Plasma-activated antimicrobial hydrogel therapy (PAHT) for combatting infections in diabetic foot ulcers

等离子体激活抗菌水凝胶疗法 (PAHT) 用于对抗糖尿病足溃疡感染

• 批准号: EP/V00607X/1
• 负责人: Robert Short
• 金额: $ 72.42万
• 依托单位: Lancaster University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FV00607X%2F1
• 关键词: Plasma; activated; antimicrobial; hydrogel; therapy

In 2018 there were over 4.5 million people with diabetes in the UK, with this number expected to rise to 5 million by 2025. One of the most serious complications of diabetes is ulceration of the feet - a Diabetic Foot Ulcer (DFU). This is caused by a poor blood supply and nerve damage, meaning that patients cannot feel when they are starting to damage their feet by, for example, having poorly fitting shoes. Around 34% of patients with diabetes are likely to develop a DFU.Once a DFU is established it can rapidly become infected (50% likelihood); once infected it is difficult to treat, taking months or even years to heal. Soft tissue infection can lead to bone infection, which is really only treatable by amputation. By the time a patient's DFUs get to the stage of requiring amputation the prognosis for the patient is grim: 70% of patients with DFU-associated amputations are dead within 5 years.Infected DFUs are treated by antibiotics and surgical wound debridement: cutting away infected tissue. However antibiotics are becoming less effective, and with the rise of "superbugs" (known as antimicrobial resistance, AMR) infection will present a serious threat to anyone with an open wound. Consequently, there is an urgent need for non-antibiotic approaches for treating infected DFUs, to augment antibiotic treatment and to extend the "lifetime" of existing antibiotics (whilst new ones are developed).The clinical need is to treat infected DFUs at an earlier stage before bone infection takes hold. And in a manner that doesn't just kill the surface bacteria (and fungi), but reaches microorganisms buried deep within the dense slimy colonies (biofilms) in which the organisms live. Our novel technology is based upon utilising electrically-excited gases (known as cold atmospheric plasma, CAP) to create and deliver potent antimicrobial agents deep into infected wounds via interaction of the CAP with a wound dressing and the wound itself. Antimicrobial agents are released from wound dressings applied over the DFU. In this research project, we will develop this technology and demonstrate its potential in robust laboratory-based models of real-world biofilms that are found in DFUs. To ensure that this project realises the potential to deliver patient benefit (as soon as possible) we will map out how to assess the health economic benefits and the parameters needed for a robust clinical trial. We will engage with healthcare providers and patients early, and will achieve this through a range of outreach activities. This project is an important step in realising a novel technology treatment package that is cheap and easy to use, and which has the potential to greatly improve the care of patients with DFUs and decrease the need for amputation. This would improve patient quality of life, improve survival rates and save the NHS money.

2018年，英国有超过450万糖尿病患者，预计到2025年这一数字将增加到500万。糖尿病最严重的并发症之一是足部溃疡-糖尿病足溃疡（DFU）。这是由血液供应不足和神经损伤引起的，这意味着患者无法感觉到他们的脚开始受到伤害，例如，鞋子不合身。大约34%的糖尿病患者可能会发生DFU。一旦DFU建立，它可以迅速感染（50%的可能性）;一旦感染，就很难治疗，需要数月甚至数年才能治愈。软组织感染会导致骨感染，这实际上只能通过截肢来治疗。当患者的DFU达到需要截肢的阶段时，患者的预后是严峻的：70%的DFU相关截肢患者在5年内死亡。感染的DFU通过抗生素和手术伤口清创治疗：切除感染的组织。然而，抗生素的效果越来越差，随着“超级细菌”（称为抗菌素耐药性，AMR）的兴起，感染将对任何有开放性伤口的人构成严重威胁。因此，迫切需要用于治疗感染的DFU的非抗生素方法，以增加抗生素治疗并延长现有抗生素的“寿命”（同时开发新的抗生素）。临床需要在骨感染发生之前的早期阶段治疗感染的DFU。这种方式不仅能杀死表面的细菌（和真菌），还能杀死深埋在生物体所生活的稠密粘糊糊的菌落（生物膜）中的微生物。我们的新技术基于利用电激发气体（称为冷大气等离子体，CAP），通过CAP与伤口敷料和伤口本身的相互作用，产生并将强效抗菌剂深入感染伤口。抗菌剂从应用于DFU上的伤口敷料中释放。在这个研究项目中，我们将开发这项技术，并在DFU中发现的真实世界生物膜的强大实验室模型中展示其潜力。为了确保该项目实现为患者带来利益的潜力（尽快），我们将制定如何评估健康经济效益和稳健的临床试验所需的参数。我们将尽早与医疗服务提供者和患者接触，并将通过一系列外展活动实现这一目标。该项目是实现廉价且易于使用的新型技术治疗包的重要一步，并且有可能大大改善DFU患者的护理并减少截肢的需要。这将提高患者的生活质量，提高生存率，并节省NHS的资金。

项目成果

On Plasma Activated Acetyl Donors: Comparing the Antibacterial Efficacy of Tetraacetylethylenediamine and Pentaacetate Glucose

关于血浆激活的乙酰基供体：比较四乙酰乙二胺和五乙酸葡萄糖的抗菌功效

• DOI: 10.3390/plasma5040031
• 发表时间: 2022
• 期刊: Plasma
• 作者: Szili E

A conical assembly of six plasma jets for biomedical applications

• DOI: 10.1063/5.0104481
• 发表时间: 2022-08
• 期刊: Applied Physics Letters
• 影响因子: 4
• 作者: B. Ghimire;E. Szili;R. Short

Cold Plasma Generation of Peracetic Acid for Antimicrobial Applications

冷等离子体产生过氧乙酸用于抗菌应用

• DOI: 10.1615/plasmamed.2022041515
• 发表时间: 2021
• 期刊: Plasma Medicine
• 作者: Ghimire B

On-demand cold plasma activation of acetyl donors for bacteria and virus decontamination

• DOI: 10.1063/5.0062787
• 发表时间: 2021-08-02
• 期刊: APPLIED PHYSICS LETTERS
• 影响因子: 4
• 作者: Szili, Endre J.;Ghimire, Bhagirath;Short, Robert D.
• 通讯作者: Short, Robert D.

Cold Atmospheric Plasma-Activated Composite Hydrogel for an Enhanced and On-Demand Delivery of Antimicrobials.

• DOI: 10.1021/acsami.3c01208
• 发表时间: 2023-04-26
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Gaur, Nishtha;Patenall, Bethany L.;Ghimire, Bhagirath;Thet, Naing T.;Gardiner, Jordan E.;Le Doare, Krystal E.;Ramage, Gordon;Short, Bryn;Heylen, Rachel A.;Williams, Craig;Short, Robert D.;Jenkins, Toby A.
• 通讯作者: Jenkins, Toby A.