HARD-TO-HEAL WOUNDS
Hard-to-heal wounds, biofilm and wound
healing: an intricate interrelationship
ABSTRACT
Hard-to-heal wounds are a major public health problem that incur
high economic costs. A major source of morbidity, they can have an
overwhelming impact on patients, caregivers and society. In contrast
to acute wound healing, which follows an ‘orderly and timely reparative
process’, the healing of hard-to-heal wounds is delayed because the usual
biological progression is interrupted. This article discusses hard-to-heal
wounds, the impact they have on patients and healthcare systems, and how
biofilms and other factors affect the wound-healing process. Controlling
and preventing infection is of utmost importance for normal wound healing.
Rational use of anti-infectious agents is crucial and is particularly relevant
in the context of rising healthcare costs. Knowledge of the complex
relationship between hard-to-heal wounds, biofilm formation and wound
healing is vital for efficient management of hard-to-heal wounds.
Key words: Hard-to-heal wounds  ■ Chronic wounds  ■ Chronic wound
infection  ■ Biofilms  ■ Wound healing  ■ Morbidity  ■ Healthcare costs
G
lobally, hard-to heal wounds have become a major
public health problem that incur significant
economic costs. They place a huge burden on
patients, caregivers and society in general and are a
major cause of patient morbidity. In 2012/12, out of a total
estimated cost to the NHS of £5.3 billion to manage patients
with wounds, £3.2 billion was spent on hard-to-heal wounds
(Guest et al, 2015) . In the UK, the number of people with a
wound managed by the NHS was estimated at 2.2 million
patients for 2012/13 (Guest et al, 2015), with the number of
people across Europe living with a hard-to-heal wound across
Maria-Manuel Azevedo, Researcher, Department of Pathology and Center for Research
in Health Technologies and Information Systems, Faculty of Medicine, University of
Porto, Portugal, maria.manuel.azevedo2011@gmail.com
Carmen Lisboa, Teacher, Department of Pathology and Center for Research in Health
Technologies and Information Systems, Faculty of Medicine, University of Porto,
Portugal, and Physician, Department of Dermatovenereology, Centro Hospitalar
Universitário São João, Porto, Portugal
Luís Cobrado, Physician, Department of Pathology and Center for Research in Health
Technologies and Information Systems, Faculty of Medicine, University of Porto,
Portugal
Cidália Pina-Vaz, Teacher, Department of Pathology and Center for Research in Health
Technologies and Information Systems, Faculty of Medicine, University of Porto,
Portugal
Acácio Rodrigues, Teacher and Head, Microbiology Department, Department of
Pathology and Center for Research in Health Technologies and Information Systems,
Faculty of Medicine, University of Porto, Portugal, and Physician, Burn Unit, Department
of Plastic and Reconstructive Surgery, Hospital São João, Porto, Portugal
Accepted for publication: January 2020
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Europe estimated at 1.5-2 million (Lindholm and Searle, 2016.
Meanwhile, in the USA, diabetic foot ulcers and other chronic
wounds affect around 6.5 million people, costing around $25
billion a year (Dhall et al, 2014).
Wounds can be described as dynamic environments in
which a triad of dead tissue, exudate and microbial load
interact in a complex circle between both themselves and with
the host tissue (Vyas and Wong, 2016). They should be
approached as a serious medical issue because they may be
contaminated with a high number of microorganisms, which
delay wound healing and skin proliferation. Ultimately, death
can occur as a result of a devastating systemic infection
(Tian et al, 2015).
This article highlights:
■■ The economic costs associated with hard-to-heal wounds
■■ Discusses the definition of hard-to-heal wounds
■■ Examines the relationship between hard-to-heal wounds
and biofilm formation
■■ Looks at the impact of biofilms on wound healing
■■ Discusses how patients’ risk factors may complicate wound
healing.
Economic costs associated with hard-to-heal
wounds
Wounds are a major cause of patient morbidity and high
healthcare costs, which are increasing the stress on healthcare
systems at a global level (Gupta et al, 2016). The reduction of
infection associated with wounds could result in significant
overall healthcare cost savings. According to the United
Nations, chronic wounds account for 2% of the health budget
in Europe, and 1-2% of the population in developed countries
are expected to experience a hard-to-heal wound at some
point in their lives (Böttrich, 2012).
The number of patients with hard-to-heal wounds is rising
worldwide because of the ageing population and an increase in
the number of people who are obese, have type 2 diabetes or
cardiovascular disease. Furthermore, hard-to-heal wounds are
related to psychosocial issues such as loss of mobility, decreased
bodily function, social problems, poor quality of life and loss of
participation in the workforce (Ennis et al, 2004).
