Adaptive cationic peptide bundles hydrogel for the repair of infected mandibular defects

Due to bacterial resistance and the limited self-healing capacity, the treatment of infected mandibular defects remains great challenges. Cationic peptide bundles can kill bacteria more efficiently than the linear ones. However, they are hard to release from hydrogels because of the nonflexible structures, thus limiting its application. Inspired by the calcium-alginate reversible domain, we constructed an adaptive peptide bundles-loaded hydrogel with Schiff bases. The alginate was first oxidized to increase aldehyde groups. Gelatin (amino group) and icariin (hydroxyl group) were employed to stabilize the network. Interestingly, the peptide bundles significantly enhanced the mechanical strength, and hardly released from the hydrogels, revealing the stable bond with the network in neutral conditions. During infections, the peptide bundles were adaptively released in response to the bacteria-induced changes in acidic environment. Results showed that the peptide bundles could penetrate the bacteria membrane and lead to the ATP breakage. After immersing hydrogels in acidic solutions, cells could grow more deeply compared to the non-treated group, which promoted proliferation and osteogenesis. In vivo studies showed that the adaptive peptide bundles-loaded hydrogel could eliminate infections, decrease the formation of neutrophil extracellular networks and accelerate the healing process, leading to enhanced bone formation. This study provides a novel and promising approach for the clinical management of infectious maxillofacial bone defects.