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用于治疗和预防细菌感染的局部噬菌体递送

Local Bacteriophage Delivery for Treatment and Prevention of Bacterial Infections.

作者信息

Rotman Stijn Gerard, Sumrall Eric, Ziadlou Reihane, Grijpma Dirk W, Richards Robert Geoff, Eglin David, Moriarty Thomas Fintan

机构信息

AO Research Institute Davos, AO Foundation, Davos, Switzerland.

MIRA Institute for Biomedical Engineering and Technical Medicine, Department of Biomaterials Science and Technology, University of Twente, Enschede, Netherlands.

出版信息

Front Microbiol. 2020 Sep 18;11:538060. doi: 10.3389/fmicb.2020.538060. eCollection 2020.

Abstract

As viruses with high specificity for their bacterial hosts, bacteriophages (phages) are an attractive means to eradicate bacteria, and their potential has been recognized by a broad range of industries. Against a background of increasing rates of antibiotic resistance in pathogenic bacteria, bacteriophages have received much attention as a possible "last-resort" strategy to treat infections. The use of bacteriophages in human patients is limited by their sensitivity to acidic pH, enzymatic attack and short serum half-life. Loading phage within a biomaterial can shield the incorporated phage against many of these harmful environmental factors, and in addition, provide controlled release for prolonged therapeutic activity. In this review, we assess the different classes of biomaterials (i.e., biopolymers, synthetic polymers, and ceramics) that have been used for phage delivery and describe the processing methodologies that are compatible with phage embedding or encapsulation. We also elaborate on the clinical or pre-clinical data generated using these materials. While a primary focus is placed on the application of phage-loaded materials for treatment of infection, we also include studies from other translatable fields such as food preservation and animal husbandry. Finally, we summarize trends in the literature and identify current barriers that currently prevent clinical application of phage-loaded biomaterials.

摘要

作为对其细菌宿主具有高度特异性的病毒,噬菌体是一种有吸引力的根除细菌的手段,其潜力已得到广泛行业的认可。在病原菌抗生素耐药率不断上升的背景下,噬菌体作为一种可能的治疗感染的“最后手段”策略受到了广泛关注。噬菌体在人类患者中的应用受到其对酸性pH值、酶攻击和血清半衰期短的敏感性的限制。将噬菌体负载在生物材料中可以保护所含噬菌体免受许多这些有害环境因素的影响,此外,还能提供控释以延长治疗活性。在本综述中,我们评估了用于噬菌体递送的不同类别的生物材料(即生物聚合物、合成聚合物和陶瓷),并描述了与噬菌体嵌入或封装兼容的加工方法。我们还详细阐述了使用这些材料产生的临床或临床前数据。虽然主要重点是负载噬菌体的材料在治疗感染中的应用,但我们也纳入了其他可转化领域的研究,如食品保鲜和畜牧业。最后,我们总结了文献中的趋势,并确定了目前阻碍负载噬菌体的生物材料临床应用的障碍。

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