Managing such a critical condition requires quicker
solutions results with scarcer resources. Hospitals are looking
for novel, effective approaches to identify and integrate
cost-effective wound therapies without compromising care
© 2020 MA Healthcare Ltd
quality. Consequently, cost-effectiveness analyses have become
a critical instrument for hospital administrators (Gupta et al,
2016).The challenge arises when trying to balance the initial
higher costs of advanced wound-healing technologies with
overall direct and indirect costs involved in wound care.
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HARD-TO-HEAL WOUNDS
Hard-to-heal wounds
For many years the classification of wounds termed ‘chronic’
has proved a challenge. In 2018, there was an attempt to make
the classification of such wounds consistent at a meeting that
also discussed how they should be described. There was
consensus that the most appropriate description for wounds
previously described as chronic, complex, non-healing or hard-
to-heal should be hard-to-heal wounds. A consensus
document published following the meeting has recommended
that any wound that has not healed by 40–50% after 4 weeks
of good standard of care should be considered a hard-to-heal
wound (Atkin et al, 2019).
In hard-to-heal wounds, the usual biological progression
of inflammation, angiogenesis, matrix deposition and wound
contraction followed by epithelialisation and scar
remodelling is interrupted so healing is delayed (Jull et al,
2015). Delayed healing is usually related to microbial
colonisation and/or infection, high levels of exudate, wide
tissue loss or exposure of critical structures. Some features,
such as the number of times that the wound is open and
previous attempts to close it are useful when describing the
timeline until closure. The most common hard-to-heal
cutaneous wounds are venous, arterial and neuropathic leg
ulcers and pressure ulcers (Gupta et al, 2016).
The key factors in promoting wound healing are
debridement (surgical or chemical), infection control (local
application of antiseptics or antimicrobials versus systemic
administration) and wound dressings. Skin grafting or skin
substitutes and growth factors could be valuable in some
hard-to-heal ulcers.
A crucial step to treat any wound is debridement to remove
all foreign material or necrotic tissue that may be harmful until
the wound edges and base are formed of normal, healthy
tissue. Debriding an acute wound enables it to go through the
normal wound-healing phases, assuming that both systemic
and local factors are working normally (Kirshen et al, 2006).
Adequate surgical debridement is a prerequisite for the
successful treatment of skin, soft tissue and bone infection
(Diefenbeck et al, 2013). Aggressive debriding of a hard-to-
heal wound aids its change into an acute wound so it can
progress through the normal phases of wound healing.
Recurrent debridement removes inhibitors of wound healing
and allows growth factors to function more successfully
(Trengove et al, 1999).
Some studies have emphasised the central importance of
wound irrigation to the process of wound healing. Wound
irrigation involves the steady flow of a solution across an open
wound to create an optimal environment for healing,
improving hydration and facilitating the removal of deep
debris, wound exudate and metabolic waste (Rodeheaver,
1999; Fernandez and Griffiths, 2008).
Biofilms and hard-to-heal wound infection:
a dynamic relationship
Unfortunately, wounds are highly susceptible to bacterial
infection (Becerra et al, 2016). Bacterial infection in a wound
follows an ‘exponential progression’, with bacterial replication
and production of a polymeric matrix. This matrix promotes
adherence to any inert or living surface, allowing bacteria to
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thrive in hostile environments (Davey and O’Toole, 2000).
This forms a structure called a biofilm (Donlan and Costerton,
2002), which is highly resistant to topical and systemic
antibacterial compounds unless disrupted by debridement
(Gabriel et al, 2008).
Biofilms, which occur in nearly all environments around
the world, are communities of independent cells with an
extraordinary degree of organisation, linked by an extracellular
polymeric matrix. All abiotic surfaces submerged in non-sterile
water, such as seawater or fresh water, may develop bacterial
biofilms. Within these surfaces, biofilm can cause major
problems, disturbing pipelines and water supplies, and its
adherence to ships’ hulls reduces performance and increases
fuel consumption. In respect to freshwater pipelines, this
situation is worrying because Pseudomonas aeruginosa and
Legionella pneumophila can easily multiply in water, becoming
waterborne infectious agents (Di Pippo et al, 2018). Bacteria
organised in a biofilm are particularly effective in promoting
their own development by enhancing symbiotic relationships
and granting survival in hostile environments.
