose of this study was to assess the clinical outcomes and economic expenses of the new dressing system.MethodsIn this randomized and controlled trial, we enrolled 98 patients who underwent the first unilateral TKA between September 2020 and June 2021. The patients were randomly assigned to one of two groups: the intervention (the new dressing system group) or the control (the traditional gauze dressing) group. We gathered and evaluated patient data including age, gender, body mass index, surgical side, number of dressing changes, post-operative hospital stay, dressing-related expense, satisfaction, pain and function scores, wound scores and wound-related complications.ResultsThe number of dressing changes and post-operative hospital stay in the intervention group were significantly less than in the control group (p = 0.000, p = 0.002). Satisfaction in the intervention group was significantly higher than in the control group's (p = 0.000). There were no significant differences between the two groups in dressing-related expense, pain and function scores. During the one month follow-up, the intervention group's Stony Brook Scar Evaluation Scale (SBSES) was considerably higher than the control group's (p = 0.012).ConclusionThe new dressing system can reduce the number of dressing changes and post-operative hospital stays while increasing patient satisfaction with no difference in medical costs in TKA. This wound dressing system has potential for application in TKAClinical Trial Registrationhttps://clinicaltrials.gov, identifier ChiCTR2000033814.

Osteoarthritis is a chronic degenerative joint disease and its signs of progress mainly attribute to the significant increase of joint friction and the destruction of articular cartilage. Combined cartilage repair and joint lubrication may be a feasible strategy for the treatment of osteoarthritis. In this study, the hydroxypropyl chitin (HPCH)/hyaluronic acid (HA) hydrogel, prepared by physical mixing of HA and HPCH, was designed to be a new bio-lubricant and a chondroprotective agent for osteoarthritis treatment. HA release in HPCH/HA hydrogel was more durable and stable and in vitro experiments showed that HPCH/HA hydrogel could promote the synthesis of the extracellular matrix of chondrocytes. Additionally, HPCH/HA hydrogel could delay the progression of osteoarthritis in DMM-induced osteoarthritis mouse model. To sum up, HPCH/HA hydrogel developed herein can achieve the dual function of well lubrication of joints and protection of cartilage and has the clinical potential as synergetic treatment of osteoarthritis.

BackgroundAugmented reality and mixed reality have been used to help surgeons perform complex surgeries. With the development of technology, mixed reality (MR) technology has been used to improve the success rate of complex hip arthroplasty due to its unique advantages. At present, there are few reports on the application of MR technology in total knee arthroplasty. We presented a case of total knee arthroplasty with the help of mixed reality technology.Case PresentationWe presented a case of a 71-year-old woman who was diagnosed with bilateral knee osteoarthritis with varus deformity, especially on the right side. After admission, the right total knee arthroplasty was performed with the assistance of MR technology. Before the operation, the three-dimensional virtual model of the knee joint of the patient was reconstructed for condition analysis, operation plan formulation, and operation simulation. During the operation, the three-dimensional virtual images of the femur and tibia coincided with the real body of the patient, showing the osteotomy plane designed before the operation, which can accurately guide the completion of osteotomy and prosthesis implantation.ConclusionsAs far as we know, this is the first report on total knee arthroplasty under the guidance of mixed reality technology.

Relevant research shows teachers’ “psychological power” plays a more essential role in promoting their professional development compared with the powers provided by various external factors, and it is therefore held that exploring college English teachers’ individual psychological power is of great significance. To this end, this study investigated college English teachers’ psychological empowerment (CETPE) via the development and validation of CETPE’s scale. Based on our literature review on psychological empowerment and analysis of teachers professional development’s status quo, we made a working definition of CETPE as a system involving perception of their occupation, sense of competence, experiencing of autonomy, judgment of their impact and understanding of their status. In our study, firstly the literature review and the interview with 17 college English teachers were adopted to conceptualize the dimensions of CETPE, and an exploratory factor analysis of data was conducted from 227 college English teachers and then the subsequent confirmatory factor analysis of data collected from another sample of 1030 generated 15 items belonging to five factors. The findings reveal that CETPE is systematically composed of teachers’ positive perception and experience of work meaningfulness, teaching autonomy, occupational competence, professional impact and social status. This study provides a new path for teachers’ professional development via strengthening their intrinsic driving force and thus helps improve the college English teaching effects.

