Key scientific evidence for the presence of biofilm in human wounds.
Since the turn of the millennium, an evolving body of scientific and clinical evidence indicates that biofilm is implicitly linked to delayed wound healing and infection. Currently, wound anti-biofilm strategies rely on non-specific wound bed preparation techniques involving physical debridement and cleansing, and innovative technologies designed to specifically manage biofilm have only just begun to emerge. The first output of anti-biofilm research and product development in wound care show great promise for patients, clinicians and healthcare institutions. The aim of this chapter is to address the current clinical biofilm problem, describe existing and emerging strategies to combat wound biofilm and review the available evidence.
1. Introduction: the clinical problem
Fossil evidence of microorganisms existing as surface-attached microcolonies dates back 3.4 billion years , establishing biofilm as one of the oldest life-forms on earth. The scientific study of surface-attached microorganisms dates back to the seventeenth century , but it is only in recent decades that their relevance has been appreciated in both natural and pathogenic ecosystems [2, 3]. Although the term ‘biofilm’ has been used to describe surface-attached, matrix-encased microbial communities in industrial and environmental applications since the 1930s, it was not until 1985 that Bill Costerton introduced the term into medical microbiology . The importance of biofilm in chronic infections is now widely accepted and there has been an exponential rise in related medical publications since 1975, reaching a number of 3251 in 2013 alone .
The refractory nature of many infections has been largely attributed, in recent decades, to the continuing rise in antibiotic resistance, but the involvement of biofilm in microbial tolerance to antimicrobial agents and immune cells is increasingly recognised. The combined effect of biofilm tolerance and antibiotic resistance are the two most important microbial defence strategies, and in combination present a significant risk to public health. In 1999, Costerton
Any wound that is not healing and that has not followed a normal wound healing trajectory is likely to involve biofilm. Healthy skin is an effective microbial barrier; therefore dermal tissues are intrinsically sterile. However, the surface of the skin is heavily colonised. Damage to or removal of the epidermal barrier layer will inevitably lead to wound contamination and opportunistic microbial colonisation. The innate human immune system can usually counter this invasion but, if the initial contamination event is overwhelming (such as a severe traumatic wound), or contamination is repetitive (for example for a faecally incontinent subject suffering from a sacral pressure ulcer), or if the casualty has a weakened immune system (as a result of age, disease, malnutrition, obesity, smoking, etc.) then biofilm may become established.
The earliest indirect indication of wound bacteria existing in biofilm form involved the detection of extracellular polysaccharide capsules surrounding the cells of both aerobic and anaerobic wound pathogens, using light and scanning electron microscopy . Capsule production is a key component of a biofilm mode of life that can protect bacterial communities from the host immune system . The earliest scientific research into wound biofilm was reported by Serralta
The development and evolution of wound biofilm from contamination to a pathogenic state was proposed in 2004, and the point at which an evolving biofilm begins to interfere with wound healing and increase the risk of infection has largely replaced the previously-used term ‘critical colonisation’ . In 2008, a hypothesis (that was considered novel at the time) relating to why chronic wounds fail to heal was reported . Based on their previous experiences with chronic
Since the turn of the millennium, wound biofilm has been proposed, investigated and confirmed, as a factor in chronic wound pathogenesis. From initial evidence of their existence , role in wound healing , and the simultaneous and pioneering confirmation of their clinical existence in 2008 [10, 11], a large body of scientific and clinical evidence now suggests that biofilm is inextricably linked to wound infection and delayed healing [7, 22–37] (Table 2).