Biofilm capacity is an important factor in microbial survival
and pathogenicity, with intricate implications for wound
treatment; for instance, antimicrobial resistance mechanisms in
biofilm may involve increased cell density and physical
exclusion of antimicrobials. Moreover, each individual
microbial cell in a biofilm may undergo changes that increase
resistance to biocides (Edmiston et al, 2016), such as:
■■ Promoted stress response by nutrient limitation with
consequent slow growth
■■ Increased expression of multidrug resistance pumps
■■ Activation of quorum-sensing systems
■■ Changes in the profile of outer membrane proteins.
The biofilm may also contribute to increased microbial
resistance of the microorganism to the host immune system
response by interfering with macrophage phagocytic activity
(Wolcott et al, 2010) or by inactivating antibodies that mediate
phagocytosis and the clearance of microbial cells (Thomsen et
al, 2015).
A study by Wolcott et al (2016) showed that 60–90% of
hard-to-heal wounds have biofilms compared with 6% of
acute wounds. Akers et al (2014), in a study of US military
trauma patients, found that bacterial biofilms were responsible
for approximately 80% of chronic skin infections.
A systematic review of studies on biofilms in hard-to-heal
wounds, including pressure ulcers, venous leg ulcers and
diabetic foot ulcers, found that their prevalence was 78.2%
(Malone et al, 2017).
In clinical practice, bacterial biofilms are a considerable
challenge for health professionals and are widely recognised as
a key factor in increasing patient morbidity. In patients who
are confined to bed, recurrent pressure ulcers are particularly
prone to developing biofilm by both aerobic and anaerobic
bacteria; for that reason, healing is difficult to achieve (Donelli
and Vuotto, 2014).Patients with diabetes are also susceptible to
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developing hard-to-heal dermal and subdermal wounds, which
can be colonised by a high number of diverse bacteria. Data
from the literature stresses that bacterial biofilms are invariably
found in hard-to-heal wounds (Attinger and Wolcott, 2012).
Diabetic foot ulcers, pressure ulcers and chronic venous ulcers
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HARD-TO-HEAL WOUNDS
usually contain Staphylococcus aureus biofilms. It is important to
highlight that some chronic wounds do not heal despite
successive therapeutic approaches, a fact that can be attributed
to the presence of bacteria with a biofilm growth phenotype
(Percival and Bowler, 2004; Davis et al, 2008).
James et al (2008), using scanning electron microscopy,
found microbial aggregates were higher in hard-to-heal
wounds than acute wounds. The interaction between biofilm
and chronic wounds has been investigated using several in
vitro models (Hill et al, 2010; Agostinho et al, 2011). According
to Akers et al (2014), biofilm production is associated with a
prolonged persistence of wound infection. While debridement
is accepted as the gold standard intervention to promote
wound healing, bacterial biofilm can resist debridement and
act as a resistance reservoir, leading to considerable delays in
wound healing.
The presence of bacteria in the wound bed can be divided
into four categories based on the host response: contaminated;
colonised; critically colonised; and infected. All wounds are
contaminated at first, and progress up and down the wound
bioburden in a continuum, depending upon the quantity and
types of microorganisms present.
The most frequently isolated species in hard-to-heal
wounds in humans are Staph aureus, Enterococcus faecalis,
Pseudomonas aeruginosa, coagulase-negative Staphylococci spp and
Proteus spp (Gjødsbøl et al, 2006). Hard-to-heal wounds
provide an ideal culture medium for bacteria and, among
inpatients with chronic leg ulcers and burn wounds, Staph
aureus and P aeruginosa can colonise up to 93.5% and 52.2% of
cases respectively (Serra et al, 2015). Regarding pressure ulcers,
a diversity of colonising bacteria is evident but aerobic
organisms are cultured more often than anaerobes (O’Meara et
al, 2000).The most common species recovered are Staph aureus,
Streptococcus spp, Proteus spp, Escherichia coli, Pseudomonas spp,
Klebsiella spp and Citrobacter spp (Boulton et al, 2007). In the
case of diabetic foot ulcers, P aeruginosa and anaerobes are
frequently isolated, with anaerobes being commonly present in
the discharge of chronic pilonidal sinuses.
It is increasingly recognised that biofilms are the principal
cause of wounds becoming chronic. Progress in treatments for
wound biofilms will increase the range of hard-to-heal
wounds that can be healed and possibly save many
patients’ lives.
Wound healing management
Historically, one of the most elementary and crucial practices
of human civilisation is healing wounds; this can be seen from
Egyptian civilisation papyri to the battlefields of Crimea.
Civilisations in the remote past created bandages and
homemade dressings made from honey, grease and lint
(Broughton et al, 2006), among many other substances
and compounds.
