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


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

Highlights

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

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

  • This hydrogel combats micro organism by sustained launch and multi-target motion towards membranes, DNA, and biofilms.

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

  • Hydrogel-coated implants successfully inhibit infections and help osseointegration and mineralization in vivo.

Summary

Implant-associated infections (IAIs) stay a significant reason for implant failure, necessitating the event of efficient anti-infection coatings for orthopedic implants. Right here, we found a penetratin derived antimicrobial peptide (AMP) that spontaneously self-assembles right into a mechanically inflexible hydrogel with elongated fibrils by forming a triple helix construction. Molecular simulations revealed that intermolecular cation-π and π-π interactions, together with interfibrillar hydrogen bonds and electrostatic salt bridges, are important for hydrogelation. The ensuing hydrogel exhibited excessive biocompatibility, sustained AMP launch, and potent broad-spectrum antimicrobial exercise. Titanium sheets coated with resultant hydrogel successfully inhibited Staphylococcus aureus (S. aureus) progress for 7 days in vitro. Moreover, the hydrogel demonstrated superior anti-infection efficacy as an implant coating, selling osseointegration and mineralization in a rat mannequin of osteomyelitis induced by implant an 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 applied sciences.

Graphical Summary

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

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This work reported that P2 may self-assemble right into a hydrogel (gel 2) with a triple-helix construction, providing sustained broad-spectrum antimicrobial exercise and biocompatibility. In rat fashions, gel 2-coated titanium implants efficiently prevented S. aureus an infection and enhanced osseointegration. These outcomes spotlight gel 2 as a novel, antibiotic-free strategy for bettering outcomes in orthopedic surgical procedures.

Part snippets

Outcomes and dialogue

Penetratin is acknowledged for its average antimicrobial exercise. To reinforce its efficiency, 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 identified to advertise membrane interplay and injury [28], [29] (Desk 1, Fig. S14). As proven in Desk 1 and Fig. S5, these mutations considerably enhanced the antimicrobial exercise of penetratin towards 

Conclusion

On this examine, we engineered penetratin peptides by substituting non-conserved websites with hydrophobic amino acids, yielding candidates with enhanced antimicrobial properties. Amongst these, P2 uniquely self-assembled right into a hydrogel that includes a definite triple-helix construction. This hydrogel demonstrated broad-spectrum antimicrobial exercise, favorable biocompatibility, and a exceptional prolongation of efficacy, exceeding 48 instances that of its answer type. In comparison with typical β-sheet-based

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The Supporting Data is obtainable freed from cost

Authors

J.S. and L.W conceived the unique concepts and guided the mission. T.L., Q.Y., Y.C; L.W carried out the experiments. T.L. and Y.C analyzed all knowledge within 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. affords amenities and tools together with micro-CT and X-ray irradiator. All authors learn and accepted of the ultimate manuscript.

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

CRediT authorship contribution assertion

Wenbin Liu: Writing – evaluate & enhancing, Conceptualization. HongKun Hu: Writing – evaluate & enhancing. Binwen Yuan: Writing – evaluate & enhancing. Weijun Tang: Sources. Dan Yuan: Funding acquisition. Tingting Li: Writing – authentic draft, Validation, Mission administration, Funding acquisition, Information curation. Yu Chen: Writing – authentic draft, Information curation. Qipeng Yan: Writing – authentic draft, Information curation. Junfeng Shi: Writing – evaluate & enhancing, Funding acquisition, Conceptualization.

Declaration of Competing Curiosity

The authors declare the next monetary pursuits/private relationships which can be thought of as potential competing pursuits: Junfeng Shi experiences monetary help was supplied by Nationwide Youth Expertise Assist Program. Dan Yuan experiences monetary help was supplied by the Nationwide Pure Science Basis of China. Tingting Li experiences monetary help was supplied by Pure Science Basis of Hunan province. Dan Yuan experiences monetary help was supplied by Pure Science

Acknowledgment

We recognize the technical help supplied by the Analytical Instrumentation Middle of Hunan College for Help in Confocal Microscopy. This work was partially supported by the Nationwide Pure Science Basis of China (32401127 to D.Y, 22505072 to T.L), Nationwide Youth Expertise Assist Program (202309460011), Pure Science Basis of Hunan province (2024JJ5072 to D.Y., 2025JJ80084 to T.L), The Key Mission of Hunan Provincial Training Division (22A0020 to D.Y.), Pure Science

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