|Chronic (mixed)||50||Light microscopy, scanning
electron microscopy (SEM)
|30 chronic wounds observed to
contain biofilm (60%)
|Chronic (mixed)||22||Confocal laser scanning
|13 chronic wounds observed to
contain biofilm (59%)
|Chronic (mixed)||9||Fluorescence microscopy, CLSM||
|Chronic (mixed)||10||Fluorescence microscopy, CLSM||
|Chronic||1||Fluorescence microscopy||Both samples contained biofilm||9|
|Mixed aetiologies||15||Fluorescence microscopy||7 wounds observed to contain biofilm (47%)||14|
|11||Light & transmission electron
|Only ulcerated and escharotomy
sites contained biofilm
|Diabetic foot ulcers (DFU)||2||CLSM||Both samples contained biofilm||16|
|Acute||16||Light microscopy, SEM||1 acute wound contained biofilm (6%)||10|
|DFU||4||Light & fluorescence microscopy,
|Microcolonies associated with biofilm
observed in all wounds
|Surgical sternal||6||Light & fluorescence microscopy,
|3D biofilm aggregates observed in all
6 infected wounds
|Venous leg ulcers (VLU)||45||Transmission electron
|Biofilm matrices of polysaccharides,
proteins & DNA observed
|Malignant||32||Fluorescence microscopy||Biofilm observed in 35% of wounds||20|
|113||Biofilm-forming capacity of
isolates by culture & SEM
|Significantly more biofilm formed by
wound isolates than others
|Porcine acute||Challenge with antimicrobial agents confirmed the recalcitrance of
|Porcine acute||Polymorphonucleocytes observed on the surface of, but not
||Interactions between MRSA and
healing due to suppression of epithelialisation and expression of
|Murine burn||Microscopic biofilm observed that was not readily removed by rinsing with saline||24|
|Biofilm-colonised wounds highly inflamed; 8 weeks for biofilm-colonised
wounds to heal, 4 weeks for controls
|Biofilm significantly delayed wound healing, even in diabetic mice treated
|Biofilm highly-tolerant to antibiotics & sodium hypochlorite once
established over several days
|Polymicrobial biofilm maintained for 12 days, & delayed healing
|Murine splinted||Biofilms significantly delayed epithelialisation; inhibition of biofilm
restored normal healing
|Rabbit ear||Biofilm and active infection significantly delayed healing; biofilm-
colonised wounds expressed significantly lower levels of
inflammatory cytokines than infected wounds
|Rabbit ear||Biofilm significantly delayed healing; debridement, lavage and silver
sulphadiazine in combination were more effective at
restoring healing than individual treatments
measured by healing inhibition and inflammation; extracellular polymeric substances (EPS)-deficient
did not delay healing
|Rabbit ear||2-species biofilm elicited significantly elevated inflammatory
response & impaired epithelialisation & granulation tissue
formation compared to single-species
|Rabbit ear||Dressing designed specifically to manage biofilm gave significant
reductions in biofilm count & significantly improved wound
healing (granulation & epithelialisation)
|Biofilm developed over time in chronic wounds (similar to humans);
reducing oxidative stress increased their susceptibility to
antibiotics & dismantled biofilm
|Rabbit ear||Wounds showed increased inflammation and delayed healing
|Porcine burn||Biofilm-infected wounds, tolerant to silver dressings, eventually closed, but
skin barrier function compromised
|Diabetic mouse||Diabetic wounds had significantly more biofilm & less neutrophil
activity, thus poorer healing than wild type
In our laboratory, we have used microscopy techniques to better understand the structure and development of wound biofilm. Planktonic cultures of
Scientific, clinical and animal evidence strongly suggests that biofilm delays wound healing , and efforts are underway to understand and develop ways to visualise and control biofilm to aid clinical practice [44, 46]. It has been shown that by targeting and suppressing biofilm healing can be improved, so the onus is now on wound care product developers and manufacturers to offer technologies with anti-biofilm effectiveness.
2. Therapeutic anti-biofilm strategies
With only relatively recent recognition of the existence of biofilm in wounds and consequent role it plays in delayed healing and chronicity [8, 10, 11], the development of effective therapeutic treatments and strategies to date has been very limited. However, this late recognition does mean that wound care researchers can benefit from the knowledge gained in other industries and in related healthcare areas such as dentistry and indwelling medical devices. Here treatment strategy options are well developed and broadly similar. Although the intention to prevent, remove and kill bacterial biofilm is the same, there is a significant challenge in selecting wound treatments that have an appropriate balance of safety versus efficacy. There are also challenges in simultaneously addressing the other clinical needs of the wound as, unlike inert medical devices or tooth enamel, the surface of a wound, particularly a chronic wound, can be acutely sensitive and fragile.
Wound biofilm is generally initially attached to the wound bed which is a dynamic mixture of viable and non-viable (slough) tissues. Exudate permeates through this underlying tissue providing moisture and nutrients to developing biofilm. Treatment and prevention of wound infection usually consists of systemic antibiotics and/or topical antiseptics. The polymicrobial nature of wound bioburden  and difficulty in identification of species present means that antibiotic selection and coverage is imperfect. Chronic wounds are often poorly perfused with blood (a causative factor) therefore delivery of systemic antibiotics, at a sustained therapeutic concentration, for the period necessary to diffuse into a biofilm and take effect, is an additional challenge . Topical antiseptics are preferred because of their broad spectrum of activity, but they suffer from a lack of selectivity towards bacteria and therefore can be toxic to host tissues. General reaction with organic matter and continual dilution and removal with wound exudate mean that an antimicrobial product needs to be continuously instilled  or formulated for slow release and physical retention within the wound or dosed at high concentration. Clinical evidence suggests that none of the above existing systemic or topical treatments are particularly effective against wound biofilm. Therefore, different strategies are required.
