Riool Martijn, de Breij Anna, Drijfhout Jan W, Nibbering Peter H, Zaat Sebastian A J
Department of Medical Microbiology, Academic Medical Center, Amsterdam Infection and Immunity Institute, University of AmsterdamAmsterdam, Netherlands.
Department of Infectious Diseases, Leiden University Medical CenterLeiden, Netherlands.
Front Chem. 2017 Aug 24;5:63. doi: 10.3389/fchem.2017.00063. eCollection 2017.
Over the past decades the use of medical devices, such as catheters, artificial heart valves, prosthetic joints, and other implants, has grown significantly. Despite continuous improvements in device design, surgical procedures, and wound care, biomaterial-associated infections (BAI) are still a major problem in modern medicine. Conventional antibiotic treatment often fails due to the low levels of antibiotic at the site of infection. The presence of biofilms on the biomaterial and/or the multidrug-resistant phenotype of the bacteria further impair the efficacy of antibiotic treatment. Removal of the biomaterial is then the last option to control the infection. Clearly, there is a pressing need for alternative strategies to prevent and treat BAI. Synthetic antimicrobial peptides (AMPs) are considered promising candidates as they are active against a broad spectrum of (antibiotic-resistant) planktonic bacteria and biofilms. Moreover, bacteria are less likely to develop resistance to these rapidly-acting peptides. In this review we highlight the four main strategies, three of which applying AMPs, in biomedical device manufacturing to prevent BAI. The first involves modification of the physicochemical characteristics of the surface of implants. Immobilization of AMPs on surfaces of medical devices with a variety of chemical techniques is essential in the second strategy. The main disadvantage of these two strategies relates to the limited antibacterial effect in the tissue surrounding the implant. This limitation is addressed by the third strategy that releases AMPs from a coating in a controlled fashion. Lastly, AMPs can be integrated in the design and manufacturing of additively manufactured/3D-printed implants, owing to the physicochemical characteristics of the implant material and the versatile manufacturing technologies compatible with antimicrobials incorporation. These novel technologies utilizing AMPs will contribute to development of novel and safe antimicrobial medical devices, reducing complications and associated costs of device infection.
在过去几十年中,诸如导管、人工心脏瓣膜、假体关节及其他植入物等医疗设备的使用显著增加。尽管设备设计、外科手术及伤口护理不断改进,但生物材料相关感染(BAI)仍是现代医学中的一个主要问题。由于感染部位抗生素浓度较低,传统的抗生素治疗往往失败。生物材料上生物膜的存在和/或细菌的多重耐药表型进一步削弱了抗生素治疗的效果。移除生物材料成为控制感染的最后手段。显然,迫切需要替代策略来预防和治疗BAI。合成抗菌肽(AMPs)被认为是有前景的候选物,因为它们对多种(耐抗生素的)浮游细菌和生物膜具有活性。此外,细菌对这些速效肽产生耐药性的可能性较小。在本综述中,我们重点介绍了生物医学设备制造中预防BAI的四种主要策略,其中三种应用了AMPs。第一种策略涉及改变植入物表面的物理化学特性。第二种策略是通过多种化学技术将AMPs固定在医疗设备表面。这两种策略的主要缺点是植入物周围组织中的抗菌效果有限。第三种策略通过以可控方式从涂层中释放AMPs来解决这一局限性。最后,由于植入物材料的物理化学特性以及与抗菌剂掺入兼容的通用制造技术,AMPs可集成到增材制造/3D打印植入物的设计和制造中。这些利用AMPs的新技术将有助于开发新型且安全的抗菌医疗设备,减少设备感染的并发症及相关成本。