# Dual‐Anchored Clickable Peptide via SPAAC for Gelatinase‐Responsive Antibacterial and Osteogenic Functions on Titanium Implants

## TL;DR

This paper introduces a titanium implant with a dual-anchored peptide that fights infection while supporting bone growth, offering a solution to a major clinical challenge in orthopedic implants.

## Contribution

A novel dual-anchored peptide design that preserves osteogenic function while enabling antibacterial activity in response to infection.

## Key findings

- The Ti-Dual implant eliminated 99.37% of P. aeruginosa within 10 minutes and 99.99% within 120 minutes.
- The RGD motif remained anchored post-activation, ensuring continuous cell adhesion and tissue integration.
- In vivo, Ti-Dual suppressed inflammation, mitigated bone resorption, and enhanced osteogenesis in a rat model.

## Abstract

Antibacterial orthopedic implants that simultaneously promote osteointegration remain an unmet clinical challenge. Conventional enzyme‐responsive antibacterial surfaces often suffer from irreversible loss of osteogenic motifs upon activation, limiting their regenerative capacity post‐infection. Herein, we report a dual‐anchored peptide design engineered on titanium implants (Ti‐Dual) that addresses this limitation by retaining biofunctional motifs after pathogen‐triggered activation. The peptide construct integrates an antimicrobial sequence (HHC36) and a cell‐adhesive RGD motif connected via a gelatinase‐cleavable spacer (GPLGV). Terminal azide groups enable stable dual‐point grafting through SPAAC chemistry, overcoming the low grafting efficiency associated with mixed RGD grafting systems. Under physiological conditions, the constrained conformation suppresses antibacterial activity, favoring osteogenesis. Upon infection, bacterial gelatinase cleaves the linker, activating rapid and potent antibacterial effects—eliminating 99.37% of P. aeruginosa within 10 min, and 99.73% of S. aureus and 99.99% of P. aeruginosa within 120 min—while the RGD motif remains anchored, ensuring continuous cell adhesion and tissue integration. In vivo, Ti‐Dual effectively eradicated multidrug‐resistant P. aeruginosa, suppressed inflammatory responses, mitigated bone resorption, and enhanced osteogenesis in a rat femoral infection model. This design resolves the critical trade‐off between infection responsiveness and sustained pro‐regenerative function, offering a robust and adaptive strategy for infected bone defect repair.

To address the infection‐associated orthopedic implant failures, this study presents a gelatinase‐responsive antibacterial titanium implant (Ti‐Dual) featuring a dual‐anchored fusion peptide containing antibacterial (HHC36) and osteogenic (RGD) domains connected by a cleavable GPLGV linker. Under infection, bacterial gelatinase triggers antibacterial function while preserving RGD‐mediated bone‐repair activity. In vivo results demonstrate effective P. aeruginosa eradication, reduced inflammation, and enhanced bone regeneration.