In Vivo Antibacterial Efficacy of Antimicrobial Peptides Modified Metallic Implants─Systematic Review and Meta-Analysis

Biomaterial-associated infection is difficult to detect and brings consequences that can lead to morbidity and mortality. Bacteria can adhere to the implant surface, grow, and form biofilms. Antimicrobial peptides (AMPs) can target and kill bacterial cells using a plethora of mechanisms of action such as rupturing the cell membrane by creating pores via depolarization with their cationic and amphipathic nature. AMPs can thus be coated onto metal implants to prevent microbial cell adhesion and growth. The aim of this systematic review was to determine the potential clinical applications of AMP-modified implants through in vivo induced infection models. Following a database search recently up to 22 January 2022 using PubMed, Web of Science and Cochrane databases, and abstract/title screening using the PRISMA framework, 24 studies remained, of which 18 were used in the random effects meta-analysis of standardized mean differences (SMD) to get effect sizes. Quality of studies was assessed using SYRCLE's risk of bias tool. The data from these 18 studies showed that AMPs carry antibacterial effects, and the meta-analysis confirmed the favorited antibacterial efficacy of AMP-coated groups over controls (SMD -1.74, 95%CI [-2.26, -1.26], p < 0.00001). Subgroup analysis showed that the differences in effect size are random, and high heterogeneity values suggested the same. HHC36 and vancomycin were the most common AMPs for surface modification and Staphylococcus aureus , the most tested bacterium in vivo. Covalent binding with polymer brush coating and physical layer-by-layer incorporation of AMPs were recognized as key methods of incorporation to achieve desired densities. The use of fusion peptides seemed admirable to incorporate additional benefits such as osteointegration and wound healing and possibly targeting more microbe strains. Further investigation into the incorporation methods, AMP activity against different bacterial strains, and the number of AMPs used for metal implant surface modification is needed to progress toward potential clinical application.