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Effect of negative pressure wound therapy on
Vacuum-assisted closure (VAC), sometimes referred to as microdeformational wound therapy
(MDWT) or negative pressure wound therapy (NPWT), has revolutionized wound care over the
last 15 years (Fig 1). This monograph describes our current understanding of these technologies,
the questions that remain, and what the future may hold for technologies based on
Dressings to treat complex wounds have traditionally been made of cotton gauze which
could be soaked with a variety of chemicals including normal saline and sodium hypochlorite
solutions. In the 1960s, the importance of keeping the wound moist was discovered and a wide
array of hydrogels, alginates, and other polymeric and biologically based dressings were
developed. More recently, these dressing materials have been combined with antimicrobial
compounds such as silver. Collectively, there are approximately 1500 dressing types available to
be used by clinicians in the United States. Most of these products are used based on clinicians
experience often coupled with in vitro and in vivo experimental work and limited noncontrolled
clinical trials. For the average clinicians, ﬁnding the best dressing for a speciﬁc wound can be a
In contrast, advanced wound care products such as growth factors, bioengineered skin, and
dermal scaffolds are few in number and have more robust clinical data demonstrating their
effectiveness, but they are expensive and can be logistically challenging to use. Generally, these
products are used only after traditional moist-dressing products have failed or for large wounds.
When NPWT was introduced in the United States, there were a series of devices (V.A.C., KCI,
San Antonio, TX) manufactured and marketed by 1 company. Common to these devices was an
open-pore foam to ﬁll the wound cavity, a semiocclusive wound dressing, a suction tubing, and a
suction device. Because there was signiﬁcant wound surface deformation at the foam-wound
interface, we believe that the generic term MDWT helps distinguish this technology from other
NPWT devices that use different interface materials or suction settings. Owing to the early
introduction, most of the mechanistic work and large clinical studies were done using the V.A.C.
devices, and these results do not necessarily apply to all NPWT devices (Figs 1 and 2). It is
important when reviewing the literature to be aware of the speciﬁc device used for either basic
science or clinical application, as the results from a particular device studied may not translate to
all NPWT results.
Contents lists available at ScienceDirect
journal homepage: www.elsevier.com/locate/cpsurg
Current Problems in Surgery
0011-3840/& 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
Current Problems in Surgery 51 (2014) 301–331
When using NPWT devices in mobile areas such as the abdomen, signiﬁcant shrinkage of the
wound can be observed as the wound edges come together by a combination of foam shrinkage
and drawing the edges of the wound together by foam contact. At the wound interface, the foam
creates microdeformations that stretch cells and activate molecular pathways for angiogenesis
and cell division. For wounds with edema, these devices have the capacity to remove a large
amount of ﬂuid. For example, in large open abdominal or fasciotomy wounds, signiﬁcant
quantities of edematous ﬂuid can be removed, resulting in decreased tissue swelling. In addition,
because of the materials used to cover the wound, the dressing acts as an insulator to keep the
wounds warm and moist. In our practice, we use these devices after the wounds are debrided
and are clean of visible necrotic material (Fig 3). They can be used until the wound is closed or
used in preparation for surgical closure such as a skin graft or ﬂap. These devices also have the
advantage in that they often only need to be changed every 2-3 days, reducing the number of
dressing changes for patients. The early clinical results of case reports and small series were
Fig. 1. A visual representation of the deﬁnitions used in this monograph. Negative pressure wound therapy (NPWT) is a
term that refers to any device that applies differential suction (ie, reduced local pressure) to wounds. Microdeforma-
tional wound therapy (MDWT) refers speciﬁcally to NPWT systems that create microdeformations (appearing as
microdomelike structures) at the wound surface. A number of commercially available devices exist within these
deﬁnitions; the vacuum-assisted closure (VAC) therapy systems are some of the most commonly used. (Color version of
ﬁgure is available online.)
Fig. 2. The mechanisms of MDWT. (Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331302
impressive, prompting surgeons to apply this technology to a wide range of clinical problems.
These devices have been commonly used to treat pressure sores, open abdomens, sternal
wounds, traumatic wounds, diabetic foot infections, second-degree burns, and skin graft
recipient sites. They are contraindicated in untreated ﬁstulas, untreated osteomyelitis, or in a
wound with malignant tumor present. Caution should be used when the porous foam is used
around vascular structures such as the heart or large blood vessels because erosion may occur,
resulting in massive blood loss. Caution must also be taken when placing the porous foam in
contact with visceral organs because erosion can occur, leading to ﬁstula. The porous interface
material is highly efﬁcient at removing blood; therefore, appropriate alarms need to be present
on the suction device to avoid exsanguination. Many suction pumps have design features that
allow continuous or intermittent application. The optimal waveform for intermittent application
has not been determined. Although there are basic science studies showing a greater response
using intermittent therapy, this therapy often causes discomfort to patients or can be
bothersome during sleep.
Currently, there is much innovation in the NPWT space. Variations of these therapies have
been used to treat closed incisional wounds, decrease edema, and facilitate healing. Instillation
devices have been designed that allow delivery of a variety of irrigation solutions, including
antibiotics. Finally, changes in the interface material may allow surgeons to customize the
biological response of speciﬁc wounds. For example, pore size appears to be a large determinant
on the rate of granulation tissue formation. NPWT devices can be combined with other surgical
advances such as dermal scaffolds or processed allogeneic or xenogenic materials. We hope that
future research in this area will lead to better wound therapy options for our patients.
Fig. 3. The 4 primary mechanisms of action of MDWT. (Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 303
Pressure is deﬁned as force divided by the area to which it is applied. On earth, we live in a
pressurized atmosphere that allows us to survive. The relationship of pressure and volume can
be approximated using the ideal gas equation: PV ¼ nRT. In this equation, P ¼ pressure, V ¼
volume, n ¼ number of moles of gas, R ¼ the universal gas constant, and T ¼ temperature in
degrees Kelvin. As such, pressure must always be a positive quantity and “negative pressure” is a
misnomer. Gauge pressure, where a pressure is compared with a standard, can be reported as a
At sea level, the air that surrounds us presses on our skin in every direction at 1.0 atm,
760 mm Hg or 101 kilopascals. As we travel to higher altitudes, this pressure decreases. For
example in Denver, Colorado, at approximately 5000 ft above sea level, the barometric pressure
decreases by 125 mm Hg (approximately 635 mm Hg). Similar pressures are maintained in
commercial aircraft at cruising altitudes. In contrast, if we travel to levels below sea level, the
pressure increases. Because water is denser than air, divers and submarines can be exposed to
very high pressures when descending in water. For example, at a depth of just 5.6 ft, the pressure
would increase by 125 mm Hg (or 885 mm Hg). Within our bodies, structural elements maintain
pressure differentials that are responsible for ﬂuid ﬂows. On a macroscopic scale, the rib cage
and diaphragm allow subatmospheric pressure to develop within the thoracic cavity facilitating
air transport into the lung via the tracheobronchial tree. In the cardiovascular system, blood
vessels constrain high pressures from being transmitted into surrounding tissues. On a
microscopic scale, arterioles, capillaries, venules, lymphatic vessels cells, and the extracellular
matrix (ECM) exist in close proximity, yet differential pressures are maintained through
structural elements in the connective tissues. Arterial blood pressures, of the order of
100 mm Hg, provide the necessary driving force for blood to perfuse capillary networks and
arrive in venous systems of 5-10 mm Hg. Lymphatic ﬂuid transudes through the walls of
capillaries and is regulated by osmotic and pressure differentials. Much of this is related to
structural elements in the ECM such as collagen, glycosaminoglycans, and elastin. Accumulation
of ﬂuid within the extracellular space results in edema. Excessive pressure within arterial
systems can result in proliferation of cells within the arterial wall or excessive dilatation of
arteries (aneurysms). Suction devices applied to wound surfaces are commonly applied at values
around 125 mm Hg (Fig 4). The same structural elements in tissues that maintain pressure
differentials in the vascular system also modulate the transfer of suction throughout tissues. The
applied differential suction, as it interacts with the wound surface through the interface material
is critical to activating biological pathways.
