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A tantalum-containing zirconium-based metallic glass with superior endosseous implant relevant properties (BMSC)

ABSTRACT: Tantalum (Ta) metal is well known for its ideal corrosion resistance and biological effects as endosseous implants. However, the metal has a elastic modulus as high as 186GPa which is not comparable to the natural bone (10-40GPa), and it also has a relative high cost. Here, to fully exploit the advantages of Ta as endosseous implants, a small amount of Ta (as low as 3 at.%) was successfully added into a zirconium-based metallic glass (MG) to generate an advanced functional endosseous implant, Zr58Cu25Al14Ta3 MG, with superior comprehensive properties. Upon carefully dissecting the surface chemistry and atomic structure, the results show that amorphization of Ta enable the uniform distribution in material surface, leading to a significantly improved chemical stability and extensive material-cell contact regulation. Systematical analyses on the immunological, angiogenesis and osteogenesis capability of the material is carried out by utilizing the next-generation sequencing, revealing that Zr58Cu25Al14Ta3 MG can regulate angiogenesis through VEFG signaling pathway and osteogenesis via BMP signaling pathway. Animal experiment further confirms a sound osseointegration of Zr58Cu25Al14Ta3 MG in achieving better bone-implant-contact and inducing faster peri-implant bone formation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE252669 | GEO | 2024/05/29

REPOSITORIES: GEO

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Project description:Rationale：Poor peri-implant osseointegration of dental implants in patients with type II diabetes has become a major clinical challenge in recent years. MSC (Mesenchymal stem cell)-derived exosomes may play an important role in peri-implant osseointegration, but the mechanism remains unclear. Enhancing the therapeutic effect of MSC-derived exosomes and exploring the potential mechanism can help provide a new therapeutic strategy to improve the clinical outcome of dental implant restorations in patients with type II diabetes. Methods：The exosomes derived from hypoxia (Hypo-exos) or normoxia (Nor-exos) preconditioned bone marrow mesenchymal stem cells (BMSCs) were co-cultured with BMSCs and human umbilical vein endothelial cells (HUVECs). The effect of exosomes on BMSCs cell proliferation was detected by CCK-8 assay and EdU assay, and the effect on angiogenesis ability of HUVECs was detected by wound healing assay, transwell migration assay, tube formation assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. A diabetic rat dental implant model was also established and the effect of exosomes on implant osseointegration was evaluated through micro-CT scanning and histological analysis. The differentially expressed miRNAs between Hypo-exos and Nor-exos were identified by high-throughput miRNA sequencing. Subsequently, the target genes and their roles in regulating angiogenesis were predicted and analyzed by bioinformatics analysis and dual luciferase reporter assay. Results：In vitro experiments indicated that hypoxia preconditioning could elevate exosome production and promote cell proliferation of BMSCs and angiogenesis of HUVECs. Moreover, Hypo-exos promoted peri-implant osteogenesis in rats with diabetes. Further investigation revealed the vital involvement of the miR-106b-5p/HIF-1α axis in promoting peri-implant osseointegration. Conclusion: Exosomes derived from hypoxia-preconditioned BMSCs could improve the peri-implant osseointegration in rats with diabetes by promoting cell proliferation and angiogenesis, and the miR-106b-5p/ HIF-1α axis could be the underlying mechanism.

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A tantalum-containing zirconium-based metallic glass with superior endosseous implant relevant properties (BMSC)

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