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Introduction: Diabetes mellitus is a metabolic disorder leading to multiple health conditions including diabetic foot ulcers (DFUs), which often become infected. Current therapies are ineffective and contribute to antimicrobial resistance (AMR). Therefore, new non-antibiotic treatments are required. Cold Atmospheric Plasma (CAP), an ionised gas, has the potential to resolve infection by delivering reactive species (RS) such as hydrogen peroxide (H2O2) deep into the wound. CAP can also be used to deliver antimicrobial drugs from a hydrogel dressing also known as plasma-activated hydrogel therapy (PAHT). Aim: To investigate the potential of a PAHT for the treatment of infected DFUs. Methods: A systematic review compared two bacterial detection techniques – 16S rRNA gene sequencing and conventional culture. The physical (electrical and optical) and chemical (RS delivery) characteristics of CAP jet were studied. Povidone-iodine (PVP-I) solution and PVP-I from a hydrogel (i.e. PVP-I–PAHT) exposed to CAP were assessed using UV-visible spectroscopy and agarose-starch assays. The antibacterial efficiency of PVP-I–PAHT was assessed using checkerboard synergy assay, Kirby-Bauer Assay, and a wound biofilm model. Results: The review demonstrated the Staphylococcal spp. and Pseudomonas spp. predominance in DFUs. A low-power CAP jet, which can deliver up to 1.91 mM of H2O2 in solution was established. A potential formation of hypoiodous acid (HOI) was shown upon the interaction of PVP-I with CAPproduced H2O2. Complete eradication of an immature biofilm and a log 2 reduction against 1 hour incubated mature biofilms were observed with PVP-I–PAHT. Conclusion: This is the first study to investigate the properties of plasma-activated PVP-I and the anti-microbial activity of PVP-I–PAHT against the bacteria specific to DFUs. It also highlights the role of H2O2 and HOI in CAP–PVP-I treatment of DFUs. An existing antimicrobial (PVP-I) was repurposed with non-antibiotic CAP technology whic

Introduction: Diabetes mellitus is a metabolic disorder leading to multiple health conditions including diabetic foot ulcers (DFUs), which often become infected. Current therapies are ineffective and contribute to antimicrobial resistance (AMR). Therefore, new non-antibiotic treatments are required. Cold Atmospheric Plasma (CAP), an ionised gas, has the potential to resolve infection by delivering reactive species (RS) such as hydrogen peroxide (H2O2) deep into the wound. CAP can also be used to deliver antimicrobial drugs from a hydrogel dressing also known as plasma-activated hydrogel therapy (PAHT). Aim: To investigate the potential of a PAHT for the treatment of infected DFUs. Methods: A systematic review compared two bacterial detection techniques – 16S rRNA gene sequencing and conventional culture. The physical (electrical and optical) and chemical (RS delivery) characteristics of CAP jet were studied. Povidone-iodine (PVP-I) solution and PVP-I from a hydrogel (i.e. PVP-I–PAHT) exposed to CAP were assessed using UV-visible spectroscopy and agarose-starch assays. The antibacterial efficiency of PVP-I–PAHT was assessed using checkerboard synergy assay, Kirby-Bauer Assay, and a wound biofilm model. Results: The review demonstrated the Staphylococcal spp. and Pseudomonas spp. predominance in DFUs. A low-power CAP jet, which can deliver up to 1.91 mM of H2O2 in solution was established. A potential formation of hypoiodous acid (HOI) was shown upon the interaction of PVP-I with CAPproduced H2O2. Complete eradication of an immature biofilm and a log 2 reduction against 1 hour incubated mature biofilms were observed with PVP-I–PAHT. Conclusion: This is the first study to investigate the properties of plasma-activated PVP-I and the anti-microbial activity of PVP-I–PAHT against the bacteria specific to DFUs. It also highlights the role of H2O2 and HOI in CAP–PVP-I treatment of DFUs. An existing antimicrobial (PVP-I) was repurposed with non-antibiotic CAP technology whic