Part I—History of negative pressure therapy
The role of the local microenvironment as it responds to mechanical inﬂuences has gained
increasing attention from both clinicians and researchers interested in wound healing. There is a
large class of wound care systems being used today or in the process of being developed that
have been broadly referred to as NPWT devices.1
In particular, systems that apply an interface
material to evenly distribute vacuum to wounds, while causing microdeformations, have been
referred to as MDWT.2
A speciﬁc commercial device that has had a large market penetration and
has been used in most clinical studies to date is referred to as V.A.C., based on the pioneering
work of Argenta and Morykwas3
These novel therapies have been shown to facilitate the healing of various types of wounds
derived from trauma, infection, congenital deformities, and tumors. The surging number of
clinical trials and fundamental studies in this ﬁeld has provided us with a more detailed
understanding of the observed clinical effects as well as the mechanism of action at the tissue,
cellular, and molecular levels.
Suction has been used in medicine for many years. Bier described the use of suction cups for a
variety of ailments that have been largely abandoned.4
Suction is frequently used for many
indications including evacuation of purulence, closed suction drainage of surgical wounds,
removal of gastric ﬂuids, and collapse of the pleural space. Excessive suction can damage tissues,
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331304
and manufacturers have built devices to limit high levels of suction to fragile organs such as the
lung. Typically, these devices have been designed to apply low levels of suction (o40 mm Hg).
Liposuction uses high levels of suction that facilitate tissue removal.
Mechanical forces have been used outside of medicine for centuries to create tissue. Women
in Ethiopia use ceramic plates of increasing diameter to expand the lower lip while some in
Thailand use metal rings to stretch out the neck. The importance of mechanics in repair was
popularized by Julius Wolff (1836-1902), a German surgeon, who recognized that bone
morphology adapts to applied mechanical loads. The pioneering Russian surgeon, Gavriil
Ilizarov, put this principle into practice treating patients in need of bone lengthening. Although
he further developed the science behind this during the 1950s, his work did not become well
known in the United States until the 1980s. His observations led to the ﬁeld of distraction
Fig. 4. Temporal and spatial relationship of wound interstitial pressure. Paradoxically, there is an increase in interstitial
pressure close to the wound. The pressure differentials attenuate over time. Artist representations of the increase in
tissue pressure occurring with MDWT, approximated by the results observed by Kairinos and colleagues, assuming an
application of 125 mm Hg suction pressure (common clinical value). The size of the increase decreases with distance
from the wound surface, dissipating exponentially beyond 1 cm. However, no deﬁnitive data exist to the authors'
knowledge regarding pressure changes within the ﬁrst centimeter of depth below the wound surface. Based on FEA and
the formation of microdeformations at the surface, it would not be surprising for the most superﬁcial tissue to
experience subatmospheric pressures. The magnitude of pressure increases also decrease gradually over the course of
treatment, although tissue pressure may remain elevated even after 48 hours of treatment, compared with the pre-
MDWT baseline. Owing to a dearth of data in sample size and consistency between wound types, this chart merely
depicts the general trends observed. Of the 10 treated wounds studied by Kairinos and colleagues, only 3 were found to
eventually decrease in pressure to below baseline levels during prolonged therapy. (Color version of ﬁgure is available
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 305
osteogenesis. In soft tissue, surgeons recognized the skin's ability to expand during weight gain
or pregnancy, inspiring the development of tissue expanders. In 1957, Neumann5
use of a rubber balloon to expand the skin for the purpose of covering exposed cartilage.
Radovan and Austad both developed tissue expanders in 1975, which led to a new class of
devices that could generate tissue de novo.
As the largest organ in the human body, skin and the underlying subcutaneous tissues are
constantly subjected to both extrinsic and intrinsic mechanical forces. For example, gravity, body
movement, and trauma are extrinsic forces, while blood ﬂow or growth of the skeleton
generates intrinsic forces. Endothelial cells, keratinocytes, and ﬁbroblasts (among others)
respond to these mechanical forces. Given the existence of this cellular mechanosensitivity, the
spatial and temporal responses of skin to mechanical stimulation are current areas of growing
interest in wound management. The increased clinical demand combined with a better
understanding of the skin's mechanotransductive properties has spawned signiﬁcant innovation
in wound healing therapies using mechanical forces.
The interaction of wound healing and mechanical forces is analogous to where forces have
been applied in other areas of the human body. The understanding and application of tensile
forces (eg, stretching) are also related to the pathogenesis and treatment of excessive wound
healing such as hypertrophic scarring or keloid formation. Microdeformation, caused by suction
devices with an interface material, has only been recently recognized as having the capacity of
applying tensile forces to the wound surface. Its application in both acute and chronic wound
management is a nonpharmacologic strategy. Its modulation of the healing process relies on a
class of devices based or engineered on the concept of wound suction. In 1997, Argenta and
ﬁrst described applying controlled suction through open-cell foam to create an
environment conducive to healing and granulation tissue formation.6
This device was one of
several developed by their group that uses suction to treat wounds, which they deﬁned as
NPWT. The forces that resulted from the application of suction differed from the traditional
dressings, such as elastic compression wraps, that often applied a compressive force to
Although a number of device systems have been described, currently, the most popular
clinical systems use open-pore foam dressings, which result in the formation of tiny, domelike
structures at the wound surface that cause microdeformations to the wound surface. Therefore,
we use the term MDWT for devices that deform wounds on the micron-to-millimeter scale,
incurring morphologic and functional changes in cells that further improve wound healing.7
an aside, the application of MDWT actually generates a seemingly paradoxical increase in
pressure below the wound surface, reinforcing MDWT as the clearest deﬁnition for such
The VAC system
The VAC system is a relatively new technology in wound management. The general system is
made up of 4 major components: (1) a ﬁller material or sponge placed into the wound; (2) a
semipermeable dressing to isolate the wound environment and allow the vacuum system to
transmit subatmospheric pressures to the wound surface; (3) a connecting tube; (4) and a
vacuum system (Fig 3). A ﬂuid collection canister is also incorporated with the device. As a
precautionary measure, an alarm sounds if the canister is full, alerting clinicians to potential
The structure of the material packed into the wound may be important in the efﬁcacy of
NPWT. Although different materials may be used with various NPWT devices, reticulated,
open-pore foam is the most common. This foam is made of many cells or bubbles that
are highly interconnected. This structure, as the name suggests, resembles a 3-dimensional
net, which is in the form of a lattice of open-faced polyhedra. Importantly, this attribute
permits the vacuum to be distributed evenly throughout the foam and improves ﬂuid
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331306
As part of the commercial VAC system, 3 general types of foam are available: black
polyurethane ether (V.A.C. GranuFoam, KCI), black polyurethane ester (V.A.C. VeraFlow, KCI), and
white polyvinyl alcohol (V.A.C. WhiteFoam, KCI). Other types of foams are available in other
commercial devices and other types of interface materials continue to be developed. The
traditional polyurethane ether foam is hydrophobic, whereas the polyvinyl alcohol and
polyurethane ester foams are more hydrophilic. The polyurethane ester devices are designed
for use with instillation therapy. Clinicians have often used the traditional polyurethane ether
foams for wounds with large ﬂuid drainage and for stimulating granulation tissue formation. In
contrast, the polyvinyl alcohol sponges have been used in cases where the wound tunnels or
when delicate underlying structures, such as tendons or blood vessels, need to be protected.
