Designing Biodegradable PHA-Based 3D Scaffolds with Antibiofilm Properties for Wound Dressings: Optimization of the Microstructure/Nanostructure.

One major factor inhibiting natural wound-healing processes is infection through bacterial biofilms, particularly in the case of chronic wounds. In this study, the micro/nanostructure of a wound dressing was optimized in order to obtain a more efficient antibiofilm protein-release profile for biofilm inhibition and/or detachment. A 3D substrate was developed with asymmetric polyhydroxyalkanoate (PHA) membranes to entrap Dispersin B (DB), the antibiofilm protein. The membranes were prepared using wet-induced phase separation (WIPS). By modulating the concentration and the molecular weight of the porogen polymer, polyvinylpyrrolidone (PVP), asymmetric membranes with controlled porosity were obtained. PVP was added at 10, 30, and 50% w/w, relative to the total polymer concentration. The physical and kinetic properties of the quaternary nonsolvent/solvent/PHA/PVP systems were studied and correlated with the membrane structures obtained. The results show that at high molecular weight ( M _w = 360 kDa) and high PVP content (above 30%), pore size decreased and the membrane became extremely brittle with serious loss of physical integrity. This brittle effect was not observed for low molecular weight PVP ( M _w = 40 kDa) at comparable contents. Whatever the molecular weight, porogen content up to 30% increased membrane surface porosity and consequently protein uptake. Above 30% porogen content, the pore size and the physical integrity/mechanical robustness both decreased. The PHA membranes were loaded with DB and their antibiofilm activity was evaluated against Staphylococcus epidermidis biofilms. When the bacterial biofilms were exposed to the DB-loaded PHA membrane, up to 33% of the S. epidermidis biofilm formation was inhibited, while 26% of the biofilm already formed was destroyed. These promising results validate our approach based on the development of bioactive-protein-loaded asymmetric membranes for antibiofilm strategies in situations where traditional antibiotic therapies are ineffective.