Introduction: With the development of photothermal technology, the appearance of composite photothermal hydrogels has increased the selectivity of treating infectious skin defects. However, how to design composite photothermal hydrogel with better antibacterial performance, reduce the resistance rate of bacteria, and the damage rate of normal tissue still needs further study.Methods: The Prussian blue and tannic acid were loaded on polyacrylamide hydrogels. Characterization of DLS, Zeta potential, UV absorption spectrum, hydrogel swelling rate, scanning electronic microscopic, drug release profile, photothermal properties, in vitro cytocompatibility, and antibacterial properties. Experiments were measured by skin defect repair, antibacterial detection, and histological staining experiments.Results: The polyacrylamide hydrogel with photothermal effect and controllable release of tannic acid was successfully prepared. The hydrogel has strong light transmittance and adhesion, and the swelling rate can reach 600%, which improves the self-cleaning ability. SEM results showed the porous structure of hydrogels, promoting cell growth. Through photothermal switches, the composite hydrogel represented adjustable and controllable drug release ability. Combined with the synergistic antibacterial effect of tannic acid, this further enhanced the antibacterial ability and reduced the probability of antibiotic resistance. The in vitro and in vivo experiments showed the hydrogel had good biocompatibility and excellent antibacterial properties, which could promote the repair of infectious skin defects in SD rats.Conclusion: We fabricated a hydrogel with a triggering drug release rate, alleviating heat damage, transparent morphology, mechanical stability, strong adhesion, good biocompatibility, and synergistic antibacterial ability, which presents new treatment options for infectious skin defect repair.

Multiple gene-driven programmed cell death 1 ligand 1 (PD-L1)-expressing non-small-cell lung cancer (NSCLC) is very rare. Previous studies have shown that patients with NSCLC with anaplastic lymphoma kinase (ALK) gene rearrangement rarely benefit from PD-L1 inhibitors. Besides the secondary mutations in ALK gene, other mechanisms might contribute to tumor resistance to ALK tyrosine kinase inhibitors (ALK-TKIs). Herein, we present a case of PD-L1-overexpressing lung adenocarcinoma that harbors both EML4-ALK gene rearrangement and BRAF mutation. In particular, a second molecular analysis after resistance to first- and second-generation ALK-TKIs revealed a high PD-L1 expression and tumor mutation burden. Therefore, treatment with nivolumab monotherapy, an anti-PD-1 inhibitor, was started and the patient achieved complete remission. This case report suggested that PD-1 inhibitors might be an effective treatment option for patients with multiple gene-driven PD-L1-expressing NSCLC harboring ALK gene rearrangement.

A loess stratum was selected as the research object, assuming that the slurry diffuses in a hemispherical shape during secondary grouting. Based on the unified strength theory describing the failure characteristics of loess and the critical condition of bolt shear failure, the critical pressure value of the secondary grouting in loess strata was determined theoretically. The reliability of the theoretical analysis was verified by the numerical modeling realizing the large deformation of formation and the dynamic injection of slurry. The critical grouting pressure of 821.80 kPa of theoretical calculation was obtained. Comparing the results of the numerical simulation analysis, it was found that the critical grouting pressure calculated using the theoretical equation had a safety index of 1.14. Bounded by βu (the ratio of expansion radius RP of soil plastic zone to the expansion radius Ru of the slurry) equal to 2.65, the water pressure at the grouting port is the main factor affecting the upper limit of critical grouting pressure when it is less than 2.65, and the effective internal friction angle of soil layer is the main factor when it is greater than 2.65. The influence of matric suction on the upper limit of the critical grouting pressure can be ignored. [ABSTRACT FROM AUTHOR]

Osteosarcoma has been the most common malignant bone tumor in children and adolescents, while the 5-y survival of osteosarcoma patients gained no significant improvement over the past decades. This study aimed to explore the role of ferroptosis-related genes (FRGs) in the development and prognosis of osteosarcoma. The datasets of osteosarcoma patients including RNA sequencing data and clinical information were acquired from the TRGET and Gene Expression Omnibus (GEO) databases. The identification of molecular subgroups with different FRG expression patterns was achieved through nonnegative matrix factorization (NMF) clustering. The prognostic model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analysis. The ESTIMATE algorithm was applied for determining the stromal score, immune score, ESTIMA score, and tumor purity of osteosarcoma patients. Functional analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were conducted to explore the underlying mechanisms in the development and prognosis of osteosarcoma. Two molecular subgroups with different FRGs expression patterns were identified. The molecular subgroups with higher immune score and more active immune status showed better prognostic survival. On the basis of FRGs, a prognostic model and a nomogram integrating clinical characteristics were constructed and their prediction efficiency for osteosarcoma prognosis were well validated. Gene functional enrichment analysis showed that these differentially expressed FRGs were mainly enriched in immunity-related signaling pathways, indicating that FRGs may affect the development and prognosis of osteosarcoma by regulating the immune microenvironment. The expression profiles of FRGs were closely related to the immunity status and prognostic survival of osteosarcoma patients. The interaction between ferroptosis and immunity in the development of osteosarcoma could provide a new insight into the exploration of molecular mechanisms and targeted therapies of osteosarcoma patients. [ABSTRACT FROM AUTHOR]