It is convenient to consider these strategies in broad groups aligned with the clinical intent as mentioned above—to prevent, to remove, to kill biofilm-associated organisms (Figure 2)—and many treatments will involve combinations of these with the best being a combination of all three. We will also discuss the anti-biofilm effectiveness of existing methods together with associated devices, and how some of these are providing therapeutic advances in the emerging ‘biofilm era’ of wound care.
2.1. Prevention of biofilm
Microbial contamination of breaches in skin integrity is inevitable, unless the wound is created under aseptic surgical conditions, and wounds that are not successfully managed can become chronic and at risk of infection. The ideal situation is to prevent bacteria entering the wound in the first instance. The risk of wound contamination post-surgery can be addressed by applying effective microbial barrier dressings. In the 1990s
Although barrier dressings have an important role to play in minimising infection, it is most likely that any open wound will become contaminated to some extent (chronic wounds will become significantly more contaminated than most surgical wounds). Consequently, an important infection control strategy at this point is to prevent microbial attachment to the wound tissue. This might be achieved by chemical or biological treatment of the wound surface. Examples of the former are lactoferrin and xylitol. Lactoferrin [52, 53] is a protein that is believed to inhibit the effectiveness of bacterial adhesins by its ability to sequester iron from acidic environments, particularly for Gram-negative bacteria . It has proven useful in the preservation of meat but in a living system with a functioning circulating system supplying an excess of iron and buffering to neutral pH there will be challenges in maintaining efficacy. If derived from non-human sources there is also the possibility that lactoferrin may be identified by the immune system as a threat and illicit an inflammatory response. Xylitol is a naturally occurring sugar that binds to the surface of Gram-positive bacteria preventing adhesion , inhibiting glycocalyces (exopolymeric substances) and disrupting cell wall growth . But xylitol faces the same challenge as lactoferrin in that it is a freely soluble substance and will be difficult to maintain at an effective concentration in an exuding wound. Gallium is also mooted in this space as Ga3+ is similar to Fe3+ in size but does not undergo the same redox reactions (Fe3+ Fe2+) and therefore interferes with bacterial attachment and proliferation .
If microorganisms gain the opportunity to attach to wound tissue and acclimatise to the environment, then subsequent colonisation will lead to the development and maturation of a predominantly biofilm population that is protected from the immediate hostilities within the wound environment (Figure 1). Two potential biological approaches for controlling biofilm development are quorum sensing (QS) inhibitors and probiotics. Quorum sensing is an active field of research with over 100 bacterial species identified as having the ability to communicate by release of small signalling molecules . At a critical concentration, microbial communication between cells triggers a change in gene expression which results in a change in behaviour. QS is involved at all stages in the biofilm life cycle (initial attachment, EPS expression, proliferation, maturation and dispersal) and is implicated in biofilm virulence. In practical terms, this minimum concentration dependence translates into a minimum threshold bacterial population density. However, it must be borne in mind that wound biofilms are polymicrobial [56–58] and although approximately 50% of all known QS bacterial species have the ‘universal’ autoinducer 2 (AI-2) , QS signal molecules vary between species and strains. Therefore, a universal inhibitor for wound biofilm formation seems unlikely in the near future. Probiotics [59, 60] offer the interesting possibility of prophylactically colonising the wound with non-pathogenic bacteria.
Finally, often overlooked is the management of the wound environment itself—establishing the best conditions in which the body’s immune system can function and/or creating conditions which reduce bacterial proliferation and biofilm development. The optimal moisture balance in the wound bed is reported to be 100% humidity with no free liquid , and it has recently been suggested that poor exudate control is likely to encourage the development of biofilm . Chronic, non-healing wounds are often characterised by a high pH (7.15–8.9) and healing wounds tend to have a lower pH . The increased production of
2.2. Removal of biofilm
By the time wounds are presented to a wound care specialist, the majority of non-healing traumatic and chronic wounds are likely to be biofilm impeded. There is a long history of removing non-viable and necrotic host tissue from wounds (debridement) in order to encourage the inflammatory, granulation and epithelialisation processes of wound closure. Surgical debridement techniques can range from aggressive surgical or sharp removal of tissue to less invasive techniques such as curettage and lavage. This practice is likely to have coincidentally been removing biofilm with beneficial effect. With increasing familiarity with the appearance of biofilm or more likely, the symptomatic signs of its presence, clinicians are seeking methods to physically remove biofilm from wounds. In recent years, debridement devices utilising a number of very different technologies have emerged.
