Intelligent Patches for Wound Management and Healing

Intelligent wound patches overcome the drawbacks associated with traditional wound dressings, by introducing on-demand wound visualisation, biosensing, pH and temperature control, glucose detection and controlled drug release, which have the potential to accelerate healing in chronic wounds.?

Skin plays an integral role in the human body,?by providing protection, moisture and temperature control, as a sensory organ, etc. Factors such as injury or disease can damage this protective barrier and therefore affect its normal functioning.?Skin typically heals on its own, following a complex four-stage process from haemostasis to inflammation, proliferation and then regeneration. This occurs when the tissue and cellular environment is ideal to promote healing, and this isn’t normally the case, resulting in chronic wounds. Chronic wounds cannot heal on their own, due to various pathological factors such as high glucose, lack of related growth factors, vascular diseases, etc. This delayed healing makes the wound prone to further infection by bacterial pathogens, thus leaving the wound in a constant inflammatory state, which can potentially affect the patient’s health. This brings about the need for timely and effective wound management for chronic wounds, to accelerate healing, minimize infection and relieve the patient’s pain.?

Traditional wound dressings are still the go-to approach when managing chronic wounds. They have proven effective, by covering and protecting the wound from further injury or infection as well as absorbing the wound exudate. However, these dressings cannot monitor and control infection within the wound, and also run the risk of damaging newly formed tissue during dressing changes. There is therefore a need for an intelligent wound dressing that can provide real-time wound monitoring, as well as deliver drugs to the wound in a controlled and precise manner, to prevent cellular drug resistance. Smart dressings/ patches have been developed in recent years, and are able to provide drug release, wound monitoring, and biosensing, all in one non-invasive and disposable piece of wearable technology. This comes at a time when the demand for medical big data and more personalized and precise medical care is at an all-time high. In this review, we will look at the recent developments in these wound dressings, and the features that make them ‘intelligent’, such as biosensing and electronic assistance healing.?

In Situ Monitoring?

In situ monitoring of wounds seeks to tackle the most common wound complication, infection, through timely monitoring of the wound environment in order to provide on-demand treatment.?

Visualisation Sensing: This is the use of highly transparent wound dressing materials, which enables the constant visualisation of the changes happening within the wound area at any given time. This reduces the frequency of dressing changes and therefore minimizes the risk of infection. One example is the superclear patch which is prepared with chitosan-coated cellulose membranes and enables real-time monitoring of wound healing.?

Potential Hydrogen (pH) Sensing: The pH of the epidermis is a key indicator of the skin’s condition at any given time. Epidermal pH is related to angiogenesis, protease activity as well as bacterial infection, and therefore, regular monitoring of the wound pH can provide great insight and guide treatment and healing. The pH of healthy skin ranges from 4 to 6 and tends towards alkalinity in an unhealed wound. Increases in pH typically indicate a possible bacterial infection due to the alkaline by-products produced by bacteria. Being able to detect these changes as they happen allows timely treatment. This is done through the implementation of pH sensors within the biomaterial dressings. pH sensors can range from pH-responsive dyes to pH-sensitive colour changing reaction materials and luminescent dyes, and incorporating these within transparent dressings can provide both wound visualisation and pH monitoring. Smart devices are then used to take pictures of these colour changes, which can then convert this visual information to quantitative data (Fig 1).?

Glucose Monitoring: Diabetic ulcers are a common type of chronic wound that affects about 20% of all diabetic patients. The higher blood sugar levels in these patients provide a conducive environment for bacterial growth within the wound, which in turn negatively affects healing. Therefore,?the blood sugar level is a critical factor that reflects the physical conditions of diabetic patients, and the state of diabetic wounds can be effectively?reflected by the concentration of blood glucose. Monitoring blood glucose can be done using fluorescence, where glucose-sensitive enzymes produce fluorescent products that can then be detected using optical sensors within a smart device (Fig 1).?

Figure 1: Sensing and monitoring of pH and glucose levels by a biosensing patch and a smartphone.?

Temperature Sensing: Temperature is a good indicator of wound inflammation and infection. Uninfected wounds almost have no temperature difference from the surrounding normal skin but when infected, epidermal temperature increases by 2.46°C. Flexible temperature sensors can provide real-time detection of wound temperature, and allow for early intervention. Pang et al. have developed a smart wound patch with these sensors, which monitored wound temperature and transmitted it to a smartphone device. It was also able to alert the user of abnormal temperature changes in time for adequate treatment.?

Intelligent Treatment?

Intelligent wound healing seeks to promote wound healing by providing an external stimulus to the wound bed, to trigger cell migration, proliferation, and clear infection. ?

Electronic Assistance Healing: When the skin is damaged, an endogenous direct current electric field is naturally generated, which acts on the surrounding cells to actively promote healing. Using this phenomenon, we can supplement the naturally occurring electric field with additional electrical signals that can stimulate the regeneration process of the epidermal wound. This has been implemented in several different ways. One example is by?Long et al., who developed a self-powered electrical-based wound patch to promote wound healing, which used the kinetic energy generated by a rat breathing, and converted it to a discrete alternating current voltage signal through the patch; then, the endogenous electric field is applied on the wound to stimulate skin growth. These electrical signals can also be used to control drug release to a wound bed.?

Intelligent Drug Release: Traditional wound dressings do not allow for a controlled drug release to the wound, which runs the risk of drug resistance within cells. By intelligently regulating the area treated, the flow rate, and the duration of drug release, the outcomes of the wound can be greatly improved with minimal risk. Controlled drug release can be achieved using microfluidic systems that precisely control the flow rate and can be sustained or adjusted as needed. This is especially useful in the treatment of diabetic ulcers, that have a more acidic environment and a higher blood glucose level. These delivery systems can use information from glucose sensors to provide a controlled release of insulin as needed, thereby lowering the blood sugar and allowing normal healing to take place.?Drug release can also be achieved by using thermosensitive wound patches such as N-isopropylacrylamide, which are loaded with the desired drug, and can shrink to squeeze the drug out onto the wound bed when triggered by a temperature increase. These methods prevent excessive use of drugs which can lead to toxic side effects, drug resistance and hinder the healing process.?

Nevertheless, the research of intelligent wound patches faces considerable challenges. On the one hand, the complex manufacturing, difficult integration, and high production cost are the three main obstacles to their application and implementation in healthcare settings. On the other hand, cutaneous wounds are special, such as tissue fluid leaking and sweating caused by exercise that leads to easy falling, causing dissatisfactory sensitivity of detection. By overcoming these challenges, we can then unlock the massive potential that this technology bears and many can reap the benefits of intelligent wound management.?

Sources:

Y. Wang, M. Guo, B. He, and B. Gao, “Intelligent Patches for Wound Management: In Situ Sensing and Treatment,” Analytical Chemistry, vol. 93, no. 11, pp. 4687–4696, Mar. 2021, doi: 10.1021/acs.analchem.0c04956.?

G. Xu et al., “Battery‐Free and Wireless Smart Wound Dressing for Wound Infection Monitoring and Electrically Controlled On‐Demand Drug Delivery,” Advanced Functional Materials, vol. 31, no. 26, p. 2100852, Apr. 2021, doi: 10.1002/adfm.202100852.?