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Peptide-based inflammation-responsive implant coating sequentially regulates bone regeneration to enhance interfacial osseointegration

Author

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  • Wei Zhou

    (University of Science and Technology of China
    Huazhong University of Science and Technology)

  • Yang Liu

    (University of Science and Technology of China)

  • Xuan Nie

    (University of Science and Technology of China)

  • Chen Zhu

    (University of Science and Technology of China)

  • Liming Xiong

    (Huazhong University of Science and Technology)

  • Jing Zhou

    (University of Science and Technology of China)

  • Wei Huang

    (University of Science and Technology of China)

Abstract

Aseptic loosening is the primary cause of bone prosthesis failure, commonly attributed to inadequate osseointegration due to coatings misaligned with bone regeneration. Here, we modify the titanium surface with a mussel-inspired peptide to form a 3,4-dihydroxyphenylalanine (DOPA)-rich coating, then graft N3-K15-PVGLIG-K23 (P1) and N3-Y5-PVGLIG-K23 (P2), which are composed of anti-inflammatory (K23), angiogenic (K15), osteogenic (Y5), and inflammation-responsive (PVGLIG) sequences, onto the surface via click chemistry, forming the DOPA-P1@P2 coating. DOPA-P1@P2 promotes bone regeneration through sequential regulation. In the initial stage, the outermost K23 induces M2 macrophage polarization, establishing a pro-regenerative immune microenvironment. Subsequently, K15 and Y5, exposed by the release of K23, enhance angiogenesis and osteogenesis. In the final stage, DOPA-P1@P2 outperforms the TiO₂ control, showing a 161% increase in maximal push-out force, a 207% increase in bone volume fraction, and a 1409% increase in bone-to-implant contact. These findings show that DOPA-P1@P2 efficiently enhances interfacial osseointegration by sequentially regulating bone regeneration, providing viable insights into coating design.

Suggested Citation

  • Wei Zhou & Yang Liu & Xuan Nie & Chen Zhu & Liming Xiong & Jing Zhou & Wei Huang, 2025. "Peptide-based inflammation-responsive implant coating sequentially regulates bone regeneration to enhance interfacial osseointegration," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58444-8
    DOI: 10.1038/s41467-025-58444-8
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    References listed on IDEAS

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    1. Tao Wang & Jiaxiang Bai & Min Lu & Chenglong Huang & Dechun Geng & Gang Chen & Lei Wang & Jin Qi & Wenguo Cui & Lianfu Deng, 2022. "Engineering immunomodulatory and osteoinductive implant surfaces via mussel adhesion-mediated ion coordination and molecular clicking," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Wenjing Jin & Xianfeng Lin & Haihua Pan & Chenchen Zhao & Pengcheng Qiu & Ruibo Zhao & Zihe Hu & Yanyan Zhou & Haiyan Wu & Xiao Chen & Hongwei Ouyang & Zhijian Xie & Ruikang Tang, 2021. "Engineered osteoclasts as living treatment materials for heterotopic ossification therapy," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
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