Finally, the increased density and smaller pores of the WhiteFoam help to restrict ingrowth of
granulation tissue, thereby diminishing pain associated with dressing changes and reducing risk
when hypergranulation is a concern.10,11
NPWT therapy is most commonly applied to an open wound, accelerating the healing process
and bringing the wound margins closer together. Other uses, methods of application, and
different patient conditions have been discussed at greater length in the section Clinical
applications of NPWT, following an explanation of the mechanisms of action. Overall, the
healing of both acute and chronic wounds is improved through the combination of components
that include the wound-foam interface, semiocclusive microenvironment, and the mechanical
forces incorporated into NPWT.
Part II—Mechanisms of action
The events underlying the improvement in wound healing observed with MDWT can be
broadly classiﬁed as primary mechanisms and their associated secondary effects. Overall, 4
primary mechanisms of action have been proposed: (1) wound shrinkage or macrodeformation;
(2) microdeformation at the foam-wound surface interface; (3) ﬂuid removal; and (4) stabiliza-
tion of the wound environment (Figs 2 and 3).12
There are also several secondary effects likely
involved in mechanotransduction pathways that alter the biology of wound healing including
angiogenesis, neurogenesis, granulation tissue formation, cellular proliferation, differentiation,
Macrodeformation refers to induced wound shrinkage caused by collapse of the pores and
centripetal forces exerted onto the wound surface by the foam. Polyurethane ether foams
exposed to 125 mm Hg suction can decrease the foam volume by approximately 80%13
in a substantial decrease in wound surface area in a porcine model.14
The extent of contraction is
largely dependent on the deformability of the wound. The baseline tension in skin causes wound
margins to naturally pull apart. Because of the inherent tension of the dermis and variable
attachment to underlying structures, different wounds contract to different degrees. For
example, the low elasticity of scalp skin over the rigid calvarium is likely to contract less than a
large abdominal wound in an obese patient.
Interestingly, in both in vivo and in vitro studies, a seemingly paradoxical increase in
extracellular pressure is observed in the tissue underlying the wound bed, presumably due to
tissue compression induced by macrodeformation.8,15
Such a phenomenon may seem more
obvious with circumferential NPWT dressings, for example, in treating large degloving injuries
encompassing a limb. As suction is applied, air is evacuated from the foam and its reduction in
volume results in the compression of underlying tissue. Increased tissue pressure is also observed
when NPWT is applied to more cavitary wounds, where the top of the foam is virtually at level
with the surrounding skin. Logically, one might assume that negative gauge pressures would
translate to lower pressure in adjacent tissues. However, pressure in the underlying tissue
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 307
increases with elevated suction. These extracellular pressure changes also vary with distance from
the foam-wound interface and the time of treatment (Fig 4).8
Taking these ﬁndings into
consideration can reduce the risks of NPWT in patients with compromised perfusion, potentially
contraindicating this treatment, especially if circumferential dressings or higher suction pressures
are to be used. Overall, the effects of macrodeformation depend on the type of tissue treated,12
level of suction,14
the volume of the foam,16
the pore volume fraction of the ﬁller material
(proportion of sponge occupied by air),17
and the deformability of the surrounding tissues.12
Microdeformation refers to the undulated wound surface induced by the porous interface
material when exposed to suction. These physical changes occur on the micron-to-millimeter
scale, given common pore diameters are in the range of 400-600 μm, and set in motion a host of
other effects that aid in the healing process. To better understand the micromechanical changes
involved, models have been designed to mimic tissue stretched by a combination of suction and
a counteracting downward force by the sponge struts. In computer simulations of this interface
with ﬁnite element analysis (FEA), our model indicates that at 110 mm Hg, MDWT application
using typical foam pore sizes causes an average tissue strain of 5%-20% over most of the wound
surface. Quantitatively, tissue strain corresponds to the percentage increase or decrease in
length of a given material subjected to external forces.18
These mechanical forces appear to be transmitted to individual cells via the ECM. In MDWT,
cells are subjected to a variety of mechanical forces, including shear and hydrostatic pressure
from extracellular ﬂuid, stretch and compression from their surrounding matrix, and the
ubiquitous pull of gravity.12
These mechanical forces, particularly microstrain, are also highly
variable across the wound surface (albeit in a repeating pattern between sponge pores). FEA has
demonstrated that tissue immediately below the foam struts experiences compression, whereas
tension is found along the wound surface centrally in the pore.18
Overall, the regular yet highly
variable microenvironment created during this therapy is what causes microdeformation.
Microdeformation, in essence, is the morphologic result of these integrated mechanics. Cell
shape has been demonstrated to be a determinant of cellular function.19
In addition, cells are
known to adapt to physical stresses.20
Therefore, changes in cellular functions can be initiated by
these dynamic physical inputs. This concept has been discussed in greater detail in the
secondary effects of NPWT action.
Fluids in the body have been classically divided among 3 compartments: (1) intravascular,
(2) intracellular, and (3) extracellular. Fluid transport between these compartments is primarily
governed by the Starling equation, which takes into account the hydrostatic and osmotic
pressure differentials across semipermeable membranes. The most variable of these compart-
ments is the extracellular space. Excess ﬂuid in this compartment is commonly seen as edema,
whereas a lack of ﬂuid in this compartment is a sign of dehydration. The extracellular ﬂuid
compartment is drained by lymphatics, the disruption of which can lead to lymphedema.
Depending on the underlying pathology, chronic wounds and edema are often concomitant,
as is the case with lower extremity diabetic ulcers. Excess ﬂuid buildup is commonly accepted as
a contravening factor in healing, partly owing to the compressive effect it can exert on local cells
and tissues. Individual cells generate intrinsic tension via their cytoskeleton and interactions
with the ECM, inducing a proliferative response.12
Elevated ﬂuid pressures in the interstitium
diminish this response by dampening intrinsic tension buildup. Fluids from the extracellular
space appear to communicate with the wound surface. Applying vacuum to this surface results
in ﬂuid removal from many wounds, including the extracellular space. In our experience,
particularly in fasciotomy wounds or in open abdominal wounds, large amounts of ﬂuid can be
Fluid removal likely reduces compression of the microvasculature, optimizing tissue
perfusion by reducing difference and potentially allowing increased blood ﬂow to the area
The polyurethane drape is semipermeable, allowing a small amount of air to enter the
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331308
system, thereby preventing a ﬂuid lock and allowing continuous evacuation of ﬂuid. NPWT also
likely reduces the amount of ﬂuids that must be cleared through the lymphatic system. Toxins
from the wound, bacteria, and exudate can also be removed with the ﬂuids.7
MDWT also inﬂuences ﬂuid removal more indirectly. The associated microdeformation
enhances ﬂuid drainage, ultimately reducing tissue edema, by generating an increased pressure
gradient between the interstitial space and the interface material.7
This compression might also
be a mechanism for increased lymphatic drainage from the wound. In addition, MDWT induces a
gradual increase in lymphatic density at wound edges, thereby improving drainage (Fig 6).23
Alteration of the wound environment
Fluid removal is an important element in achieving a wound environment conducive to
healing. Complete evacuation of ﬂuid with its accompanying electrolytes and proteins does, in
theory, also stabilize osmotic and oncotic gradients at the wound surface.12
The foam material
and semiocclusive drape act as thermal insulators to maintain wound warmth.24
Fig. 6. Lymphatic density increases gradually at wound edges during the course of treatment. (Color version of ﬁgure is
Fig. 5. MDWT helps to remove excess extracellular ﬂuid, reducing hydrostatic compression at the capillaries and
reducing the required diffusion distance. The net result is optimized tissue perfusion, aiding in the healing process.
(Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 309
semiocclusive polyurethane drape is fundamental in maintaining subatmospheric pressures at
the wound bed and prevents evaporative water losses. The dressing is impermeable to proteins
and microorganisms, signiﬁcantly reducing the risk of wound contamination. In addition, the
drape exhibits limited permeability to water vapor and other gases, helping to maintain a stable,
moist wound environment.24-26
Different types of NPWT can also optimize the wound environment to address speciﬁc
aspects of the healing process. Instillation of bioactive factors27
and using foam bound with
are 2 common examples of how the wound interface may be altered. These
methods for enhancing the wound environment and possibly improving patient outcomes, have
been discussed in greater detail in a later section devoted speciﬁcally to clinical applications. In
general, NPWT devices assist in wound healing partly because of control of wound ﬂuids while
maintaining a warm and moist microenvironment. In comparison with conventional therapies,
the reduced number of required dressing changes in NPWT also can add to patient comfort.
Wound healing is most often described in terms of 4 overlapping phases: hemostasis,
inﬂammation, proliferation, and remodeling. An alternative model divides the process into early
and cellular phases, offering clearer delineation between processes involved in wound healing.29
The early phase is immediately initiated by tissue injury and largely involves the hemostatic
response and ensuing biochemical changes that set the inﬂammatory processes in motion. The
cellular phase encompasses the ensuing inﬂammatory response, rapid proliferation, differ-
entiation and granulation tissue formation, and ﬁnally, re-epithelialization and scar formation.
These classiﬁcations of wound repair mechanisms offer a suitable context to discuss current
knowledge of the secondary effects of NPWT.
The efﬁcient open-pore foams require that hemostasis is nearly complete before application
of suction, using caution in patients with coagulopatihies. Suction devices should have overﬂow
alarms to alert clinicians when there is excessive blood loss.
Modulation of inﬂammation
During the inﬂammation phase, MDWT removes inﬁltrating leukocytes while simultaneously
inducing inﬂammation. These ﬁndings are supported by the evidence of increased wound
exudate cellularity (particularly leukocytes and erythrocytes) and increased gene expression of
leukocyte chemoattractants, such as IL-8 and CXCL5, in wounds treated with NPWT.30
Cellular responses—division, migration, and differentiation
MDWT generates a complex mechanical environment at the wound surface. The resultant
cell deformations lead to altered function in cellular proliferation, migration, and differentiation.
Cell shape has been well established to govern its behavior31
; the alteration of the cytoskeleton
generates organizational guidance cues for cells (Fig 7).32
For example, cell sensitivity to soluble
mitogens is enhanced with increasing distortion.33,34
Thus, the cellular deformation and
associated cell stretch caused by MDWT induce cell proliferation, thereby promoting wound
healing. This is supported by evidence that short (6 hours) intermittent applications of MDWT to
a diabetic mouse model caused an extended proliferative cell response with increased
expression of Ki-67, a marker for cell proliferation.35
It is also worth noting that the tissue
strain induced by MDWT (5%-20% increase in length) is the same level of strain needed to
promote cellular proliferation in vitro.18
Huang and Ingber36
demonstrated the need for cells to experience isometric tension in order
to provide the mechanical context necessary for cellular proliferation. Growth factors and cell
attachment to ECM proteins were discovered to be essential yet insufﬁcient stimulation in the
absence cellular isometric tension. Chronic wound beds may lack the stable, structural
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331310
scaffolding required for cell extension and adherence, thereby preventing the development of
isometric tension within the cell. This leads to spherization and eventually apoptosis. However,
the suction forces generated by MDWT can elicit an array of mechanical forces within the
tissues, thus allowing cells to proliferate in response to other mechanical and chemical
In addition to promoting cellular proliferation, tissue treated with MDWT exhibits a host of
other characteristics: increased epithelial cell migration, as evidenced by gene ontology
; increased endothelial migration, analyzed in histologic penetration
or endothelial ingress38
; and increased dermal ﬁbroblast migration, indicated by
Resident skin mesenchymal cells and circulating progenitor cells have also
been observed migrating into granulation tissue because of MDWT application.40
epithelial cell proliferation and migration increase, their differentiation during MDWT has been
shown to decrease.30
MDWT inhibits keratinocyte differentiation, as supported by evidence of
downregulated keratin genes (eg, KRT1, 2, 10, 13, and 15) and major corniﬁed envelope genes
(eg, annexin A9, ﬁlaggrin, and loricrin).30
Changes elicited in the wound tissue matrix by MDWT
may inﬂuence differentiation, given that mesenchymal stem cell lineages are highly speciﬁc to
the mechanical characteristics of the ECM. In these cells, soft, stiffer, and rigid matrices guide
differentiation down the paths of neurogenesis, myogenesis, and osteogenesis, respectively.41
The overall interpretation of various studies is that MDWT can promote healing by modulating
inﬂammation and cell migration, while inhibiting epidermal development and maturation.30
Wound-site angiogenesis is mechanically initiated through microdeformation, which
establishes hypoxia and a subsequent vascular endothelial growth factor (VEGF) gradient that
drives the directionalized blood vessel growth (Figs 8 and 9).42
It has been suggested that the
temporary reduction of blood ﬂow at the wound edge15,43
stimulates angiogenesis through the
Fig. 7. Representation of wound bed ﬁbroblast requirement for a trifecta of growth factors, extracellular matrix protein
binding, and isometric tension to undergo proliferation and differentiation. In wound beds, ECM destabilization
precludes buildup of isometric tension, eventually resulting in cell death. This can be compensated by the mechanical
microenvironment generated during microdeformational wound therapy (MDWT). The particular cellular response is
also correlated with the amount of tension the cell experiences: proliferation requires greater stretch than
differentiation. (Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 311
hypoxia-inducible factor-1α–VEGF pathway; tissue hypoxia instigates the upregulation of
hypoxia-inducible factor-1α, which in turn stimulates VEGF expression.42
It is not surprising that
MDWT demonstrates increased microvessel density during chronic wound treatment.44
studies using intermittent MDWT achieved similar results of angiogenic response stimulation.38
Granulation tissue formation
The result of endothelial cell and ﬁbroblast ingrowth at the wound surface, that is,
granulation tissue, which also includes the ancillary ECM and migratory macrophages,
represents a specialized stroma designated for repair (Fig 7). In the proliferation phase, effects
of MDWT include robust tissue granulation, cell proliferation, and blood vessel sprouting. Early
and continuous activation by mast cells is a necessary component of these processes, which are
absent in mast cell–deﬁcient mice.45
Similarly, collagen maturation exhibits strict mast cell
dependence in the proliferation and remodeling phases. However, collagen production does not
share this dependence. Both the production and maturation of collagen are accelerated by
MDWT, but in mast cell–deﬁcient mice, only production increased.45
Mechanotransduction, the process by which cells transduce mechanical forces into biological
signals (eg, altered intracellular environment or gene expression), is integral to the mechanisms
underlying MDWT in that it allows cells to respond directly to applied pressure differentials.46,47
Mechanotransduction signaling in connective tissue has been thoroughly studied in ﬁbropro-
liferative disorders; research has focused primarily on the regulation of cell-ECM interactions
through a variety of signals such as transforming growth factor-β (TGF-β)-Smad, mitogen-
activated protein kinase (MAPK), RhoA-ROCK, Wnt-β-catenin, and tumor necrosis factor-α/
nuclear factor kappa-light-chain enhancer of activated B cell (TNF-α/NF-κB).48
On the contrary,
mechanotransduction research in MDWT is a relatively new area of study. Currently, hypoxia
pathway molecules such as nitric oxide are thought to be involved.9
Fig. 8. MDWT stimulates wound-site angiogenesis through a number of mechanisms: mechanical stimulation
(microdeformation), removal of factors inhibiting angiogenesis, and upregulating proangiogenic factors. Blood vessel
dilation is also observed. (Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331312
Given the complexity of the mechanical environment generated at the wound bed during
MDWT, much of our current data result from in vitro studies (Fig 10). Tissue engineering
bioreactors are commonly used to simulate the in vivo micromechanical environment as well as
the foam-wound interface. Wilkes and colleagues developed a novel 3-dimensional bioreactor to
best mimic the wound bed environment as well as the applied commercially available dressings.
