Department of Polymer Science, University of Akron, Akron, OH 44325, United States.
Cook Research Inc., West Lafayette, IN 47906, United States.
Biomaterials. 2018 Sep;178:339-350. doi: 10.1016/j.biomaterials.2018.05.010. Epub 2018 May 11.
The use of catheters is ubiquitous in medicine and the incidence of infection remains unacceptably high despite numerous advances in functional surfaces and drug elution. Herein we report the use of a thermoplastic polyurethane containing an allyl ether side-chain functionality (allyl-TPU) that allows for rapid and convenient surface modification with antimicrobial reagents, post-processing. This post-processing functionalization affords the ability to target appropriate TPU properties and maintain the functional groups on the surface of the device where they do not affect bulk properties. A series of quaternary ammonium thiol compounds (Qx-SH) possessing various hydrocarbon tail lengths (8-14 carbons) were synthesized and attached to the surface using thiol-ene "click" chemistry. A quantitative assessment of the amount of Qx-SH available on the surface was determined using fluorescence spectroscopy and X-ray photoelectron spectroscopy (XPS). Contact-killing assays note the Q8-SH composition has the highest antimicrobial activity, and a live/dead fluorescence assay reveals rapid contact-killing of Staphylococcus aureus (>75% in 5 min) and Escherichia coli (90% in 10 min) inocula. Scale-up and extrusion of allyl-TPU provides catheter prototypes for biofilm formation testing with Pseudomonas aeruginosa, and surface-functionalized catheters modified with Q8-SH demonstrate their ability to reduce biofilm formation.
导管在医学中应用广泛,尽管在功能表面和药物洗脱方面取得了许多进展,但感染的发生率仍然高得令人无法接受。在此,我们报告了使用一种含有烯丙基醚侧链官能团的热塑性聚氨酯(allyl-TPU),它允许快速方便地用抗菌试剂进行表面后处理修饰。这种后处理功能化赋予了靶向适当的 TPU 特性的能力,并保持了官能团在设备表面上,而不会影响其体积特性。合成了一系列具有不同碳氢链长度(8-14 个碳原子)的季铵硫醇化合物(Qx-SH),并使用硫醇-烯“点击”化学将其连接到表面上。使用荧光光谱法和 X 射线光电子能谱(XPS)定量评估了表面上可用的 Qx-SH 量。接触杀伤试验表明,Q8-SH 组成具有最高的抗菌活性,活/死荧光试验表明金黄色葡萄球菌(5 分钟内>75%)和大肠杆菌(10 分钟内 90%)接种物的快速接触杀伤。烯丙基 TPU 的放大和挤出提供了用于铜绿假单胞菌生物膜形成测试的导管原型,并用 Q8-SH 修饰的表面功能化导管证明了它们减少生物膜形成的能力。