Developmental Strategies to Address Prosthetic Infection of Biomaterials

Considering the high prevalence rates and the lack of a current gold-standard treatment, peri-implant infection is rapidly becoming an – if not the most – important clinical challenge for indwelling medical devices. As an alternative to current perioperative antibiotic prophylactic treatments, a plethora of biomaterial/bioengineering based antimicrobial strategies are emerging to restrict or ideally to eliminate microbial adhesion and biofilm formation on the implant surfaces. Yet, the development of such approaches faces specific challenges, such as biocompatibility concerns, reduced antimicrobial effectiveness, long-term stability issues and antibiotic resistance development, which limit translation into the clinical setting. In this lecture, I will present two generic approaches, which demonstrate labscale success to induce bactericidal or bacteriostatic effects, in vitro. The biomaterials-based approaches will include the gold nanoparticles and HA-based antibacterial composites. The bioengineering approach will be discussed in reference to the intermittent delivery of electric or magnetic pulses to the bacterial growth medium, <i>in vitro</i>.<br/>The first part of the presentation will dwell on the bacteriotoxic effects of the ultrasmall GNPs with median sizes of 0.8 nm and 1.4 nm and stabilized by monosulphonated triphenylphosphine ligands. A near 5 log reduction in viable staphylococcal strains (<i>S.aureus</i> and <i>S.epidermidis</i>) was observed in the first 5 h of 0.8 nm and 1.4 nm GNP treatment. Apart from exhibiting bactericidal effect in planktonic cultures accompanied by membrane blebbing and cell wall thinning, a 2x MIC dosage of the ultrasmall GNPs caused around 80-90% reduction in the viability of staphylococcal biofilms, with marked biofilm destruction. The toxicity dosages of such GNPs provide a therapeutic dosage window for the utilization of ultrasmall GNPs as a treatment option against prosthetic infection.<br/>In the second part, three main antimicrobial strategies will be discussed – i) exposure of bacteria cultured on HA or HA-Fe₃O₄ composites, to moderate intensity static magnetic fields (SMF) of 100 mT; ii) exposure of pathogenic strains to high strength pulse magnetic field (PMF) of 1 – 4 Tesla and iii) electric field stimulation (1-2.5 V/cm) of pathogenic strains, when grown on conductive carbon or HA-ZnO composites. In all the instances, the possible mechanisms, including the synergistic effects of biomaterial properties with external stimulation parameters, for the observed bactericidal effect via the generation of reactive oxygen species and membrane damage will be discussed.<br/>Towards the end, it will be emphasized as how the integration of computational tools and experimental databases using artificial intelligence (AI) based approaches would spur the development of next generation technologies for accelerated discovery of antimicrobial strategies.