Controlling Catheter-Associated Urinary Tract Infections Using Smart Catheters with Rationally Designed Active Topographies

导管相关性尿路感染(CAUTI)是最常见的与医疗保健相关的 感染(HAI)，在美国的流行率为13-15%。CAUTIs也被指责为 受影响患者的发病率和死亡率增加，估计每年有13,000人死亡。它是 众所周知，非生物导管材料容易被微生物定植，然后这些微生物就会上升 导尿管通过运动和生物被膜形成，导致尿路感染。由于受到保护 对于生物膜基质和附着细胞生长缓慢的情况，生物膜细胞的抵抗力高达1,000倍 比同种类的浮游细胞对抗菌剂的作用更强。因此，CAUTI很难治疗，而且 导管管腔堵塞，特别是在长期使用时，会导致结石的形成。 以及膀胱甚至肾脏的感染。大剂量抗菌药物治疗冠脉感染 药物也会对多重耐药细菌的发展起到不利的促进作用。尽管广泛 到目前为止的研究表明，目前还没有一种技术可以提供长期(30天)的污垢控制。这是未满足的 挑战促使我们设计智能导管，最终根除CAUTI。 最近，PI的实验室开发了一种新的基于活动地形的防污策略，该策略可以驱动 磁感应微米大小的柱子，可用可调的频率和力水平敲打。这是 通过在每个柱子的尖端加载Fe3O4纳米颗粒并产生电磁脉冲来实现 使用嵌入导管壁内的绝缘铜线圈(因此不改变导管 简档)。这种新颖的设计展示了前所未有的强大的防污活性，可以抑制 多物种生物膜形成高达3.6Logs(99.98%)48小时，并去除成熟的生物膜 与平板控制相比，按需增加高达3.5个原木(99.97%)，具有更强的作用力。原型机 内壁有微米大小柱子的导尿管被设计出来，保持清洁30多年 在人工尿流和致尿性大肠杆菌(UPEC)的挑战下的天数，而 UPEC生物膜在5天内完全封闭了扁平对照和静态对照。这些结果 激励团队进一步开发这项技术，以控制外导管壁的生物污垢， 它被尿路黏膜覆盖，累及三分之二的CAUTIs。集成仿真和 将进行实验研究，以了解活性物质控制生物污染的机理。 导管壁两侧的地形和防污地形的设计原则。这个 最好的设计将用UPEC诱导的CAUTI兔模型在体内进一步测试。两者都是CAUTI 将对已建立的生物膜的预防(最多30天)和清除进行评估。

Catheter associated urinary tract infection (CAUTI) is one of the most common healthcare-associated infections (HAIs), with a prevalence of 13 – 15% in the United States. CAUTIs are also blamed for increased morbidity and mortality of affected patients with an estimated 13,000 deaths annually. It is well known that the abiotic catheter materials are prone to colonization of microbes, which then ascend the catheter via motility and biofilm formation, causing infections in the urinary tract. Due to the protection of the biofilm matrix and slow growth of attached cells, biofilm cells are up to 1,000 times more resistant to antimicrobials than the planktonic cells of the same species. Thus, CAUTIs are difficult to treat and blockage of the catheter lumen can occur especially during long-term use, leading to stone formation and infections of the bladder and even kidney. Treatment of CAUTIs with high doses of antimicrobial agents can also adversely promote the development of multidrug resistant bacteria. Despite extensive research to date, no current technology can provide long-term (>30 days) fouling control. This unmet challenge motivated us to engineer smart catheters to ultimately eradicate CAUTI. Recently, the PI’s lab developed a new antifouling strategy based on active topography that drives magnetically responsive micron-size pillars to beat with a tunable frequency and force level. This was achieved by loading Fe3O4 nanoparticles on the tip of each pillar and generating an electromagnetic field using an insulated copper coil embedded in the catheter wall (thus does not change the catheter profile). This novel design demonstrated unprecedented strong antifouling activities that can inhibit biofilm formation of multiple species by up to 3.6 logs (99.98%) for 48 hours and remove mature biofilms by up to 3.5 logs (99.97%) on demand with a stronger force, compared to the flat control. A prototype catheter with micron-size pillars on the inner wall was engineered and remained clean for more than 30 days under the flow of artificial urine and the challenge of uropathogenic Escherichia coli (UPEC), while both flat and static controls were completely blocked by UPEC biofilms within 5 days. These results motivated the team to further develop this technology to also control biofouling of the outer catheter wall, which is covered by urethral mucosa and involved in two thirds of CAUTIs. Integrated simulation and experimental studies will be conducted to understand the mechanism of biofouling control by active topography and the design principles for antifouling topographies on both sides of the catheter wall. The best design will be further tested in vivo using a rabbit model of CAUTI induced by UPEC. Both CAUTI prevention (up to 30 days) and removal of established biofilms will be evaluated.