Ephemeral biogels to control anti-biofilm agent delivery: From conception to the construction of an active dressing

Chronic wound colonization by bacterial biofilms is common and can cause various complications. An anti-biofilm strategy was developed around the co-entrapment of a commercially available antiseptic, PHMB (polyhexamethylene biguanide 4 mg mL(-1)), with EDTA (Ethylen diamine tetra acetic acid, 20 mM) in a gelatin gel. The two active compounds act synergistically against bacterial biofilms, but their efficiency is strongly reduced (16-fold) when entrapped inside the 5% gelatin gel, and they weaken the mechanical properties (50 fold) of the gel. Increasing the gelatin concentration to 7% allows for good mechanical properties but large diffusional constraints. An active ephemeral gel, a chemical gel with controlled hydrolysis, was conceived and developed. When the ephemeral gel was solubilized after 48 h, PHMB delivery increased, leading to good anti-biofilm activity. The various gels were examined over 24 and 48 h of contact with P. aeruginosa and S. aureus biofilms, two types of bacterial biofilms frequently encountered in chronic wounds. The ephemeral gel eradicated the dense biofilms ( > 6.10(7) CFU.cm(-2)) produced by either single or mixed strains; a similar efficiency was measured for biofilms from strains of both laboratory and clinical origin. The formulation was then adapted to develop a dressing prototype that is active against biofilms and fulfils the requirements of an efficient wound care system.