The process of wound healing is complex, involving the
reconstitution of several skin layers. This occurs through four
overlapping phases: haemostasis; inflammation; proliferation;
and remodelling. Haemostasis starts when blood components
extravasate into the site of wound, with platelets being exposed
to collagen and other extracellular components, leading to the
release of clotting factors, growth factors and cytokines
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(Burnouf et al, 2013). During the inflammatory phase, blood
cells such as neutrophils and macrophages infiltrate the wound
bed, remove pathogenic organisms and secrete cytokines to
promote the production of fibroblasts, endothelial cells and
keratinocytes. Two days later, these factors penetrate the wound
massively and increase phagocytic activity. This constitutes a
critical phase leading to the next steps in the healing process.
Thereafter, the proliferation phase when new tissue is
formed takes place, which includes stages such as fibroplasia,
wound matrix deposition, angiogenesis and re-epithelialisation.
The granulation tissue formed by this provides volume to the
wound and facilitates closure by driving wound contraction.
This phase also enables healing by promoting re-
epithelialisation. Substantial angiogenesis is required for the
healing process to occur within this tissue. At the same time,
granulation tissue produces growth factors that favour
proliferation and differentiation of epithelial cells, which
restore epithelial barrier integrity. When the wound is filled,
angiogenesis finishes and many newly formed blood vessels
may undergo apoptosis. In the remodelling phase, a constant
alteration occurs, such as collagen degradation and deposition
in an equilibrium-producing manner.
In hard-to-heal wounds, the steps of this process are not
complete and the tissue remains under oxidative stress owing
to the production of reactive oxygen species, leading to DNA
damage, gene dysregulation, cell death and the development of
an aggressive proteolytic environment (Sen and Roy, 2008).
Sen and Roy (2008) induced oxidative stress by inhibiting two
antioxidant enzymes (catalase and glutathione peroxidase) in a
diabetic mouse model (the db/db mouse model) at the time of
injury. This mechanism was enough to cause wounds to
become chronic.
As mentioned above, wounds may be colonised by a
polymicrobial community with biofilm-producing bacteria
becoming dominant. The expression of several genes is
impaired when reactive oxygen species increases, which makes
bacteria more able to produce virulent attributes involved in
biofilm formation. After treatment with antioxidants such as
α-tocopherol and N-acetylcysteine, oxidative stress may be
reduced, with biofilms recovering at least partial sensitivity to
antibiotics (Dhall et al, 2014).
Prevention and effective management and control of
infection are critical for the normal wound-healing process.
When bacteria on the wound surface start replication and
increase their metabolic activity, the byproducts formed, such
as endotoxins and metalloproteinases, all negatively affect every
phase described above (Warriner and Burrell, 2005). Wound
pathogens such as Staph aureus, P aeruginosa and ß-haemolytic
streptococci cause delayed healing. Causing further direct
damage to the host, bacteria attract leukocytes, with
subsequent amplification of inflammatory cytokines, proteases
and reactive oxygen species, thus both initiating and
maintaining inflammatory cascades (Schreml et al, 2010). The
resulting proteases and reactive oxygen species from both host
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and bacteria degrade the extracellular matrix and growth
factors, disrupting cell migration and inhibiting wound closure
(Demidova-Rice et al, 2012).
Data from the literature show that numerous risk factors
can complicate wound healing and consequently increase
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healthcare costs; these include, in particular, patient age,
pulmonary and vascular disease, haemodynamic instability,
hypoalbuminemia, obesity, uraemia, ascites, nutritional
deficiencies, malignancy, hypertension, the length and depth of
wound, the presence of foreign bodies in the wound, anaemia,
diabetes and smoking, with radiation therapy, steroid use
among several possible iatrogenic factors (Riou et al, 1992;
Abbas and Hill, 2009).
Options to manage and treat hard-to-heal wounds are
invariably intended to:
■■ Identify the risk factors that could make a wound hard to
heal and address these
■■ Provide optimal management of the wound bed
■■ Contribute to progression through the normal phases of the
wound-healing process.
Possible treatments for hard-to-heal wounds
Dressings/advanced dressings
Dressing selection is important and the market is vast
(Frykberg and Banks, 2015; Westby et al, 2017). This includes
dressings that deliver debriding or antimicrobial agents (Gould
et al, 2015), maintain a moist wound environment and
minimise skin irritation or friction (Jones et al, 2018).
Many advanced wound dressings are available, including
those containing alginates, foams, hydrocolloids and hydrogels.
These should be chosen carefully according to the wound type.
Alginate and foam dressings are used to absorb excess exudate.
