REVIEW
DOMINATE Wounds
WOUNDS 2014;26(1):1-12
From the 1Jobst Vascular Institute,
Toledo, OH; 2Institute for Advanced
Wound Care, Montgomery, AL;
3
Georgia Regents University,
Augustus, GA; 4University Hospitals
Case Medical Center, Cleveland,
OH; 5Medical University of Vienna,
Vienna, Austria; 6Center for Curative
and Palliative Wound Care, Calvary
Hospital, Bronx, NY; 7University of
North Dakota College of Nursing,
Grand Forks, ND; 8MEP Healthcare
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Dietary Services, Inc, Evansville, IN;
9
ProMedica Wound Care, Toledo, OH;
10
Hanger Orthotics, Toledo, OH
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Address correspondence to:
Steven Gale, MD
2109 Hughes Drive, Suite 400
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Toledo, OH 43606
ssgale@bex.net
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Disclosure: The authors disclose
no financial conflicts of interest.
Dr. Treadwell and Dr. Alvarez
are members of the WOUNDS
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editorial board, and, as such, were
not involved in the review of this
manuscript.
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Steven S. Gale, MD, FACS1; Fedor Lurie, MD, PhD1; Terry Treadwell,
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MD2; Jose Vazquez, MD3; Teresa Carman, MD4; Hugo Partsch, MD5;
Oscar Alvarez, PhD6; Diane Langemo, PhD, RN, FAAN7; Mary
Ellen Posthauer, RD, LD, CD8; Mary Cheney, RN, NP-C9; Matthew M.
Wilkin, DPM, ACFAS9; Michael Bursztynski, CO10
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Abstract: Chronic wounds are a significant health problem worldwide.
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Often they are initially managed with various focal treatments until a
specialist becomes involved, sometimes weeks or months after treat-
ment has begun. Even at the specialist level, practices and guide-
lines are inconsistent due to a lack of high-level evidence. A disease
management system for chronic wounds that is simple, practical, and
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adoptable by a variety of wound care practitioners is needed. Such
a system would guide wound care providers to address the critical
aspects of wound care in a prioritized, systematic sequence, leading
to faster healing of simple wounds, and timely advancement to more
complex therapies for wounds that require such treatment. This paper
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describes an empirically developed wound care management system
that has been successfully implemented and provides evidence-based
rationale for each of its components. Relatively simple and practical,
this system organizes an approach to any type of wound, routine or
complex.
Key words: chronic ulcers, clinical management, negative pressure,
debridement
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he field of wound care is rapidly expanding. Treatment options are
continually being added to the armamentarium of wound care pro-
viders. Wound literature is steadily growing, practice guidelines are
being developed, and industry is capitalizing on the widespread interest in
the field. More evidence-based wound care recommendations are appear-
ing and educational opportunities abound.
Chronic wounds are such a significant health problem worldwide that
they are considered the new global epidemic.1 These wounds are often
initially managed with various focal treatments, commonly for weeks or
months, until involving a specialist. Even then, practices are inconsistent
among practitioners and clinics, and although numerous guidelines are
available, they are also inconsistent, mainly due to the lack of high-level
evidence.2 This situation indicates a need for a disease management sys-
tem for chronic wounds that is simple, practical, and can be adopted by
a broad variety of wound care practices. Such a system will guide wound
care providers to address the aspects of wound care in a prioritized, sys-
Vol. 26, No. 1 January 2014 1
 Gale et al
tematic sequence and may lead to faster healing of sim-
ple wounds and timely advancement to more complex
therapies for problematic wounds.
The purpose of this manuscript is to describe an em-
pirically developed wound care management system
that has been successfully implemented and to provide
evidence-based rationale for each of its components. The
elements are provided in the acronym DOMINATE and
can be applied in most wound scenarios as a checklist
to ensure that measures of proven efficacy are being
used to encourage healing, which involves the orderly
progression through 4 phases: hemostasis, inflammation,
proliferation (repair), and maturation (remodeling). It can
also serve as a clinical practice guideline to standardize
management of chronic wound and makes sense in view
of the prevalence and staggering cost of care of chronic,
nonhealing wounds ( > $50 billion/year) in the United
wound care by encouraging cost effectiveness through
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States alone.3 The implementation of the 2010 Affordable
Care Act in the United States very likely will influence
reimbursement formulae. Utilizing therapy proven to as-
sist wound healing and employing clinical practice guide-
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lines in a standardized approach to all wounds may be-
come mandated or linked to reimbursement.
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The DOMINATE Acronym
D-Debridement converts a chronic or stalled wound
to one that is acute by removing nonviable tissue that
can stimulate excessive inflammation and bacterial
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growth. It can reduce the impediment to healing caused
by biofilm and infection, and help the wound progress
out of the inflammatory phase and into the proliferative
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phase. Debridement also removes the senescent cells
that are unresponsive to growth factor and cytokines.
Removal of these cells makes way for healthy, respon-
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sive cells in the wound environment or that are applied
to the wound via cell-containing products. Debridement
can be accomplished by a variety of techniques includ-
ing sharp (eg, scalpel, curette, scissors), enzymatic (eg,
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collagenase), mechanical (eg, wet-to-dry dressings, ultra-
sound), autolytic (eg, foam dressings, hydrogel, and me-
dicinal honey, which also has an osmotic effect), and bio-
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logic (eg, maggot therapy). A combination of techniques
can optimize effectiveness, with sharp debridement as
the default. It has been established that maintenance de-
bridement is necessary and effective in achieving heal-
ing of chronic wounds.4
One precautionary note is in dealing with wounds
due to pyoderma gangrenosum, which is often asso-
2 WOUNDS www.woundsresearch.com
ciated with rheumatoid arthritis and ulcerative colitis.
Surgical debridement can exacerbate these wounds
through a process known as pathergy. Other than isch-
emic wounds, which require restoration of adequate
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blood supply prior to any significant debridement,
there are no other wounds that present contraindica-
tions to debridement.
O-Offloading eliminates wound stress and trauma,
factors known to interfere with healing by destroying
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the matrix and cell regeneration that normally occurs
in the proliferative phase. Offloading also allows epi-
thelialization and remodeling to progress undisturbed
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by pressure, especially if said pressure is accompanied
by a rubbing effect that can break down new tissue. A
common example of this is a diabetic foot wound in the
presence of neuropathy. Using various splints, boots, cus-
tomized shoes, and casts can eliminate this type of pres-
sure. Usually an orthotist is involved with the fitting and
manufacture of these devices. The importance of wear-
ing the offloading device must repeatedly be stressed
to patients; individuals who wear their prescribed foot-
wear at least 60% of the time have 50% greater ulcer
free intervals compared to less compliant patients.5
Wearing the offloading devices outside of the home but
not while at home is also associated with increased rate
of breakdown and ulcer recurrence.6
Pressure ulcers, which represent an enormous ongo-
ing health care problem, are painful, costly, and in many
cases, preventable. In 2001 the National Pressure Ulcer
Advisory Panel7 estimated acute care pressure ulcer
prevalence at 15% and incidence at 7%. Numerous ar-
ticles8-11 have been written addressing the problem of
pressure ulcers and progress in prevention efforts is
being made through education. Offloading the boney
prominences prone to pressure is the mainstay of pre-
vention and treatment. This problem is so pervasive
throughout the United States health care systems, and
so often preventable, that reimbursement denial is now
being linked to its presence in certain circumstances.12
M-Moisture imbalance must be corrected for heal-
ing to progress. Chronic wound exudates contain high
levels of matrix metalloproteinases (eg, collagenases,
elastases), inflammatory cells, and other wound healing
inhibitory factors. Choosing the proper absorbent dress-
ing can control the exudate and help prevent break-
down of new collagen scaffolding and neovasculature in
the proliferative phase.13 Wounds that are too dry, on the
other hand, also are disadvantaged since new cells will
die if they dessicate. If a wound is too wet or too dry,
 Gale et al

