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.

中文翻译：

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设计具有抗生物膜特性的伤口敷料可生物降解的基于PHA的3D支架：微结构/纳米结构的优化

抑制自然伤口愈合过程的一个主要因素是通过细菌生物膜的感染，特别是在慢性伤口的情况下。在这项研究中，伤口敷料的微观/纳米结构得到了优化，以便获得更有效的抗生物膜蛋白释放曲线，以抑制和/或分离生物膜。用不对称的聚羟基链烷酸酯（PHA）膜开发了3D底物，以捕获抗生物膜蛋白Dispersin B（DB）。使用湿诱导相分离（WIPS）制备膜。通过调节致孔剂聚合物聚乙烯吡咯烷酮（PVP）的浓度和分子量，制得了具有可控孔隙率的不对称膜。相对于总聚合物浓度，以10、30和50％w / w的比例添加PVP。研究了四元非溶剂/溶剂/ PHA / PVP体系的物理和动力学性质，并将其与获得的膜结构相关联。结果表明，在高分子量（M _w = 360 kDa）和高PVP含量（超过30％），孔径减小，膜变得非常脆，物理完整性严重受损。对于低分子量PVP（M _w = 40 kDa），在可比较的含量下未观察到这种脆性作用。无论分子量如何，成孔剂含量最多可增加30％，从而增加膜表面孔隙率，从而增加蛋白质摄入量。超过30％的成孔剂含量，孔径和物理完整性/机械强度均降低。PHA膜上装有DB，并评估了它们对表皮葡萄球菌生物膜的抗生物膜活性。当细菌生物膜暴露于装有DB的PHA膜上时，表皮葡萄球菌最多可占33％生物膜形成受到抑制，而已经形成的生物膜中有26％被破坏。这些有希望的结果验证了我们在基于传统抗生素疗法无效的情况下基于生物活性蛋白不对称膜开发抗生物膜策略的方法的有效性。