Antimicrobial Bandages for the Treatment of Wound Infections

感染是闭合性手术伤口、创伤和烧伤伤口以及慢性皮肤溃疡延迟愈合的主要原因。伤口感染控制是一个有争议的问题，特别是在抗菌素耐药性（AMR）流行的背景下。此外，伤口感染的治疗是NHS资源和患者生活质量的重大经济负担。敷料和绷带在现代伤口管理中发挥着重要作用，含银敷料是皮肤伤口最常用的敷料。虽然这些治疗方法在减少微生物负担方面取得了很大进展，但可能存在减少感染所需的高浓度银的潜在细胞毒性问题。一氧化氮（NO）是一种有效的抗菌剂，在伤口修复中已被证明具有重要作用，这使其成为治疗伤口感染的绝佳候选者。该HIP的目的是通过将NO释放银纳米颗粒（NP）嵌入到最先进的原型绷带中来改进当前的银技术，该原型绷带将利用NO的双重伤口修复和抗菌功能。这些纳米颗粒是在epsrc之前资助的资金（EP/M027325/1工程一氧化氮输送平台用于伤口愈合应用）下开发的，我们已经证明，释放一氧化氮的纳米颗粒在杀死高浓度细菌方面非常有效。该提案以这项工作为基础，采用“个性化药物”方法，在治疗皮肤和眼睛感染的不同配方中调整NO的释放率和浓度。我们汇集了在皮肤伤口感染和愈合以及眼表伤口感染和愈合方面具有特定和互补技能的临床项目合作伙伴。我们的商业合作伙伴包括一家世界领先的美国公司，专门从事纳米材料的制造、表征和集成到产品和系统中，以及一家位于英国的中小企业，该企业在体外重建皮肤技术方面处于领先地位，正在创新护肤研发。通过这一合作，我们将开发抗菌NO释放纳米颗粒的临床适用性、技术和商业可行性，并将其纳入绷带中，以加速拟议研究的从实验室到临床的影响。no释放纳米颗粒将被制造和优化，以提供治疗的控制和持续释放。我们已经成功地将NO释放官能团拴在银和金纳米颗粒上，并控制NO的有效载荷。这些首先连接到一个高分子量的聚合物涂层，然后聚合物被共轭到粒子上，以确保高稳定性。我们会控制排放计划的大小和形状，以优化排放速度和特定地点产生的一氧化氮量。所有NP制剂将评估其对临床相关细菌和真菌菌株的抗菌活性及其细胞相容性。然后，这些纳米粒子将被嵌入到由静电纺聚氨酯、海藻酸盐或肽水凝胶制成的原型绷带中，这取决于它们在皮肤或角膜伤口上的潜在应用。含NO释放NPs的绷带的有效性将通过体外实验和离体和离体3D模型进行测试。这项技术的发展提供了可持续的、有效的和经济的解决办法，而不会助长抗菌素耐药性的流行，同时参与科学上优秀的、与工业相关的研究。

Infection is the main cause of delayed healing in closed surgical wounds, traumatic and burn wounds, and chronic skin ulcers. Infection control for wounds is a contentious issue, particularly against a background of the antimicrobial resistance (AMR) epidemic. Furthermore, treatment of wound infections represents a significant economic burden on NHS resources and the quality of life of patients. Dressings and bandages have a major part to play in the modern management of wounds, with silver-containing dressings being the most commonly used for skin wounds. While these treatments have made great strides in reducing microbial bioburden, there may be potential cytotoxic issues regarding high concentrations of silver needed for reducing infection.Nitric oxide (NO) is a potent antimicrobial agent and has a proven role in wound repair which makes it an excellent candidate for the treatment of wound infections. The aim of this HIP is to improve upon the current silver technologies by embedding NO releasing silver nanoparticles (NP) into state of the art prototype bandages that will exploit NO's dual wound repair and antimicrobial function. These nanoparticles have been developed with previous EPSRC-funded funding (EP/M027325/1 Engineering Nitric Oxide Delivery Platforms for Wound Healing Applications) and we have shown the NO releasing nanoparticles to be extremely potent at killing bacteria present at very high concentrations. This proposal builds on this work by taking on a "personalised medicine" approach and tailoring release rates and concentrations of NO in different formulations for treating infections in the skin and eye. We have brought together clinical project partners with specific and complementary skills in skin wound infection and healing, and surface ocular wound infection and healing. Our commercial partners include a world leading US company that specialises in the fabrication, characterisation, and integration of nanomaterials into products and systems and a UK based SME that is at the forefront of reconstructed in vitro skin technologies that is innovating skincare research and development. Through this partnership, we will develop the clinical applicability, and the technical and commercial viability of antimicrobial NO releasing nanoparticles and their incorporation into bandages to accelerate the bench-to-clinic impact of the proposed research. NO-releasing nanoparticles will be fabricated and optimised to deliver a controlled and sustained release of the therapeutic. We have successfully tethered NO releasing functional groups to silver and gold nanoparticles with control over NO payload. These are first linked to a high molecular weight polymer coatings and then the polymer is conjugated to the particle to ensure high stability. We will optimise the rate of delivery and the amount of site-specific generated NO by controlling the size and shape of the NPs. All NP preparations will be evaluated for their antimicrobial activity against clinically relevant bacterial and fungal strains and their cytocompatibility. These nanoparticles will then be embedded into prototype bandages made from either electrospun polyurethane and alginate or peptide hydrogels depending on their potential application to skin or corneal wounds, respectively. The efficacy of the bandages containing the NO releasing NPs will be tested in in vitro assays and in ex vivo and in vitro 3D models. The development of this technology offers sustainable effective and economic solutions without contributing to the AMR epidemic while simultaneously participating in scientifically excellent, industrially relevant research.