The invisible barrier to healing

Some injuries, such as diabetic foot ulcers , venous leg ulcers, pressure ulcers and some surgical wounds, can be particularly susceptible to delayed healing.¹

By definition, chronic (or hard-to-heal) wounds have a slow healing rate and, despite of standard therapy, they fail to reduce in size by 40%-50% within 4 weeks² and/or persist for more than 12 weeks.³
Without proper treatment and management, wounds can persist for months or even years, increasing the risk of infection and amputation.⁴

Chronic wounds tend to recur in over 50% of cases, leading to functional impairment, local and/or systemic complications, and decreased quality of life.³
One of the main reasons why wounds are so difficult to heal is related to the presence of biofilms, which affect all phases of wound healing and are considered to be independent factors in delaying normal wound healing.⁵

Biofilms are complex communities, consisting of different bacterial populations and fungi encased in a protective matrix of extracellular polymeric substance (EPS).⁶

This matrix helps them to adhere to the wound bed, protects against environmental stresses, antimicrobial agents and the host immune system, while allowing movement of nutrients and messenger molecules resulting in different behaviours, such as becoming resistant to certain antibiotics, aggregate more to form thicker biofilm and enhance movement to spread infection.^5,8

Bacteria can exist in at least two growth forms:⁹

• Planktonic: Single, fast-growing cells that move freely in their environment
• Aggregated communities: Attached to solid surfaces or to each other, slow-growing cells that can lead to biofilm formation.

Each state has a role to play in delaying healing and causing infections of both acute and chronic wounds. However, the virulent biofilm state is the fundamental reason that wounds do not heal in a timely manner.¹⁰

1. Individual planktonic bacteria attach to the wound surface

2. The bacteria colonise the wound surface and form a colony (biofilm)

3. The biofilm increases in size and triggers subclinical signs of infection in the host

4. The biofilm has matured

Biofilm is present in most chronic wounds and evidence suggests it plays a greater role within acute wounds than previously considered.^11-12

In chronic (hard-to-heal) wounds, studies identified the presence of biofilms in 60% to 100% of samples.⁹

Biofilms pose a significant clinical challenge, as wounds that contain them may not be identified, resulting in ineffective treatment and delayed healing.^9,12,13 In fact, the presence of biofilm in wounds cannot be determined solely by visible changes, as many seemingly healthy wounds actually contain biofilm.¹²

As a result, the presence of microbial biofilms may go unnoticed during the diagnosis and treatment phase and can lead to misdiagnosis and severe health consequences, including resistance and increased tolerance to most-used antibiotics, persistent diseases favouring biofilm extension, and modification or failure of the host immune system.^5,8,13

The biofilm on the wound surface can be removed by mechanical debridement, but the remaining free bacteria are able to rapidly reestablish the biofilm with increased resistance to antimicrobial agents within 24 hours, which makes it more difficult to remove.¹⁵

Treatment approaches for biofilms in hard-to-heal wounds have relied heavily on the use of conventional antibiotics and antimicrobials. These include widely used topical antibiotics and antiseptics and systemic antibiotics, including broad spectrum agents. However, biofilms often respond poorly to antibiotic regimens, rendering their extensive use ineffective and even indiscriminate and unnecessary, also given the risk of emergence of antibiotic-resistant strains.¹⁷

Microorganisms tend to develop phenotypes of tolerance and resistance to antimicrobials and to the host’s immune defence mechanisms, and systemic antimicrobial therapy is usually not recommended in the treatment of chronic wound infections. On the other side, topical antimicrobials may also fail to achieve bacterial eradication or to prevent recolonisation, due to the low penetrance within biofilms or due to the pharmacokinetics and pharmacodynamics of the substances used.³

Understanding the role of biofilms in impairing wound healing and increasing the risk of infection can lead to tailored antimicrobial strategies, reducing ineffective antibiotic prescriptions that contribute to promoting the emergence of resistant bacteria, decreasing patient quality of life, and potentially adding to healthcare burdens.

The revised wound infection continuum recognises the advancing knowledge on biofilm in chronic wounds and its relationship to both microbial action and clinical signs and symptoms.¹⁸

Wound hygiene  is an anti-biofilm protocol of care designed to overcome the barriers to healing often caused by the presence of biofilm. The core principle of wound hygiene is to remove or minimise all unwanted materials, including biofilm, from the wound, address any residual biofilm, and prevent its reformation to kickstart healing.¹⁹

Repeated mechanical debridement alone is unlikely to prevent biofilm regrowth and early intervention with antiseptics is crucial to suppress reformation. Given the increasing prevalence of antibiotic-resistant bacteria, treatment with systemic antibiotics is less effective today, highlighting the need for antimicrobial, antibiofilm topical agents that do not foster resistance.^11,20