Sharp debridement is the most radical approach and requires expertise . Excision of devitalised host tissue (i.e. necrosis) or infected/biofilm tissue via scalpel or other surgical instrument until the exposed tissue is bleeding would certainly be expected to remove a majority of any biofilm residing in the wound, but the deleterious effects on healing tissues need to be balanced with the need to remove unhealthy tissue. However, sharp debridement has proven successful and advocates such as Wolcott have developed protocols where regular sharp debridement has provided a ‘healing window’ during which improved effectiveness of concurrent antimicrobial treatment has been observed . Hurlow has also reported the atraumatic removal of biofilm above a non-healing surgical wound with exposed tendon using curettage and antimicrobial cleansers [69, 70] (Table 3).
A number of other devices that can be used for wound debridement are now commercially available. Examples include devices that emit energy in the form of water jets (lavage), ultrasound and cold plasma (Table 3). High pressure lavage using hand-held devices  has been assessed in several laboratory and clinical investigations, and there is evidence that removal of unwanted tissue (which may include biofilm) using this method encourages wound progression . Ultrasonic wound debridement has proven effective in clinical cases , and scientific studies support the ability of ultrasound to disrupt biofilm and encourage healing
Unfortunately, in many clinical institutions the skills, training and equipment for the use of advanced debridement techniques or devices may not be available. Under these circumstances simple cleansing, enhanced with ‘soft debridement’ using engineered textiles, may be helpful. Recently, debridement pads or wipes have emerged which aim to gently brush and lift away wound debris. A polyester filament pad has generated encouraging clinical effectiveness data [75, 76] and cost-saving estimates . In addition to disrupting and lifting surface-associated wound debris (which is likely to include biofilm), these soft debridement devices are simple and safe to use, gentle on patients and relatively low-cost, compared to most other debridement techniques and devices discussed in Table 3.
More thorough biofilm removal may be achieved by degrading the structure of the EPS such that it flows away from the wound or can be more readily irrigated or absorbed by absorbent dressings. General proteolytic enzymes have been used for many decades to remove slough and necrotic tissue, but, as EPS is not primarily comprised of extracellular proteins for its structural integrity, these are ineffective. This fact has been utilised by an aid to detect the presence of wound biofilm . Alternative enzymatic candidates that are effective against polysaccharides have been identified and reviewed [78, 79], and include: α-amylase (mammalian), polysaccharide depolymerase (bacteriophage), alginate lyase (bacterial) and glycoside hydrolase (DspB) (bacterial). Generally, the kinetics of enzyme reactions are known to be sensitive to pH, for example Dispersin B, despite demonstrating some activity
|Curettage||(Clinical) Gentle scraping of suspected biofilm (in combination with other antimicrobials) improved healing in case studies||69,70|
|Lavage/water jets||(Clinical) Indirect anti-biofilm evidence; debridement with
|(Clinical) Indirect anti-biofilm evidence; case study evidence that
|Soft debridement pads||(Clinical) Indirect anti-biofilm evidence in case studies where sloughy wounds were well managed using
|(Clinical) Debridement was classed as effective in 94% of patients, removing debris and slough, in a 57-patient study using
Structural degradation of biofilm EPS can also be achieved chemically. Divalent cations such as calcium and magnesium are known to be involved in cross-linking polysaccharides within EPS and manganese and iron are involved in bacterial metabolism and cell wall structure . Competition for these ions or their removal (chelation) will therefore affect biofilm formation and strength. Metal chelating agents are a diverse set of compounds but biocompatibility and safety considerations restrict those that can be considered for wound care to ethylenediamine tetra acetic acid (EDTA) and its homologues and polyanionic compounds such as phosphates and citrate. The most widely discussed of these as an anti-biofilm agent and the one with the greatest affinity for calcium and magnesium cations is EDTA. The literature primarily focuses on the tetra-sodium salt form but only at high pH (>pH 10) , which is incompatible with wound management practices. Lower pH forms of EDTA, such as the di-sodium salt, are effective but all anionic chelating agents are pH-sensitive. A water-soluble gel formulation that contains 0.1% EDTA, acetic acid, citric acid and carbopol has demonstrated anti-biofilm effectiveness against
Empirical experience in other industries such as food, laundry, personal washing and dental products  has shown the utility of surfactants as anti-biofilm agents to facilitate penetration of combination agents through biofilm EPS , leading to detachment from surfaces and prevention from re-deposition by micelle formation. An anti-biofilm gel comprising a surfactant and calcium chelator has shown
2.3. Killing of biofilm microorganisms
The efficacy of existing antimicrobial therapies in wound care has almost exclusively been based on their activity against susceptible planktonic bacteria. Whilst associated devices may be useful in controlling this bacterial phenotype by reducing the risk of contamination and dispersal, their effectiveness against biofilm is unproven. Indeed, the prevalence and recurrence of chronic wounds suggests that most antimicrobial therapies are ineffective.
