Winning the war on wounds

August 28, 2024 | Dubai, United Arab Emirates

The skin is our first line of defense against a hostile world. The body’s largest organ is remarkably good at keeping out pathogens. It’s also crawling in them. And when accidents happen—or the surgeon’s knife makes an incision—the race is on. Who will win? The wound and its legions of microscopic attackers? Or the body’s natural healing powers and army of defenders? Fortunately, patients have the full weight of medical science in their corner to tip the odds. So, what are the challenges of wound management and how is cutting-edge research and technology revolutionizing how we heal?

Classifying wounds

Wounds can be divided into two categories: acute or chronic.

Acute wounds, such as cuts, bruises, burns, and surgical wounds, occur suddenly and progress through the normal stages of healing, from inflammation to repair.^[1] Chronic wounds, such as pressure ulcers and diabetic ulcers, develop slowly and linger. Acute wounds that fail to heal or heal too slowly are reclassified as chronic wounds.^[2]

All wounds risk cell death and (potentially life-threatening) infections, exacerbated by the rise of antimicrobial resistance. Natural healing is impeded by various common factors, including:^[3]

ischemia (impeded blood flow in and/or out of the affected area)
microvascular damage (e.g. diabetes)
vasoconstriction (e.g. effect of nicotine)
malnutrition
stress
underlying health conditions
a pre-existing infection

Painful reality

Wounds are one of the biggest drains on healthcare.

Most wounds are acute and actually occur in hospitals, owing to the increasing number of surgical procedures. Good technique and suturing are critical; separated wounds can lead to over nine extra days in hospital and almost a 10% higher chance of mortality.^[4]

Chronic wounds, though, are the trickier and more expensive problem – costing the global healthcare system hundreds of billions of dollars every year.^[5]

Aging populations, diabetes, obesity, and lifestyle factors are contributing to a rising incidence of chronic wounds, such as venous leg ulcers, pressure ulcers, and diabetic foot ulcers. In the United States alone, 2% of adults have chronic wounds^[6] and pressure injuries affect up to 2.5 million patients annually, leading to approximately 60,000 deaths each year.^[7]

Diabetic foot ulcers, in particular, pose significant challenges.^[8] Around 25% of diabetic patients face a lifetime risk of developing one or more, with 15% progressing to amputation.^[9] Around 1 in 3 people who develop diabetic foot ulcers die within five years, a higher percentage than breast cancer, prostate cancer, and colon cancer.^[10] To put this crisis into context, there are currently around 400 million people worldwide with diabetes; by 2024, there will be 783 million.^[11]

Diabetic foot ulcers exemplify many of the reasons chronic wounds are challenging to treat. Restricted blood flow slows the body’s ability to heal; nerve damage means wounds often go undetected and patients delay treatment; and the longer wounds take to heal, the more likely infections and serious complications.

The fundamentals of wound healing

Effective wound healing relies on a systematic approach known as wound bed preparation. This process involves assessing the wound, removing barriers to healing such as dead or infected tissue (debridement), maintaining moisture balance, managing bacterial balance, and wound cleaning.^[12] Wounds may then heal naturally, require closure, or potentially skin grafting.

Surgical wound care uses staples, sutures (including absorbable options), and adhesive strips to promote tissue repair and minimize tension.^[13]

Pressure injuries are typically managed with foam dressings and specialized mattresses to alleviate pressure.

Open wound management emphasizes maintaining moisture balance, preventing infection, and addressing underlying conditions like vascular disease, nicotine use, and high blood glucose levels.^[14]

Serial debridements may be necessary to minimize inflammation and infection progression, with severe infections requiring targeted treatments. Absorbent materials like alginate dressings are employed in highly exudative (weeping) wounds. Negative pressure wound therapy (NPWT), whereby suction is applied to the wounds in addition to dressings, aids in moisture control, capillary perfusion, wound contraction, and debris removal.^[15] Low-frequency ultrasound therapy has been used to promote healing by various mechanisms for chronic wounds, such as diabetic ulcers, pressure ulcers, and venous ulcers.^[16]

Open for innovation

Despite an extensive range of established treatments, the science of wound healing is a dynamic field. Innovation is driven by the increasing wound burden, lack of consensus over optimal strategies,^[17] the financial imperative to reduce the cost of treatments, increased awareness among patients and healthcare providers, and the development of new technologies increase demand in turn.^[18] Let’s explore some of the more recent, emerging, and cutting-edge treatments.

Biologics

While most wound care innovations have targeted macroscale healing, there is growing potential to address microscale pathophysiology.^[19] Biologics encompass a broad spectrum of therapeutic agents, ranging from vaccines to monoclonal antibodies and even products derived from human blood and plasma.^[20] They hold immense promise for wound healing, particularly chronic wounds.