Silver dressings decrease microbial contamination to enable
a normal healing course (Kalan et al, 2017). Dressings
incorporating iodide and carbon can also reduce the microbial
bioburden (Bansal and Goyal, 2005; Fitzgerald et al, 2017).
Negative pressure wound therapy
Negative pressure wound therapy, which is also called vacuum-
assisted wound closure, is a wound dressing system that
continuously or intermittently applies subatmospheric pressure
to the surface of the wound. It is a suggested treatment for the
management of hard-to-heal wounds such as leg ulcers
because its application is thought to promote the healing
process (Vuerstaek et al, 2006). However, the evidence is
lacking as to its benefits in treating other wound types
(Mendonca et al, 2006).
Biofilm inhibitors
Exogenous delivery of nitric oxide with a prodrug vehicle is
effective against clinically relevant multispecies biofilm (Craven
et al, 2016). Recent studies have examined other biofilm
inhibitors, such as antimicrobial peptides, metal chelators,
quorum-sensing inhibitors and amino acids (Bala et al, 2011;
Sanchez et al, 2014) and nitric oxide (Craven et al, 2016).
D-amino acids were described as inhibiting bacterial
biofilm growth of Gram-positive species such as Bacillus subtilis
and Staph aureus (Kolodkin-Gal et al, 2010; Hochbaum et al,
2011).
© 2020 MA Healthcare Ltd
Conclusion
The number of patients with hard-to-heal wounds continues
to increase worldwide, mainly because the population is ageing
and an increasing number of people are obese, or have type 2
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HARD -TO-HEAL WOUNDS
KEY POINTS
■■ If the normal biological progress of wound healing is interrupted, for
example by infection, the wound can become chronic
■■ Wounds constitute a key cause of patient morbidity at a global level,
placing a great burden on healthcare systems
■■ Wound healing can be complicated by risk factors such as patient
age, pulmonary and vascular disease, haemodynamic instability,
hypoalbuminaemia, obesity, uraemia, ascites, nutritional deficiencies,
malignancy, hypertension, length/depth of wound, presence of foreign
bodies, anaemia, diabetes and smoking
■■ Biofilm formation is implicated in microbial survival/pathogenicity,
increasing resistance to antibacterial compounds with implications for
wound treatment
■■ Prevention and effective management of infection are critical for normal
wound healing
diabetes, or cardiovascular disease. Preventing or controlling
infections is essential for the normal wound-healing process to
occur.
In hard-to-heal wounds, the usual biological progression is
interrupted so healing is delayed. Delayed healing is usually
related to severe microbial colonisation or infection, high levels
of exudate, wide tissue loss or exposure of critical structures.
The extent of biofilm formation is an important factor in
microbial survival and pathogenicity, with complex
implications for wound treatment; for instance, antimicrobial
resistance mechanisms in biofilm may include increased cell
density and physical exclusion of antimicrobials. It is therefore
essential to prevent wounds from becoming chronic and this
may involve many approaches and strategies.  BJN
Declaration of interest: none
Abbas SM, Hill AG. Smoking is a major risk factor for wound dehiscence
after midline abdominal incision; case-control study. ANZ J Surg.
2009;79(4):247–250. https://doi.org/10.1111/j.1445-2197.2009.04854.x
Agostinho AM, Hartman A, Lipp C, Parker AE, Stewart PS, James GA. An in
vitro model for the growth and analysis of chronic wound MRSA biofilms.
J Appl Microbiol. 2011;111(5):1275–1282. https://doi.org/10.1111/
j.1365-2672.2011.05138.x
Akers KS, Mende K, Cheatle KA et al. Biofilms and persistent wound
infections in United States military trauma patients: a case-control analysis.
BMC Infect Dis. 2014;14(1):190. https://doi.org/10.1186/1471-2334-14-
190
Atkin L, Bućko Z, Conde Montero E et al. Implementing TIMERS: the race
against hard-to-heal wounds. J Wound Care. 2019;23(Suppl 3a):S1-S50.
https:// doi.org/10.12968/jowc.2019.28.Sup3a.S1
Attinger C, Wolcott R. Clinically addressing biofilm in chronic wounds.
Adv Wound Care. 2012;1(3):127–132. https://doi.org/10.1089/
wound.2011.0333
Bala A, Kumar R, Harjai K. Inhibition of quorum sensing in Pseudomonas
aeruginosa by azithromycin and its effectiveness in urinary tract infections.