Considering the selective and specific action of antibiotics, the polymicrobial nature of wound bioburden and the increasing threat of multi-drug resistant organisms (MDROs), the effectiveness of antibiotics in chronic wound care is questionable. However, utilising state of the art molecular microbiological techniques, personalised cocktails of topically-applied antibiotics yielded better results than patients receiving systemic antibiotics prescribed using the same diagnostic techniques who, in turn, yielded better outcomes than a standard-of-care group treated upon data from standard culture techniques . Unfortunately, this level of diagnostic sophistication is not within the reach of most health care systems, and therefore we must await further technological advancements so that it becomes generally affordable.
The majority of wound treatments do not have the benefit of sophisticated microbiological analysis; therefore any antimicrobial therapy administered must have broad-spectrum activity. Choice then becomes restricted to antiseptics which can only be applied topically. Antiseptics are chemically reactive species that are largely non-selective in their action, therefore potential cytotoxicity (local toxicity to skin cells) and systemic toxicity must be taken into account. Toxicity is generally managed by limiting the concentration and time of exposure to the antimicrobial agent. Therefore, antimicrobial cleansing at dressing change may involve slightly higher concentrations of antiseptic than an antimicrobial dressing which may stay
Clinical experience and safety reviews have limited the number of usable antiseptic substances. Currently, silver is the most widely-used topical antiseptic agent, primarily due to its good safety versus efficacy balance . Silver is the most studied topical antiseptic [52, 53], and ionic silver—the antimicrobial active form—has a particularly high affinity for sulphur atoms, binding irreversibly to thiol groups. Ionic silver also binds to nitrogen atoms in amines and oxygen atoms in carboxylates, although less strongly. These three interactions lead to very efficient denaturing of peptides, proteins and enzymes—all of which are essential to bacterial structure and metabolism. However, carboxylate functional groups are also found within the polysaccharide in EPS. Therefore, although ionic silver may be inactivated by EPS and other organic matter within the biofilm, there is a theoretical basis for it to have some biofilm disruptive effects. Evidence for this effect was a reduction in EPS mechanical strength of an
Molecular iodine has proven too toxic for direct application but, by complexation with a carrier molecule and careful formulation, acceptable slow release products have been developed. Although the mode of action of molecular iodine is not fully understood , studies suggest that in common with silver, sulphur atoms are a reaction target resulting in protein denaturing and subsequent changes to cell wall structure . Iodine will react with unsaturated fats and lipids and organic matter within the wound, and is known to be trapped by polysaccharides. There is limited evidence that molecular iodine has anti-biofilm properties, aside from in simple
Evidence for the anti-biofilm effects of the cationic, nitrogen containing, surfactant-like antibacterials—chlorhexidine (CHG), PHMB and octenidine—in wound care is limited. CHG has been shown to have limited effect against some biofilms
The next most popular traditional antiseptic substances are the molecular halogens and related oxidising compounds. Chlorine itself is too toxic to be used and hypochlorite-based bleaches are considered too cytotoxic for general wound care. Hypochlorous acid (HOCl) and chlorine dioxide (ClO2) are under consideration  as potent, fast-acting cleansing solutions, and some early anti-biofilm effectiveness has been observed
EPS mechanical strength after application of dilute (50 ppb [ng/ml])
range of biofilm models
least 7 days, independent of the microbial strain
demonstrated greater anti-biofilm activity than silver dressings
demonstrated anti-biofilm activity in
releasing bacteria for killing, by
significantly more effective than inactive controls in porcine dermal wounds
|(Clinical) Signs of biofilm & infection reduced, healing
progression observed in 124-patient study using
biofilm by live-dead staining with confocal microscopy
disrupted, releasing bacteria for killing, using a concentrated HOCl solution
|(Clinical) Signs of infection reduced & progress toward
healing in a 31-patient study using
|(Clinical) Infection contolled & wounds healed in
14 osteomyelitis patients using
2.4. State of the art today
2.4.1. Multi-modal strategies
Perhaps the most straightforward way for wound care clinicians to implement more effective biofilm management strategies today is to consider how dental care has embraced multiple strategies to manage dental plaque biofilm. By using combinations of debridement (brushing, flossing), surfactants with antimicrobials (toothpaste), and antimicrobial rinses (mouthwash), most consumers manage biofilm effectively on a daily basis to maintain oral hygiene, and prevent conditions such as dental caries and periodontitis.