Table 1. Characteristics of wound care dressings.

Product type Descriptor Indications Advantages Caveats

CLASS: Absorbent

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Foam Absorbent polyurethane Exudating venous ulcers Permeable, absor- Avoid using on dry
center, semiocclusive and deep cavity wounds bent, insular, cuts wounds
outer layer easily, long wearing
Calcium alginate Kelp derivative Na-Ca Exudating wounds, he- Autolytic debride- Needs secondary dress-
ion exchange forms NA mostasis after debride- ment, hemostatic, ing; watch for retained

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alginate gel ment packs deep wounds dressing and infection
CLASS: Hydrating
Hydrogel Nonadhesive, gelling Dry, sloughy wounds Helps autolytic de- Avoid on ischemic ulcers;

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agent, sheets or rope bridement, cools and requires frequent dressing
soothes changes; gram-negative
proliferation
Hydrocolloid Outer foam, middle gel, Venous, diabetic, and Comfortable for Avoid on ischemic ulcers,
inner adhesive decubitus ulcers, partial patients, no second infection, and vasculitis;

the new cells do not thrive and healing is impaired. In

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thickness wounds, burns dressing necessary

the past, it was the custom to use wet-to-dry dressings

impermeable; can overhy-
drate and leak

ment would be advisable, if only temporarily, to help the

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but that has now been replaced by dressings that main-
tain a moist wound environment. Occasionally, for the
purpose of a short course of mechanical debridement,
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wound heal.
M-Mental health issues such as depression can affect
treatment compliance and should be identified and ad-
dressed.