With this device, they subjected tissue analogues to topical NPWT. Following a 48-hour
incubation period, ﬁbroblast cell bodies were observed to have thickened from their initial
elongate bipolar morphology. Dense actin cortical structures were also observed following
Using a 3-dimensional ﬁbrin matrix, McNulty and colleagues39
MDWT inﬂuences ﬁbroblast energetics: energy charge, adenosine triphosphate–adenosine
diphosphate ratio, and cytochrome c oxidase levels were shown to increase. Importantly, they
also discerned that the observed increase in energy status was geared toward biosynthetic
processes associated with healing; levels of the growth factors TGF-β and platelet-derived
growth factors α and β were also shown to increase with the combined application of
subatmospheric pressure and a reticulated open-cell foam. Both are important in granulation
tissue formation as they upregulate collagen production, but platelet-derived growth factors α
and β also upregulate glycosaminoglycans and ﬁbronectin synthesis in ﬁbroblasts.39
In our own
study, it was found that 48 hours after exposure to a suction or foam or perfusion bioreactor,
cells exhibited an upregulation of ﬁbroblast growth factor, TGF-β1, Type I collagen α1, and
smooth muscle actin α2 messenger RNA expression.40
Peripheral nerve response
Younan and colleagues demonstrated that MDWT also activates the neurocutaneous system,
thereby stimulating neural growth and neuropeptide expression. Upregulated peptides include
substance P, calcitonin gene–related peptide, and neurotrophin nerve growth factor (Fig 11). The
Fig. 9. Summary of events that contribute to directionalized angiogenesis. (1) MDWT results in increased pressure in
tissue below the wound surface, leading to the compression of small blood vessels. (2) Localized decreases in perfusion
generate a hypoxia gradient in the wound tissue. (3) Upregulation of hypoxia-inducible growth factor-1α (HIF-1α), which
in turn increases vascular endothelial growth factor (VEGF) production. The resulting growth factor concentration
gradient (4) stimulates directionalized vessel sprouting. (Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 313
Fig. 11. MDWT promotes neural growth and neuropeptide expression (substance P, calcitonin gene–related peptide, and
neurotrophin nerve growth factor). Transient elevations of plasma epinephrine and norepinephrine have also been
observed. (Color version of ﬁgure is available online.)
Fig. 10. Morphologic and biochemical changes of ﬁbroblasts subjected to NPWT. Fusiform cell bodies have been
observed to increase in thickness along with the density of actin cortical structures. Microdeformational wound therapy
(MDWT) also affects cellular energy status, fueling cellular processes associated with wound healing. ATP, adenosine
triphosphate. (Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331314
extent to which this occurs is correlated with the amount of microdeformation, and intermittent
MDWT was shown to have a more pronounced effect than continuous suction.50
MDWT has been shown to elicit transient elevations of plasma epinephrine and norepinephrine,
followed by a slow but long-lasting increase in substance P and neuropeptide Y.51
neuropeptides are recognized as key homeostatic factors in the skin and their secretion may play
a role in the secondary mechanism of MDWT.7,52
Alterations in bioburden
The inﬂuence of NPWT on bacterial load remains controversial. The ﬁndings are conﬂicted
regarding the effect of NPWT on bacterial burden. Some studies have shown a decrease in
bacterial load in response to NPWT.6,53
Others have indicated comparable levels between
treatment and control groups, comparing foam dressings in the presence and absence of suction,
respectively. However, this result was in the context of an in vitro analysis using nonviable
tissue, focusing predominantly on the relationship between bacteria and suction force.54
suggests that any observation of decreased bacterial load results from more than just pure
physical suction. In contrast, another study observed a decrease in the number of non-
fermentative gram-negative bacilli, whereas the level of Staphylococcus aureus increased.55
effect of NPWT on bacterial load remains an area to further explore, particularly in terms of the
variety of responses that may be elicited by different strains. High bacterial counts have been
measured in sonicated foams.56
A very high polymicrobial bacterial load was found in all foams
studied. Porous polyurethane ether foam on high suction (125 mm Hg) had fewer bacteria than
polyvinyl alcohol foams on lower suction.
Part III—Clinical applications of NPWT
NPWT has been applied to a wide variety of wounds varying in location, complexity, and
underlying pathology. It alters the traditional phases of wound healing (Fig 12) and is used in a
variety of anatomical sites throughout the body (Fig 13). The original application of suction to
wounds seems to be a very simple concept. However, the determination of the optimal mode of
NPWT for a speciﬁc wound eludes us. The following sections review the several wound types
that have been studied.
Basic applications of NPWT
Classically, NPWT has been used in the context of open wound management; the interface
foam is applied directly to the wound bed, which is visible at the body surface. Given the effect
that pressure differentials can exert at the wound bed, poorly healing ulcers are common targets
for treatment. Ulcers derived from pressure necrosis, diabetes, and venous or arterial
pathologies can often beneﬁt from NPWT. In the treatment of pressure ulcers, serial randomized
controlled trials (RCTs) demonstrated a reduction in wound surface area,55
volume and depth,57
improved granulation, and a reduced frequency of hospitalization in patients undergoing
This therapy can be an option for managing nonhealing deep-pressure ulcers covered
by soft necrotic tissue; wounds treated with NPWT often show a rapid formation of granulation
In a retrospective cohort study evaluating chronic diabetic, arterial, and venous ulcers
in high-risk patients, treatment with NPWT was shown to increase the incidence of closure (by a
factor of 3.3, 2.3, and 6.3, respectively). Earlier application of NPWT to these wounds also results
in faster healing times.60
In the treatment of diabetic foot ulcers, NPWT promotes wound area
reduction, wound bed granulation, and microbial clearance,61
thereby enabling a higher rate of
limb salvage, especially in Wagner grade 3 and grade 4 ulcers.62
NPWT prevents digit
amputation in the nonoperative management of scleroderma ulcers.63
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 315
The effects of NPWT are both location and disease speciﬁc. NPWT should be applied in
conjunction with treatment of other comorbid diseases such as diabetes, hypertension
peripheral vascular disease, and venous stasis disease. Zutt and colleagues64
importance of concurrent medical treatment of vasculitis and pyoderma gangrenosum along
with adequate debridement and application of NPWT.
Surgical wounds are usually treated with NPWT, often as a bridge to closure with a skin graft
or ﬂap, or secondary closure with NPWT (Fig 14). For example, following melanoma excision, the
application of NPWT provides functional and cosmetic outcomes that include improved
vascularity and reduced scar height.65
Similarly, postoperative NPWT for lymphangioma in
children has demonstrated its effectiveness in decreasing the risk of recurrence and infection.66
Fig. 12. Inﬂuence of NPWT and MDWT on the 4 stages of healing. (1) Although contraindicated in cases of bleeding,
MDWT does generate pressure in the tissue underlying the wound bed, which can compress small blood vessels.
(2) NPWT modulates inﬂammation at the wound bed, while the vacuum pulls out inﬁltrating leukocytes along with
wound exudates. (3) MDWT stimulates cellular proliferation, angiogenesis, and the formation of granulation tissue
during the proliferative phase of healing. These processes are stimulated by mast cells, as is the maturation (not
production) of collagen during the remodeling phase. (4) MDWT increases both collagen production and maturation.
(Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331316
Skin graft and dermal scaffold recipient site preparation
NPWT is commonly used for recipient site preparation for both skin grafts and dermal
scaffolds. Autologous skin grafting is commonly a rapid method to surgically close large wounds
that have granulation tissue that spans the wound. In wounds with small areas of exposed bone
or tendon, dermal scaffolds can often be an effective strategy to produce a complete vascularized
wound bed before skin grafting.67,68
The combination of NPWT with dermal scaffolds provides
excellent immobilization and contact between the scaffold and wound surface.
