Abstract

Aging population has been boosting the need for orthopedic implants. However,  biofilm has been a major obstacle for orthopedic implants due to its insensitivity to antibiotics and  tendency to drive antimicrobial resistance. Herein, an antibacterial polypeptide coating with  excellent in vivo adhesive capacity was prepared to prevent implants from forming biofilms and  inducing acquired antibiotic resistance. A peptide-based copolymer, poly[phenylalanine10-stat-lysine12]-block-3,4-dihydroxy-L-phenylalanine [Poly(Phe10-stat-Lys12)-DOPA] was modularly  designed, where poly(Phe10-stat-Lys12) is antibacterial polypeptide with high antibacterial activity,  and DOPA provides strong adhesion in both wet and dry microenvironments. Meanwhile,  compared to traditional “graft-onto” methods, this antibacterial coating can be facilely achieved  by immersing Titanium substrates into antibacterial polypeptide solution for 5 min at room  temperature. The poly(Phe10-stat-Lys12)-DOPA polymer showed good antibacterial activity with  minimum inhibitory concentrations against S. aureus and E. coli of 32 and 400 μg/mL,  respectively. Compared to obvious antimicrobial resistance of S. aureus after continuous treatment  with vancomycin, this antibacterial coating doesn’t drive antimicrobial resistance upon long-term  utilization. Transcriptome sequencing and qPCR tests further confirmed that the antibacterial  coating was able to inhibit the expression of multiple peptide resistance factor (mprF) and  lipoteichoic acid modification D-alanylation genes (dltB and dltC) that can increase the net  positive charge of bacterial cell wall to induce the resistance to cationic antimicrobial peptides. In  vivo experiments confirmed that this poly(Phe10-stat-Lys12)-DOPA coating can both effectively  prevent biofilm formation through surface contact sterilization and avoiding local and systemic  infections. Overall, we proposed a facile method for preparing antibacterial orthopedic implants  with longer indwelling time and without inducing antimicrobial resistance by coating a  polypeptide-based polymer on the implants.

文章链接：Biomaterials 2023, 293, 121957.