a wet-to-dry dressing will be used.14 There are numer-
ous dressing choices available and these include silver,
iodine, medicinal honey, hydrogels, foam, alginates, and
collagen. Its important to choose the proper dressing
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I-Infection in wounds continues to be a challenging
problem and represents a considerable health care bur-
den. When infection is present, wounds may become ar-
rested in either the inflammatory or proliferative phases

based on wound drainage or dryness. Characteristics of of healing. Antimicrobial therapy, often in conjunction
absorbent and hydrating wound care dressings current- with debridement, may be necessary. With increasing
ly in use are described in Table 1. complexity and antimicrobial resistance, prompt and ap-
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M-Malignant transformation can occur in wounds propriate intervention is more important than ever. In ad-
that have usually been present > 3 months. If these dition, it is beneficial to include an infectious disease spe-
wounds have not responded to treatment by that time, cialist as a member of the multidisciplinary wound care
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they should be biopsied. Clinical settings that may in-
crease the diagnostic yield include chronic inflamma-
tion from wound sinus, burn scars, radiation, immuno-
suppression, known systemic malignancy (especially
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team early in the treatment process.
Microorganisms are common in chronic wounds and
are often the reason healing fails. It is well known that
control of bioburden is an important aspect of wound

lymphoma or leukemia since skin infiltrates can ulcer- management.17 Chronic wounds can become contami-
ate), and change in ulcer appearance.15,16 A full-thickness nated and/or colonized with either bacteria and/or fun-
punch biopsy that includes the wound bed, subcutane- gi.18 However, when the microorganisms become inva-
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ous, and surrounding tissue, with the patient under local
anesthesia, is adequate.
M-Medications, such as steroids (eg, prednisone),
immunosuppressants (eg, methotrexate), and chemo-
therapeutic agents, can interfere with wound healing. In
cases of chronic wounds, a risk-benefit analysis should
be performed to determine whether medication adjust-
sive, critical colonization can result and, if left untreated,
wound infection may develop. Several mnemonics are
helpful in differentiating critical colonization and infec-
tion by way of wound characteristics. This can assist in
the decision on whether to utilize topical or systemic
antimicrobials. Nonhealing, Exudate, Red friable tissue,
Debris, and Smell (NERDS) would suggest the wound
Vol. 26, No. 1 January 2014 3
 Gale et al
has reached a critical colonization point and initiating
antimicrobial treatment with topical agents along with
debridement would be appropriate. On the other hand,
Size enlargement, Temperature increase, Os/bone ex-
posed, New breakdown, Exudate, Erythema, Edema, and
Smell (STONES) suggests infection and requires system-
ic antimicrobial treatment.19-21
Wound sepsis has been associated with deep tissue
quantitative microbial counts of >100,000 colony-form-
ing units/gram of tissue. In practice, quantitative wound
biopsies are not routinely performed since semiquan-
titative surface wound swabs tend to correlate well
with deep tissue quantitative counts using the Levine
Technique.22 The Levine Technique involves rotating the
swab over a small area (1 cm2) of the wound to extract
fluid, ensuring that no contact is made with the wound
edges. Topical antibacterial therapy such as silver dress-
ings, honey, mupiricin, and iodine compounds can be
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used to treat colonized wounds, but systemic antibiotics
are usually also necessary if the wound is infected.19,21
It is now appreciated that microbes often reside
in a biofilm community firmly attached to the wound
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and protected by an extracellular polymeric substance
(EPS).23,24 All chronic wound infections share these
characteristics and it has been suggested25 that biofilms
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play a role in the prevention of wound healing. The EPS
provides capsule-like protection for the community of
microorganisms, and thus, confers resistance to antimi-
crobials and host-immune responses. Chronic wounds
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tend to have more anaerobes than acute wounds and
these may not be identified on routine swabs unless
specific culture techniques are utilized. The importance
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of adequate and repetitive debridement of necrotic tis-
sue in chronic wounds cannot be overemphasized. This
material provides an efficient growth medium for mi-
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croorganisms and contributes to the development and
maintenance of the biofilm. Continuous and aggressive
maintenance debridement reduces the necrotic burden,
microbial bioburden, excessive exudate, and biofilm.
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Antimicrobial resistance has become a problem not
only in the hospital setting, but also in the community,
because of the overuse and misuse of community pro-
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vided antimicrobials.26-28 Judicious antimicrobial use is
critical and all open wounds do not require antimicrobi-
als unless they are infected.
The treatment of chronic wounds and acute or chron-
ic infections can be challenging. Pragmatic suggestions
to assist wound healing when infection is a consider-
ation include consultation with an infectious disease
4 WOUNDS www.woundsresearch.com
specialist; considering the possibility of anaerobic and
fungal organisms when culturing; using systemic anti-
biotics judiciously to reduce microbial resistance; and
performing maintenance debridement to control necro-
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sis and biofilm
I-Inflammation can cause chronic wounds, especially
leg ulcers, to become stuck in the inflammatory phase
of wound healing often associated with infection.29 A
major contributing factor can be an excess of matrix
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metalloproteinases (MMPs) with resultant destruction
of collagen and the wound matrix. Doxycycline has a
long history as a collagenase inhibitor and can inhibit
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MMPs, as well as covering Methicillin-resistant Staphy-
lococcus aureus, which is becoming increasingly com-
mon.30 Topical application of a 1% doxycycline cream to
reduce wound proteases has also been recommended.31
Protease-reducing dressings, such as oxidized regener-
ate cellulose, collagen, and silver,32 can also be helpful,
as can the use of pentoxifylline 300 mg tid orally.33 Non-
steroidal anti-inflammatory drugs can be added to the
therapeutic mix.
N-Nutrition is a key player in successful wound treat-
ment, particularly for individuals with chronic wounds,
pressure ulcers, and diabetic ulcers. Early identification
of malnutrition and the correction of nutritional defi-
cits promotes wound healing. Patients at nutritional risk
will benefit from early referral to a registered dietician
(RD). Significant weight loss should immediately raise
a red flag for nutritional risk and impaired wound heal-
ing. Without adequate nutrition, it becomes difficult for
wounds to progress, especially through the proliferative
phase of healing.
Adequate energy (30-35 calories/kg/day) is essential
to meet the increased nutritional and metabolic needs
of individuals with wounds. These caloric needs may
be met with carbohydrates, proteins, and fats. With ade-
quate renal function, the protein requirement increases
to 1.25-1.50 grams/kg/day for synthesis of collagen, anti-
bodies, and enzymes. Foods that supply all the essential
amino acids, such as meat, fish, poultry, and dairy, should
be the primary nutritional source to promote collagen
synthesis, and amino acids such as L-arginine and gluta-
mine become conditionally essential with sepsis, burns,
and large wounds.Through adenosine triphosphate pro-
duction, carbohydrates supply energy for the cellular
chemical reactions; if this nutrient is deficient, proteins
will be broken down for energy, further compounding
the protein deficiency. Fat will be utilized only after de-
pletion of protein and carbohydrates.