J Med Microbiol. 2011;60(3):300–306. https://doi.org/10.1099/
jmm.0.025387-0
Bansal RC, Goyal M. Activated carbon adsorption. 1st edn. Boca Raton (FL):
CRC Press; 2005
Becerra SC, Roy DC, Sanchez CJ, Christy RJ, Burmeister DM. An optimized
staining technique for the detection of Gram positive and Gram negative
bacteria within tissue. BMC Res Notes. 2016;9(1):216. https://doi.
org/10.1186/s13104-016-1902-0
Böttrich JG. Challenges in chronic wound care: the need for interdisciplinary
collaboration. MedTech Views. 2012. https://tinyurl.com/yyzfm9w8
(accessed 21 January 2020)
Boulton A, Cavanagh P, Rayman G (eds). The foot in diabetes. 4th edn.
S11
Downloaded from magonlinelibrary.com by 130.238.007.040 on March 15, 2020.
HARD-TO-HEAL WOUNDS
Chichester: Wiley, 2007
Broughton G 2nd, Janis JE, Attinger CE. A brief history of wound care. Plast
Reconstr Surg. 2006;117(7 Suppl):6S–11S. https://doi.org/10.1097/01.
prs.0000225429.76355.dd
Burnouf T, Goubran HA, Chen TM, Ou KL, El-Ekiaby M, Radosevic M.
Blood-derived biomaterials and platelet growth factors in regenerative
medicine. Blood Rev. 2013;27(2):77–89. https://doi.org/10.1016/j.
blre.2013.02.001
Craven M, Kasper SH, Canfield MJ et al. Nitric oxide-releasing
polyacrylonitrile disperses biofilms formed by wound-relevant pathogenic
bacteria. J Appl Microbiol. 2016;120(4):1085–1099. https://doi.
org/10.1111/jam.13059
Davey ME, O’Toole GA. Microbial biofilms: from ecology to molecular
genetics. Microbiol Mol Biol Rev. 2000;64(4):847–867. https://doi.
org/10.1128/MMBR.64.4.847-867.2000
Davis SC, Ricotti C, Cazzaniga A, Welsh E, Eaglstein WH, Mertz PM.
Microscopic and physiologic evidence for biofilm-associated wound
colonization in vivo. Wound Repair Regen. 2008;16(1):23–29. https://doi.
org/10.1111/j.1524-475X.2007.00303.x
Demidova-Rice TN, Hamblin MR, Herman IM. Acute and impaired wound
healing: pathophysiology and current methods for drug delivery, part 1:
normal and chronic wounds: biology, causes, and approaches to care. Adv
Skin Wound Care. 2012;25(7):304–314. https://doi.org/10.1097/01.
ASW.0000416006.55218.d0
Dhall S, Do DC, Garcia M et al. Generating and reversing chronic wounds in
diabetic mice by manipulating wound redox parameters. J Diabetes Res.
2014;2014:1–18. https://doi.org/10.1155/2014/562625
Diefenbeck M, Haustedt N, Schmidt HGK. Surgical debridement to optimise
wound conditions and healing. Int Wound J. 2013;10(Suppl 1):43–47.
https://doi.org/10.1111/iwj.12187
Di Pippo F, Di Gregorio L, Congestri R, Tandoi V, Rossetti S. Biofilm growth
and control in cooling water industrial systems. FEMS Microbiol Ecol.
2018;94(5). https://doi.org/10.1093/femsec/fiy044
Donelli G,Vuotto C. Biofilm-based infections in long-term care facilities.
Future Microbiol. 2014;9(2):175–188. https://doi.org/10.2217/fmb.13.149
Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant
microorganisms. Clin Microbiol Rev. 2002;15(2):167–193. https://doi.
org/10.1128/CMR.15.2.167-193.2002
Edmiston CE, McBain AJ, Kiernan M, Leaper DJ. A narrative review
of microbial biofilm in postoperative surgical site infections: clinical
presentation and treatment. J Wound Care. 2016;25(12):693-702. https://
doi.org/10.12968/jowc.2016.25.12.693
Ennis WJ,Valdes W, Salzman S, Fishman D, Meneses P. Trauma and wound care.
In: Morison MJ, Ovington LG, Wilkie K. Chronic wound care: a problem-
based learning approach. New York (NY): Mosby; 2004: 291–307
European Pressure Ulcer Advisory Panel. Summary report on the prevalence of
pressure ulcers. EPUAP Review. 2002;4:49–57
Fernandez R, Griffiths R. Water for wound cleansing. Cochrane Database
Syst Rev. 2008;2(1):CD003861. https://doi.org/10.1002/14651858.
CD003861.pub2
Fitzgerald DJ, Renick PJ, Forrest EC et al. Cadexomer iodine provides superior
efficacy against bacterial wound biofilms in vitro and in vivo. Wound
Repair Regen. 2017;25(1):13–24. https://doi.org/10.1111/wrr.12497
Frykberg RG, Banks J. Challenges in the treatment of chronic wounds.
