The skin is our most important external defence system, protecting our internal body structures from attack by microorganisms and the harmful effects of the external environment. It’s therefore fitting that if injuries occur to the skin, it can regenerate itself over time. But wound healing is a complex and tightly regulated physiological process that involves the activation of different cell types, and any impairment of the correct sequence of healing processes (homeostasis, inflammation, proliferation and tissue remodelling) can lead to chronic wounds that affect the patient’s quality of life and the care given to them in the clinic.

Wounds are considered acute if the injured tissue requires a healing time of eight to 12 weeks, for example with burns, chemical injuries or lacerations. Meanwhile, chronic wounds are a result of diseases, such as venous or arterial vascular insufficiency, pressure necrosis, cancer and diabetes. The most common chronic wounds seen in the clinic tend to be diabetic foot ulcers and venous leg ulcers. Depending on their cause, chronic wounds can require a matter of weeks, months or even years to heal. They often do not reach a normal healthy state but remain in a pathological state of inflammation. This impaired and delayed wound healing places a significant socioeconomic burden on health systems worldwide, as both treatment and waste costs are tremendous. In the US alone, chronic wounds cost the health care system $25bn annually.

Clinicians and specialised nurses working in wound care are not without tools to help the body repair damaged skin tissue. A plethora of advanced dressings are available that contain ingredients like honey and silver to reduce the bacterial burden and promote the healing pathways necessary for regeneration. But these existing wound dressings are not able to provide dynamic information about the condition of the wound, and it’s for this reason that patients need to be continuously monitored so the care pathway can be altered quickly to respond to changing wound pathologies. This represents a significant financial and time burden, hence it’s why there is an urgent need for devices, dressings and bandages that can provide detailed and quantitative information about a patient’s wound status and allow nurses to manage medication administration remotely. So, what’s required to make this possible? Firstly, sensors are needed that can measure various wound markers, such as pH, wound moisture, oxygen content at the wound site, glucose, temperature and the mechanical and electrical properties of the wound environment.

Active drug delivery

In the most advanced use case of remote management, such sensors would monitor the status of the wound in real time and respond to changes in wound pH, temperature and enzyme level to actively deliver the right therapeutics, for example antibiotics. To achieve automated drug delivery, a smart dressing of this kind requires a reservoir for drugs and drug transport systems, as well as micropumps with microcontrollers that can interact wirelessly with the smartphone or tablet. Active drug delivery methods involve the use of various techniques to facilitate the controlled release of drugs into the body. These methods offer advantages in terms of targeted delivery, enhanced efficacy and improved patient outcomes.

“Mechanical or piezoelectric forces administer drugs at a controlled rate and are designed to provide precise dosing that can be integrated into wearable devices or implantable systems.”

One approach for active drug delivery is through mechanical and piezoelectric pumps. These pumps utilise mechanical or piezoelectric forces to administer drugs at a controlled rate and are designed to provide precise dosing that can be integrated into wearable devices or implantable systems. Thermally actuating thermo-responsive systems are another method for active drug delivery. These systems employ a thermoresponsive material that releases the drug when heated by an external heater, which ensures safe drug delivery. In some cases, localised heating has also been shown to promote fast wound healing as the increase in skin temperature can enhance the permeability of the skin, facilitating better drug penetration.

What can we measure?

Ionophoretic transport is a technique that involves the movement of ions across the membrane. It is achieved by applying an external electrical potential difference, which enhances the transfer of charged molecules or drug carriers to enable efficient drug delivery. Another method is through minimal invasive active jet injection, also known as microneedling. This technique involves the use of a high-velocity jet to create pores in the skin, facilitating the transdermal transfer of molecules. While it has shown promise in drug delivery, the implementation of bulky microneedling systems might be challenging to integrate in a wearable drug delivery system. However, these active drug delivery methods offer exciting possibilities for targeted and controlled drug administration with minimised side effects.

“Minimal invasive active jet injection or microneedling involves the use of a high-velocity jet to create pores in the skin, facilitating the transdermal transfer of molecules.”

Such a smart system was developed by researchers from the University of Nebraska-Lincoln. The group designed a programmable smart bandage that utilised hollow 3D-printed miniaturised needle arrays (MNAs), roughly 2mm in length, to bypass the wound crust and the necrotic tissue to actively deliver drugs to the deeper layer of the wound. For active drug delivery, two miniaturised peristaltic pumps that could manipulate minute amounts of two different drugs with independent dosages were used. Microchannels were fabricated in a polydimethylsiloxane (PDMS) layer with a thickness of roughly 1.5mm. PDMS was used as it is flexible, has a low protein adsorption, a high biocompatibility and a good oxygen permeability.

These microchannels were used to connect the micropump with the MNAs. To keep the whole system flexible and cost efficient, it was designed with two modules; a disposable module with the MNA islands and microchannel arrays; and a reusable module that housed the drug reservoirs, micropumps, power source and electrical circuitry. These two modules were connected by two flexible silicon tubes. The whole platform can be connected to smartphones via Bluetooth and programmed with an app to precisely control the flow rate. The minimum threshold of the pumps was determined to be 0.5V, which resulted in a flow rate of 43.6 ­ μL min −1. In a recent study, the platform was tested using vascular endothelial growth factor (VEGF) delivery through MNAs on diabetic mice with wounds. The MNA-based VEGF group showed 95% wound closure, while the no treatment and topical VEGF groups had 40% and 50% closure, respectively.

A smarter future

The use of sensors for wound monitoring does come with some disadvantages, including issues related to marker specificity; flexibility and the longevity of sensors; their durability in moist and protein-rich wound environments; biofilm formation; and the need for reliable data management networks. Nevertheless, after further research and development, smart dressings may be a promising approach to improve wound management for chronic wounds, and in the process make it more cost-effective. The use of MNAbased patches for wound care might be an effective paradigm shift from the current methods that will be used in clinical wound care practices.

Smart patches is an exciting field that combines various disciplines such as wearables, medical technology and sensor technology. Optimised wound care can be a game changer for hospitals and care facilities as it enables resources such as time and material to be saved. For this reason, the topic will also be discussed within the framework of the IVAM focus group on flexible and hybrid electronics as well as the focus group on medical technology in the coming years. ­