Antimicrobial Peptides in the Battle against Orthopedic Implant-Related Infections: A Review

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.

Microbial resistance to nanotechnologies: An important but understudied consideration using antimicrobial nanotechnologies in orthopaedic implants

“…As an alternative approach, some AMPs can be grafted onto nanoparticles to exert antimicrobial functionality. Different material compositions and strategies to enable AMP-conjugated nano antimicrobials can be found in other review papers [ 171 , 172 ]. Despite enhanced stability and antibacterial performance by surface decoration relative to encapsulation by nanocarriers [ 173 ], the potent cytotoxicity of AMPs remains a significant risk factor yet to be resolved, which might lead to antimicrobial resistance.…”

“… Strength Weakness Opportunity Threat Ref Drug delivery systems Able to kill bacteria before attachment onto implant surface Unable to provide long term protection due to premature depletion of drugs Design of ‘smart’ delivery systems with release via various cues (temperature or pH) can vastly improve efficiency of strategy Premature depletion of drugs, causing emergence of antibiotic resistant strains [ 136 , 297 ] Co-delivery of a cocktail of various antimicrobial molecules can serve multiple therapeutic functions. Antimicrobial n anoparticles Intrinsic antimicrobial properties against antibiotic resistant bacteria strains Innate toxicity to host cells after long term exposure Immunomodulatory properties are largely unexplored and potentially can be harnessed with well controlled delivery Optimization is needed to prevent prolonged inflammation [ 171 ] Non-selective bactericidal property can potentially hinder development of antimicrobial resistance Development of resistance is not impossible Can be synergized with other strategies to improve antimicrobial effect Toxicity to humans cannot be fully replicated in animal models Anti-biofouling m aterials Inhibits bacterial attachment Eukaryotic cell attachment may be compromised Improvements in manufacturing...…”

Polymer Conjugates of Antimicrobial Peptides (AMPs) with d-Amino Acids (d-aa): State of the Art and Future Opportunities

“…To this end, a vivid research area concerns the development of macromolecules that are capable of avoiding the formation of biofilms [159], which are particularly challenging to eradicate [160]. Current antibiotic therapies are simply insufficient to address the insurgence of local infections in their immediate surroundings, especially in the long-term [161]. In addition to orthopaedics, dental healthcare [162], cardiac [163] and urological applications [164] are highly sought after.…”

Mini Review Therapeutic Strategies Targeting for Biofilm and Bone Infections

“…AMPs are part of the innate immune system and exhibit broad-spectrum antimicrobial activity against ESKAPE (referring to Enterococcus faecium , S. aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter sp.) ( Costa et al, 2021 ).…”