A multicenter RCT demonstrated related long-term effects when combining dermal scaffolds
(Matriderm, Dr Suwelack Skin & Health Care AG, Billerbeck, Germany) with NPWT; scars were
observed to have greater elasticity and more natural skin pigmentation 12 months post-
operatively, while the rate of postoperative wound contamination decreased.69
Combination therapy—incorporating bioactive factors in NPWT
There have been several novel approaches to NPWT, which have been recently developed.
Antimicrobial silver in NPWT
Traditional NPWT uses polyurethane ether foam; however, its effect on bacteria in the wound
has been inconsistent. To attempt to reduce the amount of bacteria in the wound, silver has been
added to the coating of the foam. Silver has been added to many wound dressings and has been
Fig. 13. Potential targets for NPWT. SSG, split-thickness skin graft. (Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 317
popular as a treatment for burns.70
Stinner and colleagues investigated this potential therapy by
simulating proximal leg wound infections in a goat model; silver dressings were placed beneath
negative pressure dressings in complex orthopedic wounds inoculated with bacteria. The
authors observed a decline in bacterial load (particularly S. aureus) with this treatment
compared with standard MDWT.71
A step further in addressing issues of infection is to modify
the foam itself by impregnating the MDWT foam with silver, additional antimicrobial beneﬁts
can be conferred. This technique has been used successfully in wound bed preparation for
substantial split-thickness skin grafts (STSGs) in the treatment of recalcitrant venous stasis
Instillation therapy provides a methodology to intermittently add ﬂuid to the wound through
either the same or a different port on the NWPT connecting tubing (Fig 15). It is possible to instill
normal saline or other agents to help wound healing such as antimicrobial agents. This has been
demonstrated in the sterilization of massive venous stasis wounds before STSG. The authors
administered dilute Dakin solution (sodium hypochlorate) for a short period after intermittent
cycles of growth-stimulating MDWT. This single-delivery-instill system engineered a unique
wound environment that appeared to maximize wound bed preparation.72
instillation MDWT is another variation with a second port being connected to a continuous-
drip system. Insulin in continuous-instillation MDWT successfully achieves a decrease in time to
Other bioactive factors suggested by Scimeca and colleagues,73
which may be
introduced through the continuous-instillation system include doxycycline, dilute Betadine,
Fig. 14. A 69-year-old woman with a history of endometrial carcinoma with metastases to the right hip, after
hemipelvectomy complicated by complete wound dehiscence: (A) open wound 28 cm Â 17 cm; (B and C) buttock was
pulled up and held together and foam was placed into the remaining open area; (D) 1 month postoperatively; (E) 2
months postoperatively; and (F) 3 months postoperatively. (Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331318
lactoferrin, and phenytoin. Carefully controlled clinical trials will be needed to better
demonstrate the efﬁcacy of this concept.27
Other potential adjuvants
Several other possible NPWT methods have been proposed including the use of platelet gel.
In the case of a nonhealing ileocutaneous ﬁstula, platelet gel was added to the wound bed after
initial NPWT-induced granulation tissue formation. NPWT was then continued, eventually
leading to deﬁnitive surgical repair.74
Adjunctive administration of activated protein C, an
anticoagulant, has also generated positive results where even long-term standard NPWT has
failed. In their pilot study, Wijewardena and colleagues administered activated protein C
injections into the beds of recalcitrant orthopedic wounds. The authors subsequently observed a
successful reduction in wound area and depth, accompanied by signiﬁcant granulation tissue
formation, within only the ﬁrst week of treatment. Patient tolerance of this treatment regimen
was also satisfactory.75
Arginine-rich dietary supplements have also been studied as a
nutritional complement to NPWT. This is a subject of interest owing to its potential for
improving local circulation at the wound bed. Results indicated that infection-induced wound
dehiscence had resolved with complete healing within the ﬁrst month of treatment, with no
evidence of recurrence at 6-month follow-up.76
Other adjuncts, such as Manuka and
Leptospermum honeys, have been used in the treatment of an abdominal phlegmonous lesion
and a nonhealing postsurgical wound, respectively.77,78
NPWT in the treatment of deep infected wounds
Many clinicians have applied NPWT to deep wounds, a situation that has also been studied in
a porcine model. Soft tissue blast injuries were simulated in pigs to more thoroughly observe
changes in bacterial load following NPWT. Compared with traditional gauze dressings, this study
showed that NPWT decreased the bacterial load, blocked infection-induced tissue necrosis, and
resulted in earlier initiation of granulation tissue formation.79
Fig. 15. Instillation VAC. (Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 319
In humans, NPWT has generally been shown to be effective in the control of wound
infections. This is particularly true of thoracic and abdominal injuries, and deep wounds, where
infection management is paramount in treatment. Although often useful, dressings infused with
silver are not always indicated80
or even necessary with NPWT. NPWT systems are able to isolate
wounds from the external environment with a drainage system that may be superior to standard
NPWT in cases of exposed bone or joints or both
Recently, open fractures, particularly of the lower extremity, are frequently being treated
with NPWT systems. These systems keep the wound clean from external contamination and
keep it moist and warm. In their retrospective cohort study of open tibial fractures, Blum and
colleagues compared the rate of deep infection between NPWT and conventional dressing
treatment groups (8.4% and 20.6%, respectively). There was nearly 80% reduction in the risk of
deep tissue infection after adjustment for multivariate analysis.81
Similarly, in a patient with left
knee-joint exposure, the large soft tissue defect was managed by a 20-day course of NPWT.
Despite the original severe wound infection (following open reduction and internal ﬁxation of a
patellar fracture), a granulated wound bed fully covering the exposed bones and joint was
observed after negative pressure treatment.82
NPWT systems are sometimes used as an alternative treatment for lower-extremity wounds
with exposed bones or joints or both when free-ﬂap transfer is contraindicated.82,83
help to reduce both the need for ﬂap transfer and the size of the ﬂap, as demonstrated in type
IIIB open tibial fracture treatment. However, it is worth noting that the authors discouraged the
application of negative pressure for a period lasting longer than 7 days owing to the signiﬁcantly
higher rate of infection and the associated risk of amputation.84
Deep sternal wound infection
Deep sternal wound infection (DSWI), also known as mediastinitis, is a devastating
complication of open heart surgery posing severe risks to patients postoperatively. Without
prompt treatment, the mortality rate from this condition can exceed 50%. Traditional packing of
sternal wounds often resulted in massive bleeding or chronic draining sinus tracts. In a study
cohort of patients with DSWIs, NPWT reduced the risk of early reinfections when used as the
ﬁrst line of therapy. The data were also suggestive of a decrease in the incidence of late chronic
sternal infections and mortality.85
Furthermore, meta-analysis assessing the effect of NPWT on
sternal infections found the length of hospital stay to decrease by 1 week.86
In the case of
methicillin-resistant postcardiotomy DSWIs, MDWT shortened healing time and hospital stay
and lowered the recurrence of infection relative to closed mediastinal irrigation with
Similar to DSWI, poststernotomy osteomyelitis remains a huge concern for patient morbidity,
prolonging recovery time, and necessitating surgical reinterventions.88
NPWT does not
substitute for adequate debridement and antibiotic therapy when osteomyelitis is present.89,90
NPWT as an augmented surgical drain
Deep wound infections can often be associated with the buildup of ﬂuid, either in natural
anatomical cavities or in pathologic abscesses. NPWT offers an improved modality for draining
these infections, partly by providing a greater suction distribution over a larger surface area than
conventional drainage methods. This was shown to help prevent the accumulation of purulent
material in the case of a deep neck abscess involving the mediastinum, thereby avoiding the
need for open thoracotomy.91
Similarly, for postoperative or recurrent pleural empyema, NPWT
used in conjunction with open window thoracostomy can help control sepsis, rapidly eradicating
the local infection in most cases. In addition, NPWT therapy has also been used in complex chest
wall wounds that facilitated improved lung expansion and eliminated empyema recurrence.92
Deep cavitary defects, particularly those derived from high-velocity projectiles or blast
injuries, have also appeared to have beneﬁtted from NPWT. These wounds are unique in that the
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331320
visible superﬁcial tissue defect is often relatively small compared with the underlying injury.
