ANTIBACTERIAL NANOPARTICLE INTEGRATED SCAFFOLDS FOR THE MANAGEMENT OF INFECTED WOUNDS:MATERIALS, MECHANISMS AND CLINICAL PERSPECTIVES

Abstract

Infected wounds are one of the most difficult and neglected problems in clinical medicine. Bacteria colonise a wound and form biofilm communities which are 100-1000 times more tolerant to antibiotics than their planktonic counterparts. Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii are globally distributed multidrug-resistant organisms. is a real concern. has reduced the effectiveness of traditional management of wound infections. An estimated 4.95 million deaths in 2019 were attributable to or associated with bacterial AMR (the 2022 analysis of global AMR) alone, placing this squarely in the realm of public health emergencies, not future concerns. That’s something this dissertation investigates using nanoparticle integrated scaffolds. Three types of nanoparticles (silver, zinc oxide and copper oxide) are reviewed in detail with evaluation of their synthesis methodology, physicochemical properties and antibacterial mechanisms. These materials kill bacteria simultaneously by disrupting membranes , producing reactive oxygen species , metal ion toxicity and direct penetration of biofilms . This is a multi-target approach which makes development of resistance much more difficult than with any single antibiotic. Embedding in hydrogel, electrospun nanofibre, three-dimensionally printed and bioceramic scaffold platforms overcome the problems of localisation, release kinetics and cytotoxicity that limit the use of free nanoparticles for open wounds. The preclinical evidence is always promising but there is little evidence from RCTs. The three major hurdles to clinical translation include manufacturing scalability, the small therapeutic window between bactericidal and cytotoxic concentrations and an unclear regulatory pathway. These are not insurmountable challenges, but they are problems that arise in the field that have not been sufficiently solved.