Critical-size bone defects remain a significant clinical challenge. The lack of endogenous stem cells with osteogenic differentiation potential in the defect area, combined with the inflammatory responses induced by scaffold implantation, highlights the need for biomaterials that can deliver stem cells and possess inflammatory regulation properties. In this study, we developed a 3D bioprinted gelatin methacrylate (GelMA) hydrogel scaffold modified with luteolin-loaded ZIF-8 (LUT@ZIF-8) nanoparticles, designed to deliver bone marrow mesenchymal stem cells (BMSCs) to the defect site and release bioactive components that promote osteogenesis and modulate the immune microenvironment. The LUT@ZIF-8/GelMA hydrogel scaffolds demonstrated excellent physical properties and biocompatibility. The sustained release of luteolin and zinc ions from the LUT@ZIF-8 nanoparticles conferred antibacterial, osteoinductive, and inflammatory regulation effects. The immune microenvironment modulated by LUT@ZIF-8/GelMA hydrogel scaffolds facilitated osteogenic differentiation of BMSCs. Furthermore, in vivo experiments confirmed the osteogenic and inflammatory regulation capabilities of the LUT@ZIF-8/GelMA hydrogel scaffolds. In conclusion, the 3D bioprinted LUT@ZIF-8/GelMA hydrogel scaffolds exhibit osteoimmunomodulatory properties, presenting a promising strategy for the treatment of bone defects.

Background: Metal-organic frameworks (MOFs) are hybrid materials composed of metal ions or clusters and organic ligands that spontaneously assemble via coordination bonds to create intramolecular pores, which have recently been widely used in biomedicine due to their porosity, structural, and functional diversity. They are used in biomedical applications, including biosensing, drug delivery, bioimaging, and antimicrobial activities. Our study aims to provide scholars with a comprehensive overview of the research situations, trends, and hotspots in biomedical applications of MOFs through a bibliometric analysis of publications from 2002 to 2022.Methods: On 19 January 2023, the Web of Science Core Collection was searched to review and analyze MOFs applications in the biomedical field. A total of 3,408 studies published between 2002 and 2022 were retrieved and examined, with information such as publication year, country/region, institution, author, journal, references, and keywords. Research hotspots were extracted and analyzed using the Bibliometrix R-package, VOSviewer, and CiteSpace.Results: We showed that researchers from 72 countries published articles on MOFs in biomedical applications, with China producing the most publications. The Chinese Academy of Science was the most prolific contributor to these publications among 2,209 institutions that made contributions. Reference co-citation analysis classifies references into 8 clusters: synergistic cancer therapy, efficient photodynamic therapy, metal-organic framework encapsulation, selective fluorescence, luminescent probes, drug delivery, enhanced photodynamic therapy, and metal-organic framework-based nanozymes. Keyword co-occurrence analysis divided keywords into 6 clusters: biosensors, photodynamic therapy, drug delivery, cancer therapy and bioimaging, nanoparticles, and antibacterial applications. Research frontier keywords were represented by chemodynamic therapy (2020–2022) and hydrogen peroxide (2020–2022).Conclusion: Using bibliometric methods and manual review, this review provides a systematic overview of research on MOFs in biomedical applications, filling an existing gap. The burst keyword analysis revealed that chemodynamic therapy and hydrogen peroxide are the prominent research frontiers and hot spots. MOFs can catalyze Fenton or Fenton-like reactions to generate hydroxyl radicals, making them promising materials for chemodynamic therapy. MOF-based biosensors can detect hydrogen peroxide in various biological samples for diagnosing diseases. MOFs have a wide range of research prospects for biomedical applications.

One-carbon metabolism is a universal metabolic process that mediates the transfer of one-carbon units for purine and thymidine synthesis. One-carbon metabolism has been found to be dysregulated in various cancer types due to its role in production of purine and pyrimidine nucleotides, epigenetic program, and redox homeostasis. One-carbon metabolism is composed a network of one-carbon metabolic enzymes. Disturbing the expression and enzymatic activity of these one-carbon metabolic enzymes could lead to fluctuations of metabolites in the tumor microenvironment. Serine hydroxymethyltransferases (SHMTs) and methylenetetrahydrofolate dehydrogenases (MTHFDs) are gradually recognized as important one-carbon metabolic enzymes for regulating tumor initiation and development, representing potential therapeutic targets for anti-tumor strategies. In the review, we primarily focused on the role of SHMTs and MTHFDs in cancer. Several inhibitors targeting MTHFDs and SHMTs have exert its potential to decrease tumor burden and inhibit tumor proliferation, highlighting the potential of targeting one-carbon metabolic enzymes for anti-cancer strategies.

Oral squamous cell carcinoma (OSCC) is a malignant neoplasm with high mortality and morbidity. The role of circRNA and its molecular mechanism in OSCC remains largely unknown. The study aims to explore the role of a novel circular RNA (circLDLRAD3) in OSCC and its underlying mechanism. PCR and fluorescence in situ hybridization were used to explore the expression features of circLDLRAD3 in OSCC. The effects of circLDLRAD3 on the behaviour of OSCC were investigated using CCK‐8, colony formation assay, transwell and animal experiments. Bioinformatics analysis along with dual luciferase reporter assay and RIP assay were used to reveal the interaction between circLDLRAD3, miR‐558 and Smad4. It was revealed that circLDLRAD3 exhibited low expression status in OSCC. CircLDLRAD3 inhibits proliferation, migration, and invasion of OSCC cells both in vitro and in vivo. Mechanistically, circLDLRAD3 could bind with miR‐558 to positively regulate its target gene Smad4 expression. Rescue experiments further confirmed both miR‐558 overexpression and Smad4 knockdown could reverse the influence of circLDLRAD3 on OSCC phenotypes. Moreover, circLDLRAD3 regulate the TGF‐β signalling pathways to influence EMT through miR‐558/Smad4 axis. Our study found that circLDLRAD3 is downregulated in OSCC and verified its tumour suppressor function and mechanism in OSCC through sponging miR‐558 to regulate miR‐558/Smad4/TGF‐β axis. The characterization of such regulating network uncovers an important mechanism underlying OSCC progression, which could provide promising targets targeted therapy strategies for OSCC in the future.