Biofilm-based wound care (BBWC) is an emerging and evidently effective way of combining multiple modes of wound treatment to improve the health of chronic and infected wounds [68, 85, 109]. Practised initially by the pioneering wound care physician, Randall Wolcott in Texas, a first assumption of BBWC is made that most (if not all) chronic or infected wounds contain biofilm. A further assumption is that one mode of treatment may not suffice, therefore the use of combinations of vigorous debridement, cleansers or gels, topical antimicrobial or anti-biofilm agents, and wound dressings, is required. Wolcott
We also firmly believe that the multi-modal approach is the most effective way of rapidly improving wound health in chronic wounds that are likely compromised by biofilm or infection. A key component in such protocols of care is undoubtedly efficacious wound dressings which can provide effective, sustained and safe antimicrobial and anti-biofilm action. Although the focus here is on therapeutic approaches towards wound biofilm, biofilm cannot be considered in isolation. Other challenging wound conditions must be considered alongside biofilm—exudate must be managed, infection must be controlled, the wound must be protected, and pain must be considered—to provide outcomes that can improve quality of life.
Most established antimicrobial dressings are very efficient at managing planktonic bacteria, thereby limiting initial contamination and spread of infection. However, they all suffer the same challenge in the treatment of biofilm in that the antimicrobial agent must penetrate the EPS in order to reach the target bacteria and, when they do so, they largely rely on metabolism to draw them into the bacterial cell for them to act. EPS can restrict the movement of antimicrobial agents by binding them and increasing the likelihood of reaction with other organic matter. If the agent is able to reach the target bacterial cell it must do so in a concentration sufficient to be cidal for the sessile (biofilm) phenotype. Therefore, it is clear that universally successful antimicrobial therapy using a topical antiseptic agent can only be achieved by a sustained application or release in combination with some form of EPS (biofilm) disruption.
2.4.2. An anti-biofilm wound dressing
In 2009, the authors of this chapter undertook a substantial research project to design a wound dressing specifically to manage biofilm. The starting point was taken as an existing antimicrobial dressing,
In the laboratory
The efficacy of this combination of ionic silver, metal chelator and surfactant has also been demonstrated in an FDA-recognised
Most encouraging is the early clinical performance data emerging for this new anti-biofilm technology. Harding
|Assessed quantitatively by viable counts & confocal scanning laser microscopy,
|Dressing & silver nitrate+EDTA+BC eradicated
|The new dressing technology gave 2 log10 reductions in
|Clinical study||An acceptable safety profile was demonstrated; after 4 weeks of the new dressing then 4 weeks CMC 12% of wounds healed, 76% showed improvement; mean ulcer size reduction 55%; subset of 10 infected wounds reduced in area by 70%||126|
|Clinical evaluation||The new dressing resulted in an average wound closure of 73% after average of 4.1 weeks of use in 113 cases; 17% of wounds healed completely||127|
|62% average wound closure after 5.4 weeks of
|Safety & effectiveness demonstrated in 112-case evaluation; suspected biofilm coverage of wound reduced; 13 of wounds healed completely, 65% improved after 3.9 weeks of
3. Conclusions and future perspectives
Biofilm is increasingly accepted as an integral component of wound recalcitrance and infection, and is likely a key reason for the frequent failure of antibiotics and antiseptics in wound healing. Strategies for combating wound biofilm are currently limited and non-specific physical debridement techniques—from physical removal with absorbent dressings, pads and wipes, to sharp and surgical tissue removal—remain the most effective approach. Despite the limited available anti-biofilm wound strategies, efforts are in progress to develop durable medical devices and wound dressings that combine anti-biofilm and antimicrobial activity. To-date and to our knowledge, only one dressing has been designed to combat biofilm (Figure 3), and there is a growing body of evidence demonstrating the exceptional clinical effectiveness of this dressing (
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