Hydration is important, especially with fluid loss from
draining wounds, and patients without cardiac or renal
insufficiency require 30 ml/kg/day or more of fluids.The
micronutrient vitamins C, A, E, K, zinc, and copper all
have a role in wound healing. Mega doses may not be
as effective as once believed, especially with vitamin C
(ascorbic acid), due to the bodys excretion of the ex-
cess dosage.34
All interventions should be individualized based on
the current condition of the patient. An obese individ-
ual with a Body Mass Index > 35 may be malnourished
and have additional issues such as edema and infection,
which are significant factors. The multidisciplinary ap-
proach, which would include working with an RD, can
help address these issues.
AArterial insufficiency, peripheral arterial disease
(PAD), and atherosclerosis can be a significant impedi-
ment to wound healing since tissue oxygenation is es-
sential for wounds to heal. Wounds may not progress
beyond the inflammatory phase if the lack of oxygen
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reduces leukocyte-killing capacity.This situation is often
encountered in wounds with compromised local blood
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supply such as deep diabetic, arterial, and pressure ul-
cers. Patients with significant PAD often complain of
calf cramping when walking short distances (intermit-
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tent claudication) or pain in their foot or toes. The foot
is usually cool, often pale, and pulseless. Doppler signals
may be present but are sluggish and abnormal.The pres-
ence of atherosclerotic risk factors, such as tobacco us-
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age and diabetes, can also increase the level of suspicion.
Documentation of the degree of arterial insufficiency is
initially accomplished with noninvasive testing in the
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vascular laboratory. Ankle-brachial indices (ABI) of < 0.7
or transcutaneous oximetry (TCOM, also known as ar-
terial blood gas of the skin) < 40 Torr can be a clue to
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underlying arterial insufficiency that might need correc-
tion if the wound is to heal. Restoring adequate blood
supply to the ulcerated area brings the necessary oxy-
gen to the tissue and helps wound bed preparation.With
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modern surgical techniques, this can often be accom-
plished with minimally invasive procedures that have a
lower risk of complications than open operations, espe-
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cially for high-risk patients with multiple comorbidities.
Tried-and-true bypass procedures, however, still have a
role in the revascularization of individuals for whom the
surgery poses a good risk, especially if an autogenous
vein is used.35
T-Technical advances include hyperbaric oxygen
therapy, negative pressure wound therapy, cell therapy
Gale et al
and bioengineered skin substitutes, acellular therapy/
extracellular matrix, and therapeutic angiogenesis.
These modalities can help move the wound through the
phases of healing when progress stalls. Edema control,
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moisture balance, upregulation of growth factors and
cytokines, angiogenesis, tissue oxygenation, leukocyte
phagocytosis, wound contraction, and coverage can be
enhanced by these wound care techniques.
It is generally accepted that a reasonable goal is heal-
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ing by 12 weeks. This can often be achieved with dia-
betic ulcers. Venous ulcers can take longer; if they dem-
onstrate less than 40% healing after 4 weeks of good
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therapy, they are unlikely to heal at 24 weeks, the an-
ticipated time for healing of most venous ulcers.36 Heal-
ing rates at 4 weeks predict overall healing rates, and
a 10-15% area reduction weekly suggests an excellent
prognosis.36, 37 In the case of venous and diabetic ulcers,
healing rates of less than 40% and 50%, respectively, after
1 month of good wound care (appropriate elements
of DOMINATE Wounds adequate debridement, offload-
ing, moisture balance, bioburden control, nutritional as-
sessment, adequate blood supply, edema control) should
serve as a cue for the practitioner to at least consider
some of the technical advances available.38 The impor-
tant point is that if the wound is not healing in a month
or so, do something different.
Hyperbaric oxygen therapy (HBOT) is an adjunctive
treatment to standard multidisciplinary wound care. Hy-
poxia, one reason chronic wounds fail to heal, can exist
at the cellular level even though pulses are palpable. Hy-
perbaric oxygen therapy is not a substitute for potential
revascularization but can be added if tissue hypoxia per-
sists. Research suggests HBOT is beneficial as adjunctive
treatment for a number of conditions including diabetic
foot ulcers Wagner grade 3 and 4, chronic refractory os-
teomyelitis, compromised flaps and skin grafts, delayed
radiation injuries, and soft tissue radionecrosis.39-41 Other
wounds that may benefit are chronic pressure, arterial,
and venous ulcers; thermal burns; crush injuries; and gas
gangrene.42
During HBOT, the patient breathes 100% oxygen
while inside a monoplace or multiplace hyperbaric
treatment chamber pressurized to greater than sea level,
usually 2.0-3.0 atmospheric pressure absolute for 90
minutes. This significantly increases the amount of oxy-
gen dissolved in the blood plasma, and the effects of this
oxygenation on wound tissue lasts much longer than
the time the patient is in the chamber. Edema and con-
