Institute of Chemical Engineering, National Taipei University of Technology, 1, Sec 3, Zhongxiao E Rd, Taipei 106, Taiwan.
Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
J Control Release. 2021 Mar 10;331:154-163. doi: 10.1016/j.jconrel.2021.01.024. Epub 2021 Jan 18.
To combat the emergence of drug-resistant bacteria, a locally isolated bacteriophage (HZJ) targeting H5α Escherichia coli was used as an antibacterial agent to make wound dressing samples in this study. The phages were physically embedded within an alginate hydrogel sample so that they could later be released with their tails being free during the infection process, which preserves their lytic activity. The HZJ phage isolated in the study have a 20 min latent period and are stable between pH 6 and pH 9 and at temperatures below 45 °C. The addition of phage to an E. coli culture suppressed over 99% of bacterial growth in 2-h (p < 0.001). Phage-embedded hydrogel fibers were used to create porous wound dressing material using three-dimensional (3D) printing. The majority of phage lytic activity (85%-90%) was preserved after encapsulation. After they were embedded in samples, HZJ lysed 57% to 67% of bacteria (p < 0.001) within 2 h and the antibacterial effects lasted at least 24 h. The small amount of phage released in 2 h was able to quickly replicate and effectively lysed the majority of the bacterial hosts. Phage-embedded alginate samples released 10% of its incorporated phage particles in 24 h. The SEM micrographs show that, compared to phage-free samples, fewer E.coli cells were observed on phage-embedded samples 2 h after bacteria were exposed to the samples. The phage-embedded sample was not cytotoxic to L929 cells. The presence of HZJ in alginate hydrogel promoted cell growth (p < 0.01) and adhesion to the samples. Further, the existence of phage did not alter the tensile strength and modulus of samples (p > 0.05). An antibacterial dressing capable of slowly releasing lytic phages and effectively suppressing bacterial growth for up to 24 h was produced in this study. This model represents an attractive means to reduce use of antibiotics and other additives in conventional dressings.
为了应对耐药菌的出现，本研究使用一种针对 H5α 大肠杆菌的本地分离噬菌体（HZJ）作为抗菌剂来制备伤口敷料样品。噬菌体被物理嵌入藻酸盐水凝胶样品中，以便在感染过程中随着尾巴的自由释放，保持其裂解活性。在研究中分离的 HZJ 噬菌体潜伏期为 20 分钟，在 pH6 到 pH9 之间以及低于 45°C 的温度下稳定。噬菌体的添加抑制了大肠杆菌培养物中超过 99%的细菌生长，在 2 小时内（p<0.001）。噬菌体嵌入水凝胶纤维用于使用三维（3D）打印创建多孔伤口敷料材料。噬菌体的大多数裂解活性（85%-90%）在封装后得到保留。将 HZJ 嵌入样品后，在 2 小时内裂解了 57%-67%的细菌（p<0.001），并且抗菌效果至少持续 24 小时。在 2 小时内释放的少量噬菌体能够快速复制并有效地裂解大多数细菌宿主。在 24 小时内，嵌入藻酸盐的噬菌体样品释放了其结合的噬菌体颗粒的 10%。SEM 显微照片显示，与不含噬菌体的样品相比，暴露于样品 2 小时后，嵌入噬菌体的样品上观察到的大肠杆菌细胞数量减少。噬菌体嵌入样品对 L929 细胞没有细胞毒性。HZJ 存在于藻酸盐水凝胶中促进了细胞生长（p<0.01）和对样品的粘附。此外，噬菌体的存在并没有改变样品的拉伸强度和模量（p>0.05）。本研究制备了一种能够缓慢释放裂解噬菌体并有效抑制细菌生长长达 24 小时的抗菌敷料。这种模型代表了一种有吸引力的方法，可以减少传统敷料中抗生素和其他添加剂的使用。
