Abstract
Prevention of orthopedic implant-related infections is a major medical challenge, particularly due to the involvement of biofilm-encased and multidrug-resistant bacteria. Current therapies, based on antibiotic administration, have proven to be insufficient, and infection prevalence may rise due to the dissemination of antibiotic resistance. Antimicrobial peptides (AMPs) have attracted attention as promising substitutes of conventional antibiotics, owing to their broad-spectrum of activity, high efficacy at very low concentrations, and, importantly, low propensity for inducing resistance. The aim of this review is to offer an updated perspective of the development of AMPs-based preventive strategies for orthopedic and dental implant-related infections. In this regard, two major research strategies are herein addressed, namely (i) AMP-releasing systems from titanium-modified surfaces and from bone cements or beads; and (ii) AMP immobilization strategies used to graft AMPs onto titanium or other model surfaces with potential translation as coatings. In overview, releasing strategies have evolved to guarantee higher loadings, prolonged and targeted delivery periods upon infection. In addition, avant-garde self-assembling strategies or polymer brushes allowed higher immobilized peptide surface densities, overcoming bioavailability issues. Future research efforts should focus on the regulatory demands for pre-clinical and clinical validation towards clinical translation.
Highlights
As life expectancy grows worldwide, the need to repair or replace fragile/fractured bone and joints, through orthopedic surgery, increases [1]
The present review focuses on the potential of Antimicrobial peptides (AMPs)-based solutions to address orthopedic implant-related infections (Figure 1)
There are several parameters to be considered in performing a successful immobilization of active AMPs, such as the maintenance of the AMP antimicrobial structural features after immobilization [43], which is influenced by the spacer applied, as well as by the orientation and surface density of the immobilized peptide [92]
Summary
As life expectancy grows worldwide, the need to repair or replace fragile/fractured bone and joints, through orthopedic surgery, increases [1]. These promising results prompted the same research group to evaluate the Bonesource CaP cement loaded with hLF1-11 (50 mg/g) in a S. aureus rabbit osteomyelitis prevention model (femur osteomyelitis) [53] This was the first study describing the in vivo efficacy of a locally released AMP in the prevention of osteomyelitis. One limitation of this study is that the extent of penetration of AMPs and antibiotics into the surrounding bone tissue, as well as their release kinetics from the bone cement to the tissue, were not directly assessed Later, four of these halictine-2 series analogues were used by Volejníková et al for comparison with vancomycin in PMMA beads [29]. Different osteomyelitis models to assess in vivo performance of titanium implants have been recently reviewed [73,74]
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