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

Biomaterial-associated infection is difficult to detectand 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 cellsusing a plethora of mechanisms of action such as rupturing the cellmembrane by creating pores via depolarization with their cationicand amphipathic nature. AMPs can thus be coated onto metalimplants to prevent microbial cell adhesion and growth. The aim ofthis systematic review was to determine the potential clinicalapplications of AMP-modified implants through in vivo inducedinfection models. Following a database search recently up to 22January 2022 using PubMed, Web of Science and Cochranedatabases, 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 geteffect sizes. Quality of studies was assessed using SYRCLE's risk of bias tool. The data from these 18 studies showed that AMPs carryantibacterial 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 highheterogeneity values suggested the same. HHC36 and vancomycin were the most common AMPs for surface modification andStaphylococcus aureus, the most tested bacterium in vivo. Covalent binding with polymer brush coating and physical layer-by-layerincorporation of AMPs were recognized as key methods of incorporation to achieve desired densities. The use of fusion peptidesseemed admirable to incorporate additional benefits such as osteointegration and wound healing and possibly targeting moremicrobe strains. Further investigation into the incorporation methods, AMP activity against different bacterial strains, and thenumber of AMPs used for metal implant surface modification is needed to progress toward potential clinical application.