Adv Wound Care. 2015;4(9):560–582. https://doi.org/10.1089/
wound.2015.0635
Gabriel A, Shores J, Heinrich C et al. Negative pressure wound therapy with
instillation: a pilot study describing a new method for treating infected
wounds. Int Wound J. 2008;5(3):399–413. https://doi.org/10.1111/j.1742-
481X.2007.00423.x
Gjødsbøl K, Christensen JJ, Karlsmark T, Jørgensen B, Klein BM, Krogfelt
KA. Multiple bacterial species reside in chronic wounds: a longitudinal
study. Int Wound J. 2006;3(3):225–231. https://doi.org/10.1111/j.1742-
481X.2006.00159.x
Gould L, Abadir P, Brem H et al. Chronic wound repair and healing in
older adults: current status and future research. Wound Repair Regen.
2015;23(1):1–13. https://doi.org/10.1111/wrr.12245
CPD reflective questions
■■ What can you do to prevent chronic wounds and associated diseases?
■■ How can health professionals contribute to infection control?
■■ Are hospital facilities’ hygiene conditions adequate to prevent the spread of infections?
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Guest JF, Ayoub N, McIlwraith T et al. Health economic burden that
wounds impose on the National Health Service in the UK. BMJ Open.
2015;5(12):e009283. https://doi.org/10.1136/bmjopen-2015-009283.
Gupta S, Gabriel A, Lantis J, Téot L. Clinical recommendations and practical
guide for negative pressure wound therapy with instillation. Int Wound J.
2016;13(2):159–174. https://doi.org/10.1111/iwj.12452
Hill KE, Malic S, McKee R et al. An in vitro model of chronic wound
biofilms to test wound dressings and assess antimicrobial susceptibilities. J
Antimicrob Chemother. 2010;65(6):1195–1206. https://doi.org/10.1093/
jac/dkq105
Hochbaum AI, Kolodkin-Gal I, Foulston L, Kolter R, Aizenberg J, Losick R.
Inhibitory effects of D-amino acids on Staphylococcus aureus biofilm
development. J Bacteriol. 2011;193(20):5616–5622. https://doi.
org/10.1128/JB.05534-11
James GA, Swogger E, Wolcott R et al. Biofilms in chronic wounds. Wound
Repair Regen. 2008;16(1):37–44. https://doi.org/10.1111/j.1524-
475X.2007.00321.x
Jones RE, Foster DS, Longaker MT. Management of chronic wounds—2018.
JAMA. 2018;320(14):1481–1482. https://doi.org/10.1001/
jama.2018.12426
Jull AB, Cullum N, Dumville JC, Westby MJ, Deshpande S, Walker N.
Honey as a topical treatment for wounds. Cochrane Database Syst Rev.
2015;6(3):CD005083. https://doi.org/10.1002/14651858.CD005083.
pub4
Kalan L, Zhou M, Labbie M, Willing B. Measuring the microbiome of chronic
wounds with use of a topical antimicrobial dressing—a feasibility study.
PLoS One. 2017;12(11):e0187728. https://doi.org/10.1371/journal.
pone.0187728
Kirshen C, Woo K, Ayello EA, Sibbald RG. Debridement. Adv Skin
Wound Care. 2006;19(9):506–517. https://doi.org/10.1097/00129334-
200611000-00011
Kolodkin-Gal I, Romero D, Cao S, Clardy J, Kolter R, Losick R. D-amino
acids trigger biofilm disassembly. Science. 2010;328(5978):328: 627–629.
https://doi.org/10.1126/science.1188628
Lindholm C, Searle R. Wound management for the 21st century: combining
effectiveness and efficiency. Int Wound J. 2016;13(Suppl 2):5-15. https://
doi.org/10.1111/iwj.12623
Malone M, Bjarnsholt T, McBain AJ et al. The prevalence of biofilms in chronic
wounds: a systematic review and meta-analysis of published data. J Wound
Care. 2017;26(1):20-25. https://doi.org/10.12968/jowc.2017.26.1.20
Mendonca DA, Papini R, Price PE. Negative-pressure wound therapy: a
snapshot of the evidence. Int Wound J. 2006;3(4):261-71. https://doi.
org/10.1111/j.1742-481X.2006.00266.x
O’Meara S, Cullum N, Majid M, Sheldon T. Systematic reviews of wound care
management: (3) antimicrobial agents for chronic wounds; (4) diabetic
foot ulceration. Health Technol Assess. 2000;4(21):1–237. https://doi.
org/10.3310/hta4210
Percival SL, Bowler PG. Biofilms and their potential role in wound healing.
