3D Printed, Stand-alone, Colourimetric Indicator Strip (3DCIS) for Non-Invasive, On-demand Chronic Wound Monitoring

慢性伤口被称为“无声的流行病”，在其一生中影响很大比例的人口，占1- 2%。慢性伤口的主要原因是：糖尿病、烧伤和压疮，正如“慢性”一词所暗示的那样，这些伤口不容易治愈。因此，在最近的一项研究中，近42%的腿/足溃疡在过去的6个月内没有愈合，28%的人在一年或更长时间内没有愈合。在所有国家，慢性伤口护理给地方和国家保健服务造成相当大的负担。例如，在英国，大约有65万名患者患有某种形式的慢性伤口，每年的费用约为30亿英镑，而在美国，大约有650万名患者，每年的治疗费用约为250亿英镑。静脉溃疡，通常发生在腿部，占慢性伤口的70-90%，大多影响老年人。由此可见，由于全球平均预期寿命持续上升，慢性伤口的发病率和治疗费用也将持续上升。英国国家医疗服务体系每年用于治疗这些疾病的总费用约为30亿英镑。显然需要一种廉价的一次性伤口监测方法，这种方法可以：(i)很容易地结合到伤口敷料中，从而使其变得智能；（ii）能够为临床医生、护士和患者提供关于关键生物标志物的连续或半连续信息流，即生化线索，这将有助于识别伤口的状况/状态，从而标记出无法正常愈合和需要医疗干预的伤口。所提出的技术涉及多分析物条带的3D打印，该条带由四种不同的基于颜色的指示器组成，这些指示器可选择性地响应四种不同的气体生物标记物，即：CO2，挥发性胺（RNH2），湿度（H2O）和O2。这条将提供一个半连续的，按需的信息流，关于伤口上方和敷料所包含的头部空间的成分。与现有的伤口监测方法相比，这种简单、独立的彩色条带所提供的多分析物原位挥发性分析具有许多优点，其中包括：(1)使用3D打印技术完成条带生产，(2)可以通过眼睛或数码相机读取的简单颜色变化，(3)简单地合并到现有的伤口敷料中（即独立），(4)易于解释，(5)记录数据趋势和自动实时警报(6)便宜，(7)非接触/非侵入性，(8)适用于广泛的医疗保健环境(包括：(9)适用于其他领域，包括医疗领域，如急性伤口敷料和非医疗领域，如食品和电子产品包装，（10）适用于微加工，（11）可添加其他分析物的范围，如温度和挥发性硫化物。

Chronic wounds have been referred to as the 'silent epidemic' that affects a significant proportion, 1-2 %, of the population during their lifetime. The main causes of chronic wounds are: diabetes, burns and pressure ulcers and, as the term 'chronic' suggests, they are not readily cured. Thus, in a recent study almost 42% of leg/foot ulcers had not healed in the previous 6 months and 28% had remained unhealed for a year or longer. In all countries, chronic woundcare places a considerable burden upon the local and national health services. For example, in the UK, some 650,000 patients suffer from some form of chronic wound, resulting in an annual cost of ca. £3 Bn, and in the USA there are about 6.5 M suffers, whose treatment costs ca. £25 Bn pa. Venous ulcers, which usually occur in the legs, account for 70-90% of chronic wounds and mostly affect the elderly. It follows that since the global average life expectancy continues to rise then so too will the number of incidences, and cost, of treatment of chronic wounds. The combined cost to the NHS for their treatment reaches approximately £3 billion per year. There is a clear need for an inexpensive, disposable wound monitoring method that can be: (i) readily incorporated into a wound dressing, thereby rendering it smart and, (ii) able to provide clinicians, nurses and patients with a continuous, or semi-continuous, stream of information about key biomarkers, i.e. biochemical cues, which would help identify the condition/status of the wound and so flag up wounds that are not healing properly and that require medical intervention. The proposed technology involves the 3D printing of a multi-analyte strip, comprised of four different colour-based indicators which are selective in response to four different gaseous bio-markers, namely: CO2, volatile amines (RNH2), humidity (H2O) and O2. This strip will provide a semi-continuous, on-demand, stream of information concerning the composition of the headspace above the wound and contained by the dressing. The proposed multi-analyte, in situ, volatile analysis, afforded by this simple, stand-alone, colour strip, has a number of advantages compared to existing wound monitoring methods, which include: (1) complete strip production using 3D printing technology, (2) simple colour changes that can be read by eye or digital camera, (3) simple to incorporate into an existing wound dressing (i.e. stand-alone), (4) easy to interpret, (5) logged data trends and automatic real-time alerts (6) inexpensive, (7) non-contact/non-invasive, (8) applicable in a wide number of healthcare environments (including: point of care, outpatients, hospital wards and home care), (9) scope for application in other areas, both medical, such as in acute wound dressings, and non-medical, such as food and electronic goods packaging, (10) amenable to microfabrication and (11) scope for other analytes to be added, such as temperature and volatile sulfides.