Self-triggered smart biomaterials

自触发智能生物材料

• 批准号: 2442958
• 金额: --
• 依托单位: Queen's University Belfast
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2442958
• 关键词: Self; triggered; smart; biomaterials

Polymeric biomaterials, which are typically synthetic substances introduced into body tissue as part of an implanted medical device or used to replace an organ or bodily function, are increasingly ubiquitous in healthcare. The introduction of biomaterials brings with it a risk of infection from microorganisms, representing a major risk to patients and burden to the NHS requiring extended, complex treatments, which are often unsuccessful. With infection rates approaching 100% in some devices, there is an urgent unmet need to develop ways to prevent bacterial biofilms forming on the surface of medical devices.Typically, infection involves initial attachment of bacteria to the surface of the biomaterial, followed by colonisation through subdivision and growth into a biofilm. This biofilm is highly resistant to treatment by antibiotics, and acts as a reservoir for further spread of infection in the body. This can lead to sepsis and death. To effectively address the problem of biofilm development in biomaterials, this project has two key aims in the development of smart materials-those which are responsive to a stimulus such as light (applied externally) or the onset of infection (where the stimulus is internal).Firstly, we seek to build on a previous EPSRC project, and some further recent results from our lab, which represents a new way to kill any bacteria which may still be able to attach to the polymer. This uses a combination of visible light and photosensitisers - a class of molecule which can use light to catalytically produce reactive oxygen, which is highly effective at killing bacteria. A key point in using this chemistry is that the range of active species are able to attack a wide range of targets in bacteria, rather than a single mode of action, which is a limitation of traditional approaches, such as antibiotics. As such, the approach gets round the issue of development of antimicrobial resistance, and has a long lived effect, which should allow it to be supported by clinicians in the future.In this strand, we will use synthetic chemistry, materials science and engineering methods in extrusion to develop new ways to incorporate photosensitisers at the direct point of bacterial attachment - the medical device surface. We will use multi-layered extrusion techniques to make thin coatings on substrates used to manufacture traditional medical devices, such as PVC. We will tune the efficiency of this system to maximise production of reactive oxygen, and carry out a full chemical and physical characterisation of the light-induced processes and how effectively they kill bacteria. Secondly, in a linked approach, we will build on interesting recent results which show we can use pH to control rate of cleavage of a model drug substance from a polymer suitable for use in medical device applications. A change in pH is observed at the onset of infection in urinary catheter infections in particular, so there is an opportunity to develop materials which are able to kill a bacterial infection in response to its own development, thereby stopping the infection in its tracks. Using synthetic chemistry, we will develop new 'building blocks' for polymers which can be used to make a responsive coating to a current medical device material. This will allow us to engineer polymers which are inherently able to resist the attachment of bacteria. In practice, this involves polymer synthesis to make our new candidate materials, then characterising their surface chemistry using a range of spectroscopic, microscopic and physical methods. We will then assess the ability of the materials to resist bacterial attachment by trying to grow biofilms of bacteria which typically cause infections.Together this will allow us to develop materials which may be incorporated in or on medical devices such as endotracheal tubes, urinary catheters, or intraocular lenses, which would have wide impact for patients and medical device companies.

聚合物生物材料通常是作为植入医疗器械的一部分引入身体组织或用于替代器官或身体功能的合成物质，在医疗保健中越来越普遍。生物材料的引入带来了微生物感染的风险，这对患者构成了重大风险，并给NHS带来了负担，需要长期复杂的治疗，但往往不成功。随着一些医疗器械的感染率接近100%，迫切需要开发防止细菌生物膜在医疗器械表面形成的方法。通常，感染涉及细菌最初附着在生物材料表面，然后通过细分和生长成生物膜而定殖。这种生物膜对抗生素治疗具有高度抗性，并作为体内感染进一步传播的水库。这可能导致败血症和死亡。为了有效地解决生物材料中生物膜发展的问题，该项目在智能材料的开发方面有两个关键目标-那些对光等刺激反应的材料（外部应用）或感染开始（其中刺激是内部的）。首先，我们寻求建立在以前的EPSRC项目，以及我们实验室最近的一些结果，这代表了一种杀死任何可能仍然能够附着在聚合物上的细菌的新方法。这种方法结合了可见光和光敏剂，光敏剂是一类可以利用光催化产生活性氧的分子，活性氧在杀死细菌方面非常有效。使用这种化学物质的一个关键点是，活性物质的范围能够攻击细菌中的各种靶标，而不是单一的作用模式，这是传统方法的局限性，如抗生素。因此，这种方法避免了抗生素耐药性的产生，并且具有长期的效果，这应该使它在未来得到临床医生的支持。在这一链中，我们将使用合成化学，材料科学和挤出工程方法来开发新的方法，将光敏剂引入细菌附着的直接点-医疗器械表面。我们将使用多层挤出技术在用于制造传统医疗器械（如PVC）的基材上制作薄涂层。我们将调整该系统的效率，以最大限度地产生活性氧，并对光诱导过程进行全面的化学和物理表征，以及它们如何有效地杀死细菌。其次，在一种相关方法中，我们将建立在最近有趣的结果基础上，这些结果表明我们可以使用pH值来控制模型原料药从适用于医疗器械应用的聚合物中裂解的速率。特别是在导尿管感染的感染开始时观察到pH的变化，因此有机会开发能够响应细菌感染自身的发展而杀死细菌感染的材料，从而阻止感染。使用合成化学，我们将开发新的聚合物“积木”，可用于制造当前医疗器械材料的响应涂层。这将使我们能够设计出固有地能够抵抗细菌附着的聚合物。在实践中，这涉及到聚合物合成，使我们的新候选材料，然后使用一系列光谱，显微镜和物理方法表征其表面化学。然后，我们将通过培养细菌生物膜来评估材料抵抗细菌附着的能力，这些细菌通常会引起感染。这将使我们能够开发出可用于气管内导管、导尿管或人工晶状体等医疗器械的材料，这将对患者和医疗器械公司产生广泛的影响。