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.

Objectives: Osteosarcoma was the most popular primary malignant tumor in children and adolescent, and the 5-year survival of osteosarcoma patients gained no substantial improvement over the past 35 years. This study aims to explore the role of lipid metabolism in the development and diagnosis of osteosarcoma.Methods: Clinical information and corresponding RNA data of osteosarcoma patients were downloaded from TRGET and GEO databases. Consensus clustering was performed to identify new molecular subgroups. ESTIMATE, TIMER and ssGSEA analyses were applied to determinate the tumor immune microenvironment (TIME) and immune status of the identified subgroups. Functional analyses including GO, KEGG, GSVA and GSEA analyses were conducted to elucidate the underlying mechanisms. Prognostic risk model was constructed using LASSO algorithm and multivariate Cox regression analysis.Results: Two molecular subgroups with significantly different survival were identified. Better prognosis was associated with high immune score, low tumor purity, high abundance of immune infiltrating cells and relatively high immune status. GO and KEGG analyses revealed that the DEGs between the two subgroups were mainly enriched in immune- and bone remodeling-associated pathways. GSVA and GSEA analyses indicated that, lipid catabolism downregulation and lipid hydroxylation upregulation may impede the bone remodeling and development of immune system. Risk model based on lipid metabolism related genes (LMRGs) showed potent potential for survival prediction in osteosarcoma. Nomogram integrating risk model and clinical characteristics could predict the prognosis of osteosarcoma patients accurately.Conclusion: Expression of lipid-metabolism genes is correlated with immune microenvironment of osteosarcoma patients and could be applied to predict the prognosis of in osteosarcoma accurately.

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.

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.