Antimicrobial Nanofibres for Diabetic Chronic Wound Healing

Diabetic chronic wounds are distressful for the patient, and have a higher risk of infection and sepsis, as a result of defects in the host response and immunity (Peacock et al, 2011). As there is no specific treatment for sepsis and mortality rates are over 20% (Cohen et al, 2012), preventing infection in diabetic non-healing wounds is of major importance.

Antiseptics have been used since the 1960s to prevent infection, as they are effective against a wide range of different types of yeasts, fungi, moulds and bacteria and result in relatively low levels of antimicrobial resistance (Mulder et al, 2007; Landis, 2008). There are many different antiseptics currently used in healthcare (Landis, 2008). However, many have undesired side effects or have poor delivery systems available: silver leads to skin sensitization and has limited tissue penetration; chlorhexidine causes skin sensitization; iodine based antiseptics stain the skin and some delivery systems for iodine can reduce wound healing or lead to skin sensitization (Mulder et al, 2007; Landis, 2008).

Polyhexamethylene biguanide (PHMB), also known as polyaminopropyl biguanide and polyhexanide, is a polymeric biguanide compound commonly used as a broad-spectrum antiseptic (Mulder et al, 2007; Chindera et al, 2016). It has been recorded to work through microbial membrane disruption with minimal host cell damage (Chindera et al, 2016; Gilbert et al, 1990; Mafra et al, 2013; Kramer et al, 2004), and through selectively binding and condensing bacterial DNA within the nucleus, leaving host cells unaffected (Chindera et al, 2016). This also allows PHMB to be low risk for antimicrobial resistance, of which, none has been recorded despite extensive testing and usage since its first synthesis(Chindera et al, 2016). The superiority of PHMB in having a minimal adverse effect on host cells means that wound closures have been recorded to be faster when compared to other antimicrobial agents (Kramer et al, 2004), giving further benefits for would healing and preventing sepsis.

There have been many different methods attempted for the successful delivery of PHMB that are relevant to wound treatment. However, there have been mixed results with some failing to reflect the antimicrobial characteristics of the polymer (Siadat et al, 2018; Napavichayanun et al, 2016; Forstner et al, 2013, Eberlein et al, 2012). The aim of this PhD project is to electrospin PHMB with polyurethane to manufacture antimicrobial nanofibres that promote wound healing. As the use of nanotechnology increases the surface area available, it could allow for a more gradual release of PHMB. Therefore, it is hypothesised that electrospinning PHMB will allow for a more controlled delivery to the wound bed and lead to superior healing when compared to products already used in clinic. Other molecules and materials will also be investigated during the PhD to create a well-rounded diabetic chronic wound covering to use in clinic.