Angiogenesis-osteogenesis coupling and anti-osteoclastogenesis zoledronate intermixed calcium silicate metal-organic/inorganic hybrid coating on biodegradable zinc-based intramedullary nails for osteoporotic fracture healing

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials Pub Date : 2024-10-11 DOI:10.1016/j.bioactmat.2024.09.041

Junyu Qian , Haotian Qin , En Su , Jiaming Hou , Hui Zeng , Tianbing Wang , Deli Wang , Guojiang Wan , Yingqi Chen

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引用次数: 0

Abstract

Osteoporotic (OP) fractures remain a tough clinical challenge owing to their impaired healing outcome, which requires novel biomaterials with osteogenicity for effective healing. Metallic zinc (Zn) is attracting increasing attention for biodegradable intramedullary nails (IMNs) for OP fracture healing thanks to their comprehensive mechanical properties, biosafety, and bioactivity. However, the multiple biofunctions required for OP fracture healing have not been fully met by Zn. Herein, a zoledronate (ZA)-mediated calcium-zinc silicate (Ca(Zn)Si) metal-organic/inorganic hybrid coating was fabricated on Zn-based IMN by coordination chemistry driven via interactions between ZA and Ca²⁺/Zn²⁺ as well as in-situ directional growth of Ca(Zn)Si phase. The ZA&Ca(Zn)Si hybrid coating exhibited a homogeneous micro/nanostructure with a granular morphology, which prevented premature fracture failure of IMN in rat femur by ameliorating corrosion mode and decreasing degradation rate of the Zn matrix. More importantly, this hybrid coating enabled sustained release of Zn²⁺/Ca²⁺/Si⁴⁺ and ZA in the long term, achieving a remarkable effect on vascularized bone regeneration. The coated IMN enhanced angiogenesis–osteogenesis coupling through autocrine and paracrine effects between endothelial cells and bone marrow mesenchymal stem cells. Osteoclastogenesis was repressed by Zn²⁺ and ZA. This approach offers a new strategy for surface-engineering of biodegradable metals for bone fracture healing.

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用于骨质疏松性骨折愈合的可生物降解锌基髓内钉上的血管生成-骨生成耦合及抗骨细胞生成唑来膦酸钙混合硅酸钙金属-有机/无机杂化涂层

骨质疏松性骨折（OP）由于愈合效果不佳，仍然是一项严峻的临床挑战，这就需要具有成骨性的新型生物材料来实现有效愈合。金属锌（Zn）凭借其全面的机械性能、生物安全性和生物活性，在用于骨质疏松性骨折愈合的可生物降解髓内钉（IMNs）方面吸引了越来越多的关注。然而，锌尚未完全满足 OP 骨折愈合所需的多种生物功能。在此，通过唑来膦酸盐（ZA）与 Ca2+/Zn2+ 之间的相互作用以及 Ca(Zn)Si 相的原位定向生长，在 Zn 基 IMN 上制造了由唑来膦酸盐（ZA）介导的钙锌硅酸盐（Ca(Zn)Si）金属有机/无机杂化涂层。ZA&Ca(Zn)Si混合涂层呈现出均匀的微/纳米结构，具有颗粒状形态，通过改善腐蚀模式和降低锌基质的降解率，防止了大鼠股骨中IMN的过早断裂失效。更重要的是，这种混合涂层能长期持续释放 Zn2+/Ca2+/Si4+ 和 ZA，对血管骨再生有显著效果。涂层 IMN 通过内皮细胞和骨髓间充质干细胞之间的自分泌和旁分泌效应，增强了血管生成-骨生成耦合。Zn2+和ZA抑制了破骨细胞的生成。这种方法为用于骨折愈合的生物可降解金属表面工程提供了一种新策略。

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来源期刊

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.