Traditionally, commercially available biomaterials have primarily targeted wound symptoms, such as exudation, moisture imbalance, or infection.^[21] However, more advanced biologics are emerging, designed to mimic the biophysical cues that regulate immune responses and resolve inflammation.^[22]

Stem cells can differentiate into various cell types within the body, underpinning numerous therapeutic applications, including accelerating wound healing processes.^[23]

Growth factors are proteins that are pivotal in orchestrating the complex wound-healing process. Recent advances have led to the development of targeted therapies utilizing growth factors to enhance wound healing outcomes, including platelet-derived growth factor (PDGF) and epidermal growth factor (EGF).^[24]

Bioactive dressings incorporate biological components or mimic physiological processes to enhance wound healing. These dressings may contain growth factors, extracellular matrix components, or other bioactive molecules to promote tissue repair and regeneration.

Low-cost bio dressing for healing chronic wounds A team led by a researcher from Michigan State University is developing an affordable biopolymer dressing to aid in healing chronic wounds. Current technologies are often too expensive, limiting their widespread use. The team’s approach involves using readily available biopolymers to keep production costs low. The dressing, made from a framework of nanofibers including collagen, mimics the extracellular matrix, promoting cell migration and new blood vessel growth. It degrades over time, eliminating the need for removal and reducing potential aggravation to the wound. At an estimated cost of US$20 per dressing, it could be accessible to resource-strapped healthcare systems.^{^[25]}

Wound closure and healing

Acute wounds, like surgical and trauma wounds, typically use bandages to absorb exudate, ensure tight wound closure, and control infection. Most recent advances focus on tight wound closure, such as highly adhesive dressings and the incorporation of hydrogels with surgical meshes for added adhesion, flexibility, permeability, and strength.^[26] Advanced anti-scarring and healing-promoting therapies are also in the pipeline.^[27]

For chronic wounds, advanced bandages address dysregulated inflammation, replace skin tissue, and prevent infection.^[28] In diabetic wounds, inducing acute inflammation has shown promise in jump-starting healing.^[29]

New therapies for treating burns, including a treatment derived from enzymes found in pineapple plants, are undergoing clinical trials.^[30]

Emerging treatments

Smart tech. Integrating smart technology in wound care is increasingly popular, offering real-time and remote monitoring of wound healing processes through sensors in smart dressings. Researchers have developed a custom 3D-printed device to deliver charged biomolecules and ions to promote wound repairs. A recent study noted the platform’s flexibility and scalability, showcasing its potential for various therapeutic applications.^[31]

3D-printed stem cells. The proliferation of 3D printers could herald a new era in personalized wound care. A research team at the University of Toronto has unveiled a groundbreaking handheld 3D printer designed to deposit stem cells onto wounds embedded within bioink-based skin grafts to facilitate tissue regeneration.^[32] While initially focused on treating full-thickness burns, the technique holds potential for treating chronic wounds. The simulation of chronic wounds through advanced skin substitutes and organoids, enriched with immune cell components, offers prospects for identifying novel therapeutic targets – aiding diagnosis and paving the way for molecular profiling of wounds. One day, wound dressings equipped with sensing capabilities may even be able to detect and treat individualized wound environments autonomously.^[33]

Collagen-based wound dressing. Skin dressings cannot often form antibacterial barriers while promoting efficient healing. A recent breakthrough in human collagen VI’s healing and antimicrobial properties has spurred the development of a novel bioactive wound dressing by the Swedish company Colzyx.^[34] The product aims to accelerate wound healing while fighting off bacteria. Currently undergoing research and validation, Colzyx has secured US$ 4.3 million in funding, including US$ 3 million from the European Union’s Horizon 2020 research and innovation program.

Bacteria-killing lasers. VulCur Medtech is pioneering a handheld laser device to target and eradicate biofilm-producing bacteria.^[35] The company aims to prevent amputations and unnecessary antibiotic use by eliminating biofilm in chronic wounds. Funding from sources like the Eurostars-2 joint program and the European Union’s Horizon 2020 research and innovation program supports VulCur Medtech’s efforts, including US$ 1.2 million allocated towards regulatory approval costs.

Fluorescence point-of-care imaging. This non-invasive technique enables clinicians to assess bacterial quantity and virulence accurately and customize treatment plans for each patient. In a recent study involving 350 individuals with diabetic foot ulcers, MolecuLight, a handheld portable autofluorescence imaging device, was shown to lead to a 23% increase in the number of healed wounds within 12 weeks.^[36] Additionally, the adoption of fluorescence imaging was linked to a 49% reduction in antimicrobial dressing prescriptions and a 33% decrease in antibiotic prescriptions.

Harnessing the power of plasma

It sounds more like something to inflict wounds in science fiction than to heal them in real life. But incredibly, plasma is already being deployed in the lab and clinical settings to do just that.

Plasma, often called the fourth state of matter, is generated when an electric or electromagnetic field is applied to a gas, ionizing it and giving rise to excited species, photons, and charged particles. Two types of plasma exist: hot (thermal) and cold (non-thermal).

