Since ancient times, wounds have been a major doorway to infections, with limited solutions like primitive remedies and magical incantations. Today, the evolution of antibiotic wound treatments has granted the opportunity to prevent potentially fatal outcomes of wounds such as sepsis. In this article, we will start by scratching the surface (pun intended) of primitive wound care and follow up with a deep dive into current and future trends in wound treatment.

A brief history of wound care

Wound care in ancient times

The evolution of wound care is essentially a reflection of human history. Some principles and common ingredients used in wound healing today can be traced back thousands of years. With the expansion of civilisations, wound healing became an essential element to survive during wartime. Many historical records describe wound healing practices in different human cultures, including Egyptian, Greek, Chinese and Sumerian civilisations. Through an empiric approach, people understood that protecting the wound from contamination with proper hygiene and wound dressing is the best way to prevent complications.^1,2 Ancient civilisations commonly implemented complex approaches to wound healing that combined natural, physical and spiritual methods. People who were tasked with caring for wounds were known under different titles. Firstly the swnw (pronounced as ‘sunu’) in Ancient Egypt.³ The conflicting healers of Ancient Greece - on one side being the followers of the father of modern medicine Hippocrates, known as the Hippocrates, while on the other are the Asclepiades who acted on behalf of Asclepius, the Greek god of medicine, the Medicus in Ancient Rome.^4,5 

Several ancient ingredients used for wound healing have proven their benefits and transitioned to modern medical practice:

• Honey - the most common ingredient in wound dressings in ancient civilisations. Honey is a mixture of water, sugars, vitamins, minerals, pigments, and peroxides that give its signature antibacterial, anti-inflammatory, healing and debriding properties. The first written record of honey-containing wound remedies, known as the Edwin Smith Papyrus, dates back to Ancient Egypt around 2500 years B.C.⁶ In modern times manuka honey is one of the most promising wound dressings for nonhealing (chronic) wounds⁷
• Herbs - some of the most widely used herbs for wound treatment include St John’s wort, yarrow, aloe vera, turmeric, and pot marigold, which are used today as well⁸ 
• Minerals - ointments containing zinc, copper, magnesium, and silver salts were used for thousands of years on wounds due to their wound healing and antibacterial effects. Today, mineral creams and ointments are widely used for minor skin injuries such as sunburns, cracked skin, and small cuts

Mediaeval medicine

During the Middle Ages, medical practices started regressing in many areas due to the influence of the Church and the rise of the miasma theory for diseases. More primitive methods based on superstition became common, often leading to more harm than good. That is until the birth of modern surgery in the XVI century.²

The birth of modern surgery

The foundations for modern wound care were set during the XVI century by Ambroise Paré, who documented his work as a military surgeon in his work, “Les Oeuvres”. “Les Oeuvres” describes important insights into the management of wounds, replacing the then brutal methods, such as cauterisation with boiling oil, with more humane treatments based on scientific observations such as dressings with essential oils mixtures. For his groundbreaking contribution to the evolution of wound care, Paré is today considered the father of modern surgery.⁹ Later in the XIX century, the introduction of antiseptics into surgery by Joseph Lister significantly reduced infections in surgical wounds.¹⁰

Current antibiotic wound treatments

For thousands of years, humans have used moulds topically to treat infected wounds without suspecting that they were in fact, setting the ground for what we know about antibiotics today.¹¹ It was not until the XX century when Alexander Fleming made one of the most significant discoveries in medicine - the world’s first identified antibiotic, penicillin. Later, during World War II, researchers started the mass production of penicillin to treat wounded soldiers, thus preventing fatal infections like sepsis.¹² 

Today, many antibiotics are used in wound treatment to prevent further infection. Antibiotics are usually formulated as creams or ointments locally applied to the injured site. Current formulations are generally not based on groundbreaking innovative technologies (read on to find out more about emerging innovations in wound care); instead, they serve a simple but fundamental role in delivering the antibiotic, ensuring that it remains solubilised, stable and effective at the wound site. 