NPWT has been combined with conventional draining methods to achieve an optimized therapy
for such injuries. In their practice, Rispoli and colleagues connected surgical drains to the base of
superﬁcial foam dressings (Fig 16), modifying standard NPWT to convert deep cavitary defects
into superﬁcial ones. This generated suction deep in the wound cavity, reducing dead space and
edema, thereby reducing the risk of infection. Compared with conventional methods, this
allowed the surgeons to minimize further tissue damage to facilitate draining and reduced the
risk of deeper cavities closing off, which can occur with traditional VAC therapy.93
The nature of deep intra-abdominal wound infections has made them another potential
target for NPWT. A number of such techniques have been documented in medical literature. As a
basic principle, NPWT can be used in the abdominal cavity in a manner similar to its use in
treating DSWIs. For example, NPWT has been applied following classical laparotomy and
necrosectomy for acute necrotizing pancreatitis; the foam dressing placed in the opening
created during lesser sac marsupialization (Fig 17). This combination of therapies provided a
number of advantages; importantly, improving patient outcome by accelerating abdominal
closure (open abdomen associated with increased morbidity and mortality). Other beneﬁts
included prevention of abdominal compartment syndrome, improved examination of wound
secretions, and simpliﬁcation of care.94
Other novel approaches to NPWT have been described
including the endoscopic placement of a NPWT device to treat anterior rectal wall anastomotic
NPWT and congenital deformities
NPWT also may provide an alternative to the management of congenital deformities such as
and giant omphalocele.97
The Food and Drug Administration (FDA)
Fig. 16. NPWT use in deep wound drainage. The fenestrated end of a surgical drain is inserted into a superﬁcial foam
dressing, reducing the risk of deep cavity foam adherence without necessitating an increase in superﬁcial wound size.
(Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 321
states that: “The safety and effectiveness of NPWT systems in newborns, infants and children has
not been established at this time and currently, there are no NPWT systems cleared for use in
Variations of the traditional NPWT systems
Closed surgical incisions
Recent in vivo and in vitro studies provide some evidence for the use of NPWT in high-risk
surgical incisions that are closed primarily, to reduce complications of wound dehiscence,
infection, hematoma, and seromas. Preclinical studies have supported this hypothesis, with an
in vivo porcine model demonstrating reduced hematoma and seroma levels in clean, closed
In a prospective randomized multicenter clinical trial, NPWT applied to
closed incisions reduced the relative risk of developing an infection, demonstrating the
prophylactic role of topical NPWT.100
Another RCT demonstrated a decreased development of
postoperative seromas following incisional NPWT after total hip arthroplasty.101
NPWT has also
been shown to decrease the rate of incisional wound dehiscence following abdominal wall
reconstruction (9% compared with 39% in the original dressing group).102
FEAs further support
the role of NPWT in preventing wound dehiscence. FEA simulations demonstrated a reduction in
peri-incisional lateral stress of approximately 50% following NPWT. Additionally, the directions
of these stress vectors were seen to mimic the distribution found in intact tissue.103
have led to the development of commercial systems such as Prevena, designed speciﬁcally for
incisional wound management. In contrast, Masden and colleagues104
patients with lower extremity and abdominal wound incisions to VAC therapy or a dressing
consisting of a nonadherent layer (Mepitel, Mölnlycke Health Care AB, Göteborg, Sweden) and a
Fig. 17. Intra-abdominal MDWT following lesser sac marsupialization. (Modiﬁed and reprinted with permission by
Wiley from Sermoneta et al.94
) Please note that the lumbostomy drains have been omitted in this illustration. (Color
version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331322
silver dressing (Acticoat, Smith & Nephew, Hull, United Kingdom) and found no statistically
signiﬁcant difference in the rates of infection and dehiscence between the 2 groups.
Skin graft immobilization
The take of STSGs is governed by many factors including the vascularity of the wound surface,
immobilization of the skin graft, and avoidance of infection seroma or hematoma.105
tie-over bolsters immobilize the graft by applying gentle pressure and are left in place for several
days. NPWT has been used by several groups instead of a bolster.106,107
The suction applied to
the interface materials stabilizes the graft and eliminates excess ﬂuids.106,107
the contact zone for graft integration, aiding in the processes of plasmatic imbibition and
Several prospective randomized clinical trials have shown the effectiveness of
using NPWT systems for skin graft immobilization.105-108
For congested lower extremity pedicle ﬂaps and free ﬂaps without anastomotic thrombosis,
NPWT can improve and resolve tissue edema and venous insufﬁciency, prevent further ﬂap
necrosis, and promote granulation, thereby avoiding the risk of further surgical re-
In random local ﬂaps prone to ischemia and distal necrosis for complex ankle
wounds, NPWT contributes to their viability by decreasing venous congestion.110
retrospective study, NPWT was thought to reduce healing complications of large back donor
sites used for free ﬂaps for head and neck reconstruction.111
Degloving injuries involve the shearing of skin and subcutaneous tissue from the underlying
fascia and muscle, including the avulsion of musculocutaneous and fasciocutaneous perfo-
If left alone, the degloved skin will predictably die. After excising the degloved skin and
removing the fat from the dermis, the skin can then be reapplied to the wound as a full-
thickness skin graft. A NPWT device can then be placed on the graft for immobilization.112,113
Combining NPWT with a dermal regeneration template is an additional option and has shown
both excellent functional and esthetic results in treating a subtotal degloving injury of the right
lower limb. In a case study, Dini and colleagues applied NPWT directly to the wound bed for the
ﬁrst 10 days, providing temporary wound closure and early granulation tissue development. A
dermal regeneration template was then applied directly to the wound bed and covered with a
NPWT device. Following an additional 21 days of NPWT with Integra, the cryopreserved
degloved ﬂap was successfully grafted to the wound site with a NPWT device used to immobilize
Part IV—Clinical considerations
A wide array of wound types has been reportedly treated with NPWT. The FDA has approved
NPWT for managing poorly healing wounds. Manufacturer guidelines for the widely used
KCI V.A.C. therapy systems list chronic, acute, traumatic, subacute, and dehisced wounds, partial-
thickness burns, ulcers (such as diabetic, pressure, or venous insufﬁciency), ﬂaps and grafts as
indications for use.115
Because inappropriate use of NPWT devices has the potential for patient harm, the clinician
should carefully weigh the risks, beneﬁts, and alternatives of using NPWT. According to the FDA
and KCI guidelines, NPWT is contraindicated in conditions involving (1) necrotic tissue with
eschar present, (2) untreated osteomyelitis, (3) nonenteric and unexplored ﬁstulas, (4) malig-
nancy in the wound, (5) exposed vasculature, (6) exposed nerves, (7) exposed anastomotic site,
and (8) exposed organs.98
In some cases, clinicians have used NPWT despite the established
contraindications. For example, some studies have successfully implemented VAC therapy in
cases of exposed organs,94
exposed anastomotic sites (Fig 18),116
The use of
polyurethane foam under vacuum forces can have detrimental effects when in direct contact
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 323
with exposed neurovasculature, tendons, and organs. Thus, when applying NPWT in close
proximity to these structures, a nonadherent barrier layer (petroleum gauze, nonadherent
dressings, and oil emulsion dressing) placed over the structure is recommended.11
described intra-abdominal dressings consisting of the VAC foam placed inside
sterile bags (3M Steri-Drape Isolation Bag) with holes cut over their entire surface, allowing ﬂuid
absorption while protecting the surrounding tissue.
