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    A self-delivering antimicrobial peptide hydrogel for treatment of staphylococcal infections in orthopedic implants

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    A self-delivering antimicrobial peptide hydrogel for treatment of staphylococcal infections in orthopedic implants


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    https://doi.org/10.1016/j.nantod.2025.102963Get rights and content

    Highlights

    • •

      Biofilms and antibiotic resistance are key drivers of orthopedic implant infections and failure.

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      A novel antibiotic-free, penetratin-derived peptide hydrogel with a triple-helix structure was developed for implant coating.

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      This hydrogel combats bacteria by sustained release and multi-target action against membranes, DNA, and biofilms.

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      Multi-target action, aided by supramolecular peptide insertion, prevents bacterial resistance.

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      Hydrogel-coated implants effectively inhibit infections and support osseointegration and mineralization in vivo.

    Abstract

    Implant-associated infections (IAIs) remain a major cause of implant failure, necessitating the development of effective anti-infection coatings for orthopedic implants. Here, we discovered a penetratin derived antimicrobial peptide (AMP) that spontaneously self-assembles into a mechanically rigid hydrogel with elongated fibrils by forming a triple helix structure. Molecular simulations revealed that intermolecular cation-π and π-π interactions, along with interfibrillar hydrogen bonds and electrostatic salt bridges, are essential for hydrogelation. The resulting hydrogel exhibited high biocompatibility, sustained AMP release, and potent broad-spectrum antimicrobial activity. Titanium sheets coated with resultant hydrogel effectively inhibited Staphylococcus aureus (S. aureus) growth for 7 days in vitro. Furthermore, the hydrogel demonstrated superior anti-infection efficacy as an implant coating, promoting osseointegration and mineralization in a rat model of osteomyelitis induced by implant infection. This work highlights the potential of self-delivery antibacterial peptide hydrogel as a promising platform for prevention of implant infections and advancing orthopedic implant technologies.

    Graphical Abstract

    A self-delivering antimicrobial peptide hydrogel for treatment of staphylococcal infections in orthopedic implants

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    This work reported that P2 could self-assemble into a hydrogel (gel 2) with a triple-helix structure, offering sustained broad-spectrum antimicrobial activity and biocompatibility. In rat models, gel 2-coated titanium implants successfully prevented S. aureus infection and enhanced osseointegration. These results highlight gel 2 as a novel, antibiotic-free approach for improving outcomes in orthopedic surgeries.

    Section snippets

    Results and discussion

    Penetratin is recognized for its moderate antimicrobial activity. To enhance its potency, we strategically mutated its non-conserved amino acids (Asparagine, Asn9 and Methionine, Met12) with hydrophobic amino acids (e.g., isoleucine, Ile, and Tryptophan, Trp), as these hydrophobic residues are known to promote membrane interaction and damage [28], [29] (Table 1, Fig. S1–4). As shown in Table 1 and Fig. S5, these mutations substantially enhanced the antimicrobial activity of penetratin against 

    Conclusion

    In this study, we engineered penetratin peptides by substituting non-conserved sites with hydrophobic amino acids, yielding candidates with enhanced antimicrobial properties. Among these, P2 uniquely self-assembled into a hydrogel featuring a distinct triple-helix structure. This hydrogel demonstrated broad-spectrum antimicrobial activity, favorable biocompatibility, and a remarkable prolongation of efficacy, exceeding 48 times that of its solution form. Compared to typical β-sheet-based

    Associated content

    The Supporting Information is available free of charge

    Authors

    J.S. and L.W conceived the original ideas and guided the project. T.L., Q.Y., Y.C; L.W performed the experiments. T.L. and Y.C analyzed all data in the manuscript. J.S., T.L. and Q.Y wrote the manuscript. L.W.; D.Y, H.H. and B.Y edit the manuscript; W.T. offers facilities and equipment including micro-CT and X-ray irradiator. All authors read and approved of the final manuscript.

    T.L, Q.Y and Y.C contributed equally to this work.

    CRediT authorship contribution statement

    Wenbin Liu: Writing – review & editing, Conceptualization. HongKun Hu: Writing – review & editing. Binwen Yuan: Writing – review & editing. Weijun Tang: Resources. Dan Yuan: Funding acquisition. Tingting Li: Writing – original draft, Validation, Project administration, Funding acquisition, Data curation. Yu Chen: Writing – original draft, Data curation. Qipeng Yan: Writing – original draft, Data curation. Junfeng Shi: Writing – review & editing, Funding acquisition, Conceptualization.

    Declaration of Competing Interest

    The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Junfeng Shi reports financial support was provided by National Youth Talent Support Program. Dan Yuan reports financial support was provided by the National Natural Science Foundation of China. Tingting Li reports financial support was provided by Natural Science Foundation of Hunan province. Dan Yuan reports financial support was provided by Natural Science

    Acknowledgment

    We appreciate the technical support provided by the Analytical Instrumentation Center of Hunan University for Assistance in Confocal Microscopy. This work was partially supported by the National Natural Science Foundation of China (32401127 to D.Y, 22505072 to T.L), National Youth Talent Support Program (202309460011), Natural Science Foundation of Hunan province (2024JJ5072 to D.Y., 2025JJ80084 to T.L), The Key Project of Hunan Provincial Education Department (22A0020 to D.Y.), Natural Science

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    © 2025 Published by Elsevier Ltd.



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