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

Wei Zhou, Yang Liu, Xuan Nie, Chen Zhu (), Liming Xiong (), Jing Zhou () and Wei Huang ()
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Wei Zhou: University of Science and Technology of China
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

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-58444-8

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