Patient risk factors and complications
Given the broad scope and relative ease of NPWT implementation, potential risk factors must
be considered. The FDA has identiﬁed a series of patient risk factors and other characteristics
that warrant consideration before NPWT. These include the following: (1) high risk of bleeding
and hemorrhage; (2) ongoing treatment with anticoagulants or platelet aggregation inhibitors;
(3) friable or infected blood vessels, vascular anastomosis, infected wounds, osteomyelitis,
exposed organs, vessels, nerves, tendon, or ligaments, sharp edges at the wound, spinal cord
injury, and enteric ﬁstulas; (4) patient requires magnetic resonance imaging or hyperbaric
chamber or deﬁbrillation; (5) patient weight and size; (6) proximity of foam to vagus nerve;
(7) circumferential dressing application; and (8) mode of therapy (continuous or intermittent
Although NPWT has been used in a large number of patients, a variety of complications have
been reported in clinical trials. Common complications include bleeding, infection, pain, foam
retention within the wound (Fig 19), and tissue adherence. Bleeding and infection occur only
but they have sometimes been associated with death. These reports have been most
common at home or in long-term-care facilities.98
Much care should be exercised in selecting
appropriate patients to use NPWT at home.
Other rare complications have also been reported. For example, reports indicate that stomal
mucocutaneous dehiscence has been observed in patients with open abdomens, likely caused by
tension generated during NPWT, on the proximal bowel of the stoma.118
The interval between
dressing changes can also adversely factor into patient outcomes. In a case, necrotizing fasciitis
developed during NPWT treatment of a stage IV ischial pressure ulcer. The authors cited the
5 days between VAC system dressing changes as a risk factor, masking rapidly spreading
infections long enough to allow for signiﬁcant complications.119
Blast wounds also present
health care providers with a host of potential complications. Caution must be emphasized in
treating with NPWT, particularly, as its indiscriminate use may correlate with an increased
Fig. 18. Treating intra-abdominal abscesses based on the procedure performed by Weidenhagen and colleagues to treat
a perianastomotic abscess following anterior rectal resection. MDWT foam is ﬁrst lead through a guide tube into the
abscess, which is then drained by vacuum suction. (Reprinted with permission by Springer from Weidenhagen et al.116
(Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331324
incidence of sepsis.120
Treatment of deep cavitary defects resulting from blast injuries may
require placing the tail of the foam deep within the cavity, posing an increased risk of foam
Anticipation of complications, vigilance throughout treatment, and prompt reaction
to adverse events would best allow health care teams to successfully mitigate many of the
potential risks associated with NPWT.
Despite the great interest in these new technologies and the exciting results that many have
achieved, NPWT is not a cure for all wounds. When carefully performed studies show no
difference in outcomes, clinicians will need to use other criteria, such as cost or patient comfort,
to help guide them in their decision as to the best wound therapy to offer a particular patient. As
with any wound therapy, if the wound is not progressing, changing to another modality is very
Considerations for selection of appropriate NPWT protocol
A number of factors should be considered when using NPWT including goal of treatment,
suction protocol, and the type of dressing. Granulation tissue growth, edema removal, and ﬂap
or graft immobilization, each need different NPWT pressure protocols and treatment duration.
For example, a chronic ulcer may beneﬁt from continuous suction for the duration of treatment,
whereas in an acute wound, it may be most appropriate to begin with 48 hours of continuous
suction, followed by cycles of intermittent therapy (eg, 5 minutes on and 2 minutes off).11
intermittent NPWT has demonstrated a more profound tissue response,50
but it may not be
suitable in all cases. Intermittent therapy may not be tolerated because of patient discomfort.
The optimal NPWT suction applied to various wounds is not currently known. In our practice, we
used less pressure on circumferential wounds and when used in conjunction with a free ﬂap.
Clinicians are now presented with a variety of interfaces. Reticulated open-pore foams have
the most evidence behind them and have been shown to create tissue microdeformation.12
These foams also have the capacity to transmit suction over long distances. More data are
required to best inform surgeons of the optimal interface material for a particular clinical
situation. Wounds with an increased risk of infection may require an increased frequency in
Clinical use: device application
Correct placement of the interface material is essential for successful NPWT. We like to cut
the foam so that it is slightly smaller than the wound and insert the interface material into all
undermined areas or tracks. When possible, we use just 1 interface material that is carefully cut
to ﬁll any irregularities in the wound. When more than 1 interface is used, it must to be carefully
documented to assure that there are no retained foreign bodies. When granulation tissue is
desired, the foam should be placed directly on the wound surface.18
A nonadherent contact layer
should be used when granulation tissue is not desired or if the interface is over a luminal
structure such as the bowel or large blood vessels. Having the suction port come out at a
Fig. 19. (A) A 39-year-old man with L-1 partial paralysis and left ischial pressure ulcer, treated with MDWT for 2 months.
(B) Foam retention discovered. (C) Healed following removal of foreign body and ﬂap surgery. (Color version of ﬁgure is
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 325
distance from the wound can help minimize the risk of additional pressure necrosis if weight is
placed on the tube. A bridging technique where the foam continues from the wound to another
location is frequently used for wounds located near the perineum or buttock or undermined
wounds with a small skin opening (Fig 20). We avoid placing the foam directly on top of intact
skin and prefer to place this over a polyurethane drape or hydrocolloid dressing.
The duration of treatment is directed by the goals of the therapy. If the device is used to
facilitate granulation tissue formation, either for healing by secondary intention or in
preparation for skin graft, the therapy can continue until the granulation tissue has reached
the level of the skin. Once at skin level, a skin graft can be placed or another type of wound
treatment can be initiated to complete the healing process. If the goal is wound contraction for
ﬂap surgery, for example, therapy should be stopped once there are no changes in wound
measurements after 1-2 weeks. Similarly, if the device is being used to accelerate healing of a
surgical wound, it should be discontinued once there is no progress. In our practice, we rarely
continue NPWT for more than 3 months.
Adverse effects directly attributable to long-term use of the device include skin irritation
from the adhesive drape and odor from the dressing or canister or both. They can be mitigated
by a brief interruption of therapy for a few days. Skin breakdown can be treated with topical
creams or ointments, depending on the etiology of the dermatitis, and wound odor can be
treated by packing the wound with saline gauze dressings or dilute bleach solution (Dakin) for
48-72 hours. Once adverse effects have abated, NPWT can be resumed.
Not all wounds are amenable to a NPWT device. Some patients do not tolerate the therapy
because of pain or sensitivity to the adhesive drape or the foam. Pain may be relieved by
decreasing the pressure on the device. If the pain appears to be associated with the surrounding
skin, the wound can be framed with a hydrocolloid dressing and the adhesive drape placed over
the hydrocolloid. This may decrease the pull and pressure on the skin. If the pain appears to be
exacerbated by the foam contacting the skin edges, a nonadherent dressing can be applied just
covering the skin edges. The adhesive drape may not stay sealed around wounds near the
rectum or over excessive folds in the skin. A hydrocolloid dressing or stoma adhesive can be
placed on the skin to ﬁll in irregularities affecting the seal. Tissue integrity should be carefully
monitored with each dressing change. If bruising or hematomas are observed, ﬁrst the pressure
is lowered. If they persist, the device should be discontinued. On occasion, the wound bed can
become a dusky gray or light pink color. The pressure can be lowered but the device should be
removed if the wound bed appears ischemic.
Part V—Future perspectives
Foam pore size has been shown to be directly related to the amount of granulation tissue
formation. Larger pores stimulate more granulation tissue formation in a diabetic mouse
Other interface materials such as polyvinyl