The most widely used antibiotics for topical wound treatment include:

• Bacitracin - a cyclic peptide antibiotic that binds to key metabolic components on the surface of bacterial cells, preventing cell wall formation. Bacitracin is formulated as a zinc salt (bacitracin zinc) since zinc ions facilitate the target binding of bacitracin. Bacitracin is mainly active against Gram-positive bacteria like Staphylococcus aureus, which is the most common cause of skin infections
• Neomycin - an aminoglycoside antibiotic that inhibits protein synthesis in bacterial cells. Neomycin is more active against Gram-negative bacteria like Pseudomonas aeruginosa, the latter being a major cause of severe chronic infections, especially in immunocompromised patients. Neomycin is often co-formulated with bacitracin zinc to expand its antibacterial spectrum
• Polymyxin B - another cyclic peptide antibiotic that, unlike bacitracin, disrupts the structure of bacterial cell membranes and targets primarily Gram-negative bacteria. Polymyxin B is mainly formulated as a mixture of both neomycin and bacitracin
• Fusidic acid is a steroid antibiotic that is thought to inhibit protein synthesis, similar to aminoglycosides. It’s effective mainly against Gram-positive bacteria
• Sulfadiazine - a sulfonamide which acts by inhibiting the metabolism of folic acid, a vitamin which is essential for DNA synthesis and repair. Unlike the previous antibiotics, sulfadiazine has a broad antibacterial spectrum. Sulfadiazine for topical use is formulated as a silver salt (silver sulfadiazine) due to their synergistic action - silver ions disrupt bacterial cell membranes and enhance the antibacterial properties of sulfadiazine.

The future of wound treatment

Nanomedicine in wound treatment

Nanoparticles have been widely used in modern medicine in recent years. Scientists have invented new types of nanoparticles that have the potential to maximise the effects of antibiotic treatments. Nanoparticle-based antibiotic systems are able to increase drug concentration at the desired site of infection and minimise drug concentration in non-infected areas, thus preventing the occurrence of adverse reactions. Homing molecules bound to the surface of nanoparticles can help them target bacteria in a way that specifically prevents the development of antibacterial resistance or biofilm formation.¹³ This means that through nanomedicine, we might be able to create effective antibiotic treatments for nonhealing (chronic) wounds with minimal risk for developing antibiotic resistance.

3D Bioprinting 

An emerging area of modern medicine that produces artificial skin directly onto the wound. This technology uses materials known as bio-inks that are created from a patient’s own cells and grown inside a lab together with other biological compounds such as collagen to create a personalised healthy skin graft for each patient, minimising the risk for graft rejection.¹⁴

DNA Therapy 

Many inherited diseases are associated with wound formation. One such example is epidermolysis bullosa. It is a rare disease that causes skin frailty and blistering in response to mild injuries. Patients are at high risk of life-threatening infections, including sepsis. Vyjuvek (beremagene geperpavec-svdt), recently approved in the US, is the first available topical gene therapy and is indicated for use in patients 6 months or older with dystrophic-type epidermolysis bullosa skin lesions. This treatment uses HSV-1 viral vectors that deliver healthy COL7A1 genes directly to the affected skin sites, which help skin cells to synthesise collagen and promote wound healing, thus restoring the normal skin barrier. Vyjuvek has been shown in clinical trials to increase wound healing in affected patients compared a placebo.¹⁵

Modern Herbal Medicines

Amidst these groundbreaking developments, there is a resurgence of interest in traditional herbal treatments. In contrast to the complex idea of DNA therapy, another recently approved medication Filsuvez uses extracts from birch bark for the local treatment of both dystrophic and junctional type epidermolysis bullosa skin lesions in patients aged 6 months or older.¹⁶ This parallel between two completely different treatment platforms shows that innovation does not exist in isolation of modern technologies but rather builds upon the foundations laid by traditional practices. However, it is important to note that just because a medication is derived from natural sources like plants does not imply that it is safer than “non-natural” medications in any way. The safety profiles of all medications are based on evidence from clinical trial data.

Conclusion

Wound care has significantly transformed over the centuries, from primitive methods to evidence-based treatments. Emerging technologies like targeted antibiotic delivery pave the way for more effective treatment options. One big challenge for wound treatment, especially in chronic wounds, is antibiotic resistance. By integrating complex scientific approaches, we hope to enhance the precision and potency of treatments, preventing resistance and keeping topical antibiotics a reliable option for wound care.