gestion can be reduced by the vasoconstrictive effect
Vol. 26, No. 1 January 2014 5
 Gale et al
of HBOT. Leukocyte bactericidal effect on both aerobic
and anaerobic organisms is enhanced, since neutrophils
require oxygen to phagocytize and kill microorganisms
and tissue oxygen tensions < 30 mm Hg can significantly
reduce this function.
The diabetic foot ulcer is one of the most common
and devastating complications of diabetes and is asso-
ciated with considerable morbidity and mortality. The
major causes of these ulcers are repetitive trauma, of-
ten from pressure with loss of protective sensation due
to neuropathy. Ischemia/hypoxia and infection may be
contributing factors that HBOT can help reverse, pro-
viding there is no limb-threatening ischemia; without
revascularization, HBOT alone is unlikely to improve the
outcome. However, when HBOT is used as adjunctive
therapy in cases of soft tissue infection, impaired heal-
ing from osteomyelitis and persistent non limb-threaten-
ing ischemia, wound healing outcomes are improved.40
Hyperbaric oxygen therapy is an approved, safe medi-
cal procedure and has been proven to enhance healing
of difficult wounds when used as part of a multidisci-
plinary wound care approach. It provides immediate
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support to poorly perfused tissue in areas of compro-
mised blood flow. It should not replace established
wound care management but rather be an adjunctive
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treatment modality. Hyperbaric oxygen therapy can pro-
vide direct cost savings by successfully resolving diffi-
cult and expensive wounds.41
Negative pressure wound therapy (NPWT), which in-
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volves applying subatmospheric pressure to the wound
site, was first described in 1997.43,44 In early animal stud-
ies, NPWT increased laser Doppler blood flow in the
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subcutaneous and muscular tissue, increased the rate of
granulation tissue formation, decreased bacterial coloni-
zation, and improved survival of compromised experi-
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mental flaps.43 Negative pressure wound therapy alters
tissue perfusion in the base of the wound and at the
wound edges, changes which are clinically beneficial,
possibly relating to alterations in cytokines and growth
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factor expression responsible for wound healing.45,46
Studies have demonstrated accelerated granulation tis-
sue formation when compared to standard wound ther-
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apies.43,47 It appears that the uniform force applied to
the wound bed results in angiogenesis, growth factor
expression, and cell recruitment.
Negative pressure wound therapy has been shown
to rapidly reduce wound volume and may be especially
useful with deep wounds and cavitary wounds since
healing of these requires the development of granula-
6 WOUNDS www.woundsresearch.com
tion tissue to fill the defect before epithelialization can
occur.43,48 The subatmospheric pressure clears wound
exudate as well as microorganisms, thereby reducing
wound edema, bioburden, proinflammatory cytokines,
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and MMPs.43,49,50
Used for both acute and chronic wound manage-
ment, NPWT may assist as a bridge to surgical closure
or to support closure by secondary intention. Studies
have shown decreased wound closure times for a va-
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riety of wounds.51 Negative pressure wound therapy
can reduce the wound bed preparation time prior to
skin grafting44,47,52 and is useful in securing skin grafts
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and reducing graft failures. Debrided wounds respond
to NPWT better than nondebrided wounds. All devital-
ized tissue should be removed to create an acute wound
base. Exposed vital organs, exposed bypass grafts, and
coagulopathy are contradictions to the use of negative
pressure. Any bleeding must be completely controlled
prior to applying the device.44,47,51,52
The standard application pressure for most wounds
is -125 mm Hg in a continuous mode with an effective
range between -40 and -150 mm Hg. Wounds with an
ischemic component may be best managed with de-
creased pressure, while highly exudative wounds ben-
efit from higher negative pressures.53
Cell therapy and cell-containing tissue-engineered
skin represent a significant advance in the treatment of
difficult wounds. The first cell-containing product was
developed and reported in 1979 by Bell, Ivarsson, and
Merrill,54 following Rheinwald and Greens process of
sustaining living cells in tissue culture a few years be-
fore.55 These cell-containing products are beneficial
because they 1) act as a biologic dressing; 2) provide
healthy, responsive cells as opposed to the senescent,
nonresponsive cells commonly seen in chronic wounds;
3) act as a smart material responding to the wound
environment providing the necessary growth factors at
the time needed to stimulate healing; 4) operate as a
source for growth factors commonly known to be miss-
ing in chronic wounds; 5) act as a template for develop-
ing new blood vessels and granulation tissue; and, 6) in
the presence of keratinocytes, act as a source for anti-
bacterial peptides (defensins) that suppress bacteria on
the wound.56
Currently, there are 2 cell-containing tissue engi-
neered skin products with US Food and Drug Adminis-
tration (FDA) approval available for use in the treatment
of wounds. Dermagraft (Shire Regenerative Medicine,
San Diego, CA) is a single cell product containing fibro-
 Gale et al

