Antimicrobial and enzyme-responsive multi-peptide surfaces for bone-anchored devices

Functionalization of dental and orthopedic implants with multiple bioactivities is desirable to obtain surfaces with improved biological performance and reduced infection rates. While many approaches have been explored to date, nearly all functionalized surfaces are static, i.e., non-responsive to biological cues. However, tissue remodeling necessary for implant integration features an ever-changing milieu of cells that demands a responsive biomaterial surface for temporal synchronization of interactions between biomaterial and tissue. Here, we successfully synthesized a multi-functional, dynamic coating on titanium by co-immobilizing GL13K antimicrobial peptide and an MMP-9 – a matrix metalloproteinase secreted by bone-remodeling osteoclasts – responsive peptide. Our co-immobilized peptide surface showed potent anti-biofilm activity, enabled effective osteoblast and fibroblast proliferation, and demonstrated stability against a mechanical challenge. Finally, we showed peptide release was triggered for up to seven days when the multi-peptide coatings were cultured with MMP-9-secreting osteoclasts. Our MMP-9 cleavable peptide can be conjugated with osteogenic or immunomodulatory motifs for enhanced bone formation in future work. Overall, we envisage our multifunctional, dynamic surface to reduce infection rates of percutaneous bone-anchored devices via strong anti-microbial activity and enhanced tissue regeneration via temporal synchronization between biomaterial cues and tissue responses.