ICF: Novel Antimicrobial Peptides for Local Wound Sepsis Control

Wounds are breeding grounds for bacteria and hence infection is the major contributor to morbidity in patients, causing delayed healing, loss of skin grafts and sepsis. Delayed wound healing causes significant functional and psychological morbidity for patients, loss of limbs (in diabetes) or even loss of life (in burns). Wound dressings represent an important approach for wound care and management, but there is little evidence to support the routine use of the current antimicrobial dressings for complex wounds. Most antimicrobial dressings do not show clear wound healing benefits. This could be due to limitations such as local cytotoxicity, lack of penetrance and variable antimicrobial efficacy. Conventional antibiotics should be avoided for repeated or prolonged uses in wound care, because of the emergence of pathogens resistant to these commonly used antimicrobials. This highlights the urgent need for novel approaches.
We are developing novel patented antimicrobial peptide (AMP) releasing hydrofibre dressings with a broad-spectrum activity against bacteria, to stem wound infection and improve wound healing. Our AMP has been developed through rational design, selected from many dozens of candidates, and tested against a range of microbes. The dressing will have a broad-spectrum of activity against wound isolated pathogens, feature high potency against resistant microbes, have fast dynamic kill, and high penetrance through resistant biofilms. Our AMP is easy to synthesize, highly stable and non-toxic. Our prototype wound dressing is designed to recognise the healthcare needs from clinicians and patients, including ease of application and removal, exudate management and affordability. The technology would represent a valuable addition to current wound care.

Wounds are a major healthcare and economic burden, costing the NHS around £8.3 billion a year [1]. Wounds readily become infected, causing delayed healing, loss of skin grafts and sepsis. Delayed wound healing and sepsis may even lead to significant functional and psychological morbidity for patients, loss of limbs (in diabetes) or even loss of life (in burns) [2].
Dressings play an important role in wound management, but clinical guidance and Cochrane reviews show limited evidence to support the routine use of the current antimicrobial dressings for complex wounds [3]. Many antimicrobial dressings suffer from local cytotoxicity, and lack of penetrance and efficacy, whilst the use of systemic antibiotics should be minimised to limit the rise in resistant pathogens. Silver dressings, the dominant type of antimicrobial dressing products, have shown mixed clinical outcomes [4]; recent studies indicate silver ions and nanoparticles are cytotoxic [5], can cause localised tissue staining, are expensive and non-renewable, therefore imposing an environmental burden. Negative pressure wound therapy, used in conjunction with debridement, is difficult to apply, and requires specialist training and expensive equipment. This situation highlights the urgent need for novel approaches.
Antimicrobial peptides (AMPs) are an emergent technology platform which are cost-effective to manufacture and have potential to control wound infection [6]. Despite AMPs demonstrating high efficacy against several pathogenic microorganisms [6,7], a gap remains in demonstrating their potency against wound pathogens, especially antibiotic resistant strains. This project will 1) develop a hydrofibre based dressing loaded with AMP and perform confirmatory spectrum-of-efficacy studies using established wound models; and 2) compile a robust regulatory package including in vivo toxicology, biodistribution, safety and efficacy to further develop our intellectual property and commercial engagement.