Wounds. 2004;16(7):244–240. https://www.woundsresearch.com/
article/2870 (accessed 21 January 2020)
Riou JPA, Cohen JR, Johnson H Jr. Factors influencing wound dehiscence.
Am J Surg. 1992;163(3):324–330. https://doi.org/10.1016/0002-
9610(92)90014-I
Rodeheaver GT. Pressure ulcer debridement and cleansing: a review of current
literature. Ostomy Wound Manage 1999;45:(1A Suppl):80S–87S
Sanchez CJ Jr, Akers KS, Romano DR et al. D-amino acids enhance the activity
of antimicrobials against biofilms of clinical wound isolates of Staphylococcus
aureus and Pseudomonas aeruginosa. Antimicrob Agents Chemother.
2014;58(8):4353–4361. https://doi.org/10.1128/AAC.02468-14
Schreml S, Szeimies RM, Prantl L, Karrer S, Landthaler M, Babilas P. Oxygen
in acute and chronic wound healing. Br J Dermatol. 2010;163(2):257–268.
https://doi.org/10.1111/j.1365-2133.2010.09804.x
Sen CK, Roy S. Redox signals in wound healing. Biochimica et Biophysica
Acta. 2008;1780(11):1348–1361. https://doi.org/10.1016/j.
bbagen.2008.01.006
Serra R, Grande R, Butrico L et al. Chronic wound infections: the role of
Pseudomonas aeruginosa and Staphylococcus aureus. Expert Rev Anti
© 2020 MA Healthcare Ltd
British Journal of Nursing 2020, Vol 29, No 5: TISSUE VIABILITY SUPPLEMENT
Downloaded from magonlinelibrary.com by 130.238.007.040 on March 15, 2020.
 HARD -TO-HEAL WOUNDS

Infect Ther. 2015;13(5):605–613. https://doi.org/10.1586/14787210.201 jvs.2006.07.030

5.1023291
Thomsen K, Christophersen L, Bjarnsholt T, Jensen PØ, Moser C, Høiby N.
Anti-Pseudomonas aeruginosa IgY antibodies induce specific bacterial
aggregation and internalization in human polymorphonuclear neutrophils.
Infect Immun. 2015;83(7):2686-93. https://doi.org/10.1128/IAI.02970-
14. Epub 2015 Apr 20.
Tian G, Guo Y, Zhang L. Non-invasive treatment for severe complex pressure
ulcers complicated by necrotizing fasciitis: a case report. J Med Case
Reports. 2015;9(1):220. https://doi.org/10.1186/s13256-015-0703-8
Trengove NJ, Stacey MC, Macauley S et al. Analysis of the acute and chronic
wound environments: the role of proteases and their inhibitors. Wound
Repair Regen. 1999;7(6):442–452. https://doi.org/10.1046/j.1524-
475X.1999.00442
Vuerstaek JD,Vainas T, Wuite J, Nelemans P, Neumann MH,Veraart JC.
State-of-the-art treatment of chronic leg ulcers: a randomized controlled
trial comparing vacuum-assisted closure (V.A.C.) with modern wound
dressings. J Vasc Surg. 2006;44(5):1029-1037. https://doi.org/10.1016/j.
Vyas KS, Wong LK. Detection of biofilm in wounds as an early indicator
for risk for tissue infection and wound chronicity. Ann Plast Surg.
2016;76(1):127–131. https://doi.org/10.1097/SAP.0000000000000440
Warriner R, Burrell R. Infection and the chronic wound: a focus on
silver. Adv Skin Wound Care. 2005;18(Suppl 1):2–12. https://doi.
org/10.1097/00129334-200510001-00001
Westby MJ, Dumville JC, Soares MO, Stubbs N, Norman G. Dressings and
topical agents for treating pressure ulcers. Cochrane Database Syst Rev.
2017;6(6):CD011947. https://doi.org/10.1002/14651858.CD011947.
pub2
Wolcott RD, Hanson JD, Rees EJ et al. Analysis of the chronic wound
microbiota of 2,963 patients by 16S rDNA pyrosequencing. Wound Repair
Regen. 2016;24(1):163–174. https://doi.org/10.1111/wrr.12370
Wolcott RD, Rumbaugh KP, James G. Biofilm maturity studies indicate sharp
debridement opens a time-dependent therapeutic window. J Wound Care.
2010;19(8):320-328. https://doi.org/10.12968/jowc.2010.19.8.77709

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