Table 2. Methods of compression.

Type Example Application Advantages Disadvantages Stiffness
Inelastic Zinc paste (Unna) Trained staff, may High working pres- Messy Very high

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stay for some days sure, well-tolerated
during rest
Short stretch wrap Double short stretch Trained staff, may High working pres- Slipping High
compression bandage stay for some days sure, well-tolerated
(Comprilan, BSN during rest, wash-
Medical-Jobst, Char- able and reusable

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lotte, NC)
Multicomponent Light compression Trained staff, may High working pres- Not reusable High
short stretch bandage (Coban 2 stay for some days sure, well tolerated

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Layer Lite Compression, during rest,
3M Health Care Skin &
Wound Care, St. Paul,
MN)
Multicomponent Multilayer compres- Trained staff, may High working pres- Not reusable, High
long stretch

Long stretch wrap

Elastic
sion bandage (Profore,
Smith and Nephew,
Inc, St. Petersburg, FL)
Elastic bandages (ACE
Brand Sports Medicine
Products, 3M Health
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stay for some days

Easy application,
needs to be removed
over night
sure, well-tolerated
during rest
bulky and warm

Self-application, re- Low working pres-

stricted reusability sure, not tolerated
when applied with
Low
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Care Skin & Wound high pressure
Care, St. Paul, MN)
Compression Variety of products in Self-application Self-management, Low working low
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stockings different compression patient can shower, pressure, Difficult