Hot plasma, for obvious reasons, is a non-starter for treating wounds. Cold plasma, however, can safely influence essential biological processes such as cell death, bactericidal action, vasodilation, oxygenation, and angiogenesis. By targeting bacterial DNA, even in antibiotic-resistant strains, and promoting tissue oxygenation and angiogenesis, plasma demonstrates significant potential in treating chronic wounds, particularly super-infected ones.

Initial laboratory tests have demonstrated the effectiveness of plasma in disinfecting various bacterial strains, including antibiotic-resistant ones, offering hope for future clinical applications^[37]. Pilot studies involving patients with severe wounds have shown promising results, with significant tissue improvement observed after plasma treatment. Beyond wound healing, plasma technology holds promise for various biomedical applications, including cancer therapy and drug delivery, because it can increase tissue oxygenation and enhance chemical uptake in cells and tissues.

A team of researchers in Germany has unveiled a pioneering cold plasma technique to accelerate the healing of stubborn open wounds, including ulcers, diabetic complications, and skin ailments like dermatitis and psoriasis.^[38] Developed by Prof Wolfgang Viöl of the Fraunhofer Institute for Surface Engineering and Thin Films, in collaboration with Cinogy and the Department of Dermatology, Venereology, and Allergology at the University Medical Centre Göttingen, the handheld device, comparable in size to a torch, houses an electrode positioned near the wound site. Through the application of high voltage, an electrical field is generated, ionizing the air and enveloping the wound in cold plasma to eradicate surface bacteria while stimulating microcirculation within blood vessels, bolstering oxygenation, and accelerating the healing process. Remarkably, patients report only a mild tickling sensation during treatment. Initial clinical trials indicate superior speed and efficacy compared to existing therapies, such as UV radiation, ozone, and electrotherapy. The compact size and user-friendly design promise widespread adoption, even in home settings.

Precise cutting and faster healing with Plasmajet

Another innovative technology pushing the boundaries with plasma is PlasmaJet, developed by US-based Plasma Surgical, with whom Jameel Health announced a partnership agreement in early 2024. PlasmaJet is a multi-functional surgical tool harnessing plasma technology for precise soft tissue manipulation.

The PlasmaJet system delivers gas and energy from a console to a handpiece to generate pure plasma in a controlled, high-energy, rapidly dissipating stream. The device facilitates various surgical procedures, from cutting and kinetic dissection (utilizing kinetic energy for tissue manipulation) to microlayer vaporization (precise skin layer removal for rejuvenation). It promotes blood coagulation and selective surface sealing of wounds, blood vessels, the gastrointestinal tract, and other organs during surgery to manage bleeding and minimize complications.

“PlasmaJet is a major evolution in surgical innovation,” says Dr Jean Philippe Estrade of Clinique Bouchard Marseille, France, “Plasma energy allows both a frank and precise dissection of the tissues and the possibility of ensuring the patient an ultraconservative treatment.”

The PlasmaJet has already been used to treat over 40,000 patients in more than 20 countries all over the world, in applications ranging from endometriosis to cancer treatments.

Winding up the wounds

From cutting-edge biologics to the transformative potential of plasma, the future of wound healing heralds increased precision, personalization, accessibility and better outcomes – particularly in tackling some of the most challenging, chronic wounds. With continued collaboration between researchers, healthcare providers, and technology developers, we can expect many more exciting innovations to make their way from the lab to the clinic—and even the home—giving millions of patients an overwhelming advantage in the war on wounds.

Said Dr Akram Bouchenaki, Chief Executive Officer of Jameel Health. “Enabling patients to recover from wounds as quickly and effectively as possible is a significant ongoing challenge in healthcare. The body’s natural defenses do an excellent job, but any extra support we can provide through advanced technologies like PlasmaJet has the potential to reduce risks and significantly improve patient outcomes. Our partnership reflects our commitment to collaboration with world-class partners, leading the charge in pioneering new wound healing technologies. Our unwavering focus on inclusivity drives us to accelerate access to affordable modern healthcare, reaching more people in diverse locations and addressing unmet needs across the Global South.”

^[1] https://www.ncbi.nlm.nih.gov/pubmed/32993416

^[2]https://www.rch.org.au/rchcpg/hospital_clinical_guideline_index/Wound_assessment_and_management/

^[3] https://www.science.org/doi/pdf/10.1126/sciadv.ade7007

^[4] https://www.science.org/doi/pdf/10.1126/sciadv.ade7007

^[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031231/

^[6] https://www.liebertpub.com/doi/full/10.1089/wound.2019.0946

^[7] https://www.science.org/doi/pdf/10.1126/sciadv.ade7007

^[8] https://www.who.int/health-topics/diabetes#tab=tab_1

^[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919962/

^[10] https://www.researchgate.net/publication/5693834_Guest_Editorial_are_diabetes-related_wounds_and_amputations_worse_than_cancer

^[11] https://idf.org/about-diabetes/diabetes-facts-figures/

^[12] https://pubmed.ncbi.nlm.nih.gov/32681877/