Abstract
Medical devices such as orthopedic and dental implants may get infected by bacteria, which results in treatment using antibiotics. Since antibiotic resistance is increasing in society there is a need of finding alternative strategies for infection control. One potential strategy is the use of antimicrobial peptides, AMPs. In this study, we investigated the antibiofilm effect of the AMP, RRP9W4N, using a local drug-delivery system based on mesoporous titania covered titanium implants. Biofilm formation was studied in vitro using a safranine biofilm assay and LIVE/DEAD staining. Moreover, we investigated what effect the AMP had on osseointegration of commercially available titanium implants in vivo, using a rabbit tibia model. The results showed a sustained release of AMP with equal or even better antibiofilm properties than the traditionally used antibiotic Cloxacillin. In addition, no negative effects on osseointegration in vivo was observed. These combined results demonstrate the potential of using mesoporous titania as an AMP delivery system and the potential use of the AMP RRP9W4N for infection control of osseointegrating implants.
Highlights
A majority of orthopedic implant-related infections are caused by the skin bacteria Staphylococcus epidermidis and Staphylococcus aureus.[1]
We investigated the antibacterial effect of the PRELP-derived antimicrobial peptide RRPRPRPRPWWWW-NH2 (RRP9W4N) when incorporated into mesoporous titania
The peptide was loaded in mesoporous titania, which was coated into titanium implants
Summary
A majority of orthopedic implant-related infections are caused by the skin bacteria Staphylococcus epidermidis and Staphylococcus aureus.[1]. Proteolytically stable antimicrobial peptides with low toxicity for human cells and high bactericidal effect, even against multi-resistant bacterial strains of S. aureus, Group A streptococci, Escherichia coli and P. aeruginosa, can be obtained.[5] Engineered AMPs have shown antibacterial properties against other bacteria like Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, Enterobacter cloacae and Escherichia coli.[6,7] In addition to engineering AMPs, their stability and function may be improved by the mode of delivery.[8]. RRP9W4N has shown to have good bacterial killing properties combined with low toxicity to bone forming cells, human osteosarcoma MG63 cells, and human mesenchymal stem cells in vitro.[18] The loading and release of peptide from mesoporous titania was investigated as was the antibacterial effect, using a S. epidermidis biofilm safranine assay together with LIVE/DEAD BacLight staining and confocal laser scanning microscopy. In the in vivo study, commercially available dental titanium implants were installed and followed at different healing times
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