Elastic classes perform daily skin donning
care
Ulcer stockings Double stockings Basal layer stays Self-management, Difficult donning Medium
(ulcer kits) overnight, keeps ul- patient can shower,
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cer dressing in place, perform daily skin

second stocking care
during day
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Velcro-devices Compression garments Self-application, Self-management, Unappealing ap- Medium-

(short stretch) (Juxta-Lite, Juxta- self-adjustable patient can shower pearance when high
CURES Compression and perform daily compared to stock-
Ulcer Recovery System, skin care ings
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CircAid a medi com-

pany, Whitsett, NC)
Extremity pump Variety of products in Self-application, Self-management, Works when High
different versions self-adjustable patient can shower patient is resting
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and perform daily for limited time,

skin care adjunctive use
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blasts on a polyglactin matrix that is delivered frozen
and has to be thawed before use. Apligraf (Organogen-
esis Inc, Canton, MA) is a bilayered, bicellular product
containing keratinocytes and fibroblasts in a bovine col-
lagen matrix that is delivered ready to use. The FDA has
approved both products for the treatment of diabetic
foot ulcers, and only the second for the treatment of
venous leg ulcers. Both products are derived from hu-
man cells.
It is believed that chronic wounds are often locked
in the inflammatory phase of wound healing and likely
have elevated protease and inflammatory cytokine lev-
els, although there is currently no way to quantitate
this.57-59 This inflammatory microenvironment should be
Vol. 26, No. 1 January 2014 7
 Gale et al
corrected to improve success rates with cell-containing
therapy, or the cells and matrix will be destroyed. This
wound bed preparation can be accomplished by com-
pression therapy in the presence of edema57; topical ap-
plication of a 1% doxycycline cream to reduce wound
proteases31 since there are very few disadvantages to
using doxycycline for the 3 week course of therapy rec-
ommended by Chin and Schultz31; and protease reduc-
ing dressings such as oxidized regenerated cellulose/
collagen/silver32 prior to application of cell product.
Once applied, the cells must be protected to func-
tion to their fullest capacity by avoiding the toxicity
of topical products such as silver dressings, as well as
unnecessary washing and debridement prior to reap-
plication of cells.
Therefore, if a wound has not demonstrated signifi-
cant healing after 4 weeks of good wound care, the ba-
sic tenets of which are incorporated in the DOMINATE
es such as cell therapy. (Keep in mind these products
PL
approach, it is appropriate to consider technical advanc-
are to be used in addition to, and not instead of, standard
wound care.)
U
Furthermore, traditional surgical wound closure pro-
cedures still have an important role in wound care and
can expeditiously help wounds close once the wound
D
bed is properly prepared. Selective primary closure, as
well as skin grafting, continue to be effective and can
significantly reduce wound healing time. Of course there
are cost considerations, as skin substitutes are usually
T
applied at the clinic and may need to be reapplied. So,
hospital and operating room costs need to be weighed
against the costs of using skin substitutes.
O
Acellular therapy/extracellular matrices can also help
heal chronic wounds which often are not only deficient
of healthy, responsive cells, but also have a deficit in ex-
N
tracellular matrix (ECM).60 Wound healing requires scaf-
folding for cells which ECM provides while coordinat-
ing healing.61 Cells without ECM dont do well and an
ECM without cells is not fully functional.62
O
Replacement of ECM in problem wounds can provide
the deficient components and stimulate angiogenesis, fi-
broplasia, and wound closure. An FDA-approved porcine
D
small intestinal submucosa wound matrix (OASIS, Smith
& Nephew, London, UK) has been shown in random-
ized trials to positively affect healing rates in difficult
mixed arterial/venous wounds, diabetic foot ulcers, and
chronic venous leg ulcers.63-65 Human acellular dermal
matrix (Graftjacket, KCI, San Antonio, TX) is approved
for diabetic foot ulcers and has demonstrated improved
8 WOUNDS www.woundsresearch.com
healing rates compared to moist wound therapy66 and
to wound gel in sharply debrided wounds.67 Other ECM
products with unique properties are becoming available
such as a sheet and powdered micromatrix produced
TE
from porcine urinary bladder, which preserves the base-
ment membrane.68,69
Therapeutic angiogenesis stimulates granulation.
Becaplermin (Regranex, Smith and Nephew Inc, St. Pe-
tersburg, FL) is a recombinant human platelet-derived
A
growth factor with biological activity similar to endog-
enous platelet-derived growth factor. It recruits and
stimulates proliferation of wound repair cells including
IC
fibroblasts and vascular smooth muscle cells, enhancing
the formation of granulation tissue. The FDA approved
becaplermin in 1998 for treatment of diabetic foot ul-
cers that extend into the subcutaneous tissue that have
adequate blood supply. Currently, it is the only FDA-ap-
proved growth factor available. When used in conjunc-
tion with standard wound care (ie, DOMINATE), the
gel demonstrated a 43% increase in the incidence of
complete wound closure (P = 0.007) vs placebo, and re-
duced the time to healing by 32%, nearly 6 weeks faster
than placebo.70 There is also evidence in the literature
supporting combination therapy with becaplermin gel
and collagen-containing dressings in patients whose
wounds failed to heal after factors known to adversely
affect healing were addressed.71,72
Initial concerns about topical administration of beca-
plermin gel potentially inducing cancer have not been
substantiated. Systemic absorption is minimal and a
large study of becaplermin with matched comparators
showed no increased cancer risk.73
E-Edema is a common, major component of ve-
nous and lymphatic insufficiency affecting all phases
of wound healing and often associated with leg ulcers.
Venous insufficiency can lead to venous hyperten-
sion with readily recognizable stasis pigmentary skin
changes. Confirmation of suspected venous disease is
best accomplished with duplex ultrasound in accred-
ited vascular laboratories. Discovery of recent throm-
bus may warrant anticoagulation. Reflux, especially as
a result of treatable valvular insufficiency, is important
to document for future considerations, since reduction
of venous hypertension by elimination of incompetent
superficial venous valves can reduce likelihood of recur-
rent ulcerations.74 As demonstrated in meta-analyses and
international recommendations, compression therapy
is the cornerstone in managing patients with leg ede-
ma and venous leg ulcers (Table 2).75,76 An ABI of 0.7

