Bioinspired Multifunctional Peptides With Synergetic Anti-Infection, Immunomodulation And Osteogenesis

Infectious bone regeneration poses a substantial clinical challenge due to uncontrolled infection, excessive inflammation, and weakened regenerative potential. This study aims to design a novel peptide with synergetic antimicrobial, immunomodulatory and osteoinductive effects, and to provide a facile but effective strategy for intelligent integration of bioactivities. A novel peptide design concept called sequence transformation was proposed, on the basis of which, a panel of multifunctional peptides were synthesized utilizing the structure similarity of the lactoferrin and the osteogenic growth peptide. Then, the physiochemical properties of these peptides were investigated and three promising candidates, WL14, GL14 and GK16, were selected. Their inhibitory effects on planktonic pathogens, pathogenic biofilms and virulence factors were evaluated. Their osteoinductive performances on bone marrow mesenchymal stem cells (BMSCs) and immunomodulatory performances on macrophages were assessed as well. Specifically, a coculture system of macrophages and BMSCs were established and the osteogenic abilities of peptides to BMSCs by modulating immune responses of macrophages were studied. WL14, GL14 and GK16 presented ideal α-helical structures and excellent biocompatibilities. They could kill planktonic pathogens, eradicate biofilms and inhibit microbial virulence at 32 µg/mL. Additionally, at the same concentration, these three peptides could directly prompt the osteogenic differentiation of BMSCs, mitigate inflammatory responses of macrophages and facilitate their M2 polarization. In the inflammation-attenuated microenvironment engendered by peptides, the osteogenic performances of BMSCs were profoundly elevated. This study proposed a pioneering concept for the design of multifunctional peptides and provided a valuable insight into infected tissue repair.