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通过呈现三功能肽赋予植入物表面增强的血管生成和骨整合能力。

Endowing implants surface with enhanced vascularization and osseointegration via presenting triple-functional peptides.

作者信息

Liu Wenjie, Wang Qing, Liu Hao, He Suqin, Wang Hongxiang, Xu Chengwei, Jin Chaofan, Li Na, Li Lianxin

机构信息

Wenzhou Institute, University of Chinese Academy of Sciences, 325001, China.

Yongkang First People's Hospital of Wenzhou Medical University, Yongkang, Zhejiang, 321300, China.

出版信息

J Orthop Translat. 2025 Apr 22;52:150-166. doi: 10.1016/j.jot.2025.03.020. eCollection 2025 May.

Abstract

BACKGROUND

Titanium-based implants have demonstrated good mechanical properties and biocompatibility in clinical applications, however, their inherent low bioactivity and complex biological behaviors during the process of osseointegration have resulted in a high rate of long-term implant failure. Although the immobilization of highly bioactive peptides on the implant surface is an effective strategy to improve osseointegration, the existing mono- and bifunctional peptide-modified implant surfaces can hardly meet the needs of cell behavior regulation and tissue regeneration during the process of osseointegration, and there is an urgent need for the development of more efficient surface modification technologies.

METHODS

In the present study, a multifunctional peptide-modified implant material, MPN@K6, was successfully prepared by linking one end of a tripeptide system (cell adhesion peptide RGD, osteogenic growth peptide OGP, and pro-angiogenic peptide ang), which possesses a specific biological function, to hexameric lysine, and constructing the tripeptide system on the surface of metal-polyphenol coatings (MPNs) by means of non-covalent interactions between the lysine and the polyphenol, and then the MPN@K6 - RGD/OGP/ang was used as a peptide modification. RGD/OGP/ang.

RESULTS

The MPN@K6-RGD/OGP/Ang coating not only supported the early adhesion and migration, late osteogenesis and mineralization of BMSCs, but also promoted the adhesion, migration and vascularization of HUVECs. RT-qPCR results showed that the hybrid peptide up-regulated the expression of key factors in angiogenesis and osteogenesis. In vivo testing further confirmed these findings, with the functional peptide coating being 1.5 to 2 times more effective at inducing new bone formation at an early stage than the other two-peptide combinations, confirming the effectiveness and superiority of the tripeptide synergistic modification strategy.

CONCLUSIONS

The results showed that the MPN@K6 - RGD/OGP/ang-modified implant exhibited significant advantages at the cellular level compared to different combinations of bifunctional peptide-coated forms. It was able to promote early cell migration and adhesion more efficiently, significantly induced osteoblast differentiation and mineralization, and enhanced the level of local vascularization. In a rat bone defect animal model, the material demonstrated more excellent bone repair effects and achieved better bone healing results, confirming the effectiveness and superiority of the tripeptide synergistic modification strategy.

THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE

The trifunctional peptide coating (MPN@K6 - RGD/OGP/Ang) constructed in this paper has a mild preparation process, is biologically safe, facilitates large-scale production, has a positive effect on bone tissue repair, and has a great potential for clinical application in orthopedic and dental implants.

摘要

背景

钛基植入物在临床应用中已展现出良好的机械性能和生物相容性,然而,其固有的低生物活性以及骨整合过程中复杂的生物学行为导致长期植入失败率较高。尽管将具有高生物活性的肽固定在植入物表面是改善骨整合的有效策略,但现有的单功能和双功能肽修饰的植入物表面在骨整合过程中难以满足细胞行为调控和组织再生的需求,迫切需要开发更高效的表面修饰技术。

方法

在本研究中,通过将具有特定生物学功能的三肽系统(细胞黏附肽RGD、成骨生长肽OGP和促血管生成肽ang)的一端与六聚赖氨酸相连,并借助赖氨酸与多酚之间的非共价相互作用在金属-多酚涂层(MPNs)表面构建三肽系统,成功制备了一种多功能肽修饰的植入材料MPN@K6,然后将MPN@K6-RGD/OGP/ang用作肽修饰。RGD/OGP/ang。

结果

MPN@K6-RGD/OGP/Ang涂层不仅支持骨髓间充质干细胞的早期黏附与迁移、后期成骨和矿化,还促进了人脐静脉内皮细胞的黏附、迁移和血管生成。RT-qPCR结果表明,杂合肽上调了血管生成和成骨关键因子的表达。体内测试进一步证实了这些发现,功能肽涂层在早期诱导新骨形成方面比其他两种肽组合有效1.5至2倍,证实了三肽协同修饰策略的有效性和优越性。

结论

结果表明,与双功能肽涂层形式的不同组合相比,MPN@K6-RGD/OGP/ang修饰的植入物在细胞水平上具有显著优势。它能够更有效地促进早期细胞迁移和黏附,显著诱导成骨细胞分化和矿化,并提高局部血管化水平。在大鼠骨缺损动物模型中,该材料表现出更优异的骨修复效果,实现了更好的骨愈合结果,证实了三肽协同修饰策略的有效性和优越性。

本文的转化潜力

本文构建的三功能肽涂层(MPN@K6-RGD/OGP/Ang)制备过程温和,生物安全性好,便于大规模生产,对骨组织修复有积极作用,在骨科和牙科植入物的临床应用中具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b8/12047590/9115799363fa/ga1.jpg

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