or greater seems adequate to safely allow 30-40 mm Hg
leg compression. With medial sclerosis (eg, diabetes, re-
nal disease, atherosclerosis), distal arteries may become
noncompressible, invalidating the ABI, in which case toe
pressure measurements and waveform analysis should
be employed. If significant arterial insufficiency is also
felt to be present, wound healing should improve with
early correction.
The Unna boot (ie, short-stretch gauze impregnated
with calamine lotion, zinc oxide, and gelatin) with an
outer layer of a self-adherent dressing is often a good
first choice. It can be left in place for a week, provides
excellent, rapid compression that quickly reduces the
edema, is relatively comfortable for patients, and is eco-
nomical. It is often paired with moisture balance and/or
silver-impregnated dressings. The patient remains ambu-
latory while receiving leg compression.
ent, such as swollen feet, squared swollen toes, and
PL
Leg swelling and ulcerations can also be related to
lymphedema. When classic diagnostic features are pres-
dorsal foot pitting, the diagnosis can be clinical. Con-
firmation can be made by lymphatic uptake of radioac-
U
tive tracer injected into the foot (lymphoscintigraphy).
Currently there is significant benefit to be derived from
manual lymphatic drainage and decongestive therapy
D
initiated in a lymphedema clinic and continued at
home. Intermittent pneumatic compression has been
recently shown to be effective in treating venous type
ulcers in patients with chronic lymphedema.77
T
Phlebolymphedema refers to a condition involving
mixed venous and lymphatic insufficiency of the lower
extremities which is probably underrecognized.78 Diag-
O
nosis can be established using clinical criteria together
with lymphoscintigraphy, duplex ultrasound, computed
tomography, magnestic resonance, or contrast venogra-
N
phy and treatment is directed by the cause, either venous,
lymphatic, or both, using minimally invasive procedures.
Conclusion
O
A final and extremely important point to include in
the DOMINATE Wounds concept is E-education. Lack
of patient compliance is often the reason wounds fail
D
to heal. This is especially true in the case of edema
management, wound offloading, and diabetic blood
sugar control. Compression stockings can be burden-
some but are essential, off-loading footware may be
cumbersome but often is absolutely necessary, and
blood sugars consistently above 200 mg represent a
significant impediment to wound healing (C. Attinger,
Gale et al
MD, oral communication, March 2013). Therefore, it
makes sense to prioritize patient education regarding
the DOMINATE concept. If patients understand the
value of the DOMINATE components with respect to
TE
their wounds and receive constant reminders, compli-
ance and healing rates should increase.
As health care systems become subject to increas-
ing oversight, and health care dollars become rationed,
wound centers will need to demonstrate the cost-
A
effectiveness of wound healing as a requirement for
reimbursement. The challenges for such demonstra-
tion include the lack of defined outcomes for treating
IC
uncommon wounds and the absence of guidelines for
managing patient behavioral issues such as compliance,
or mental health conditions. Future research is needed
to address these concerns. In the meantime, having a
practical, standard approach to wound care that is con-
sistent, effective, and supported by evidence can only
help when wound centers are audited.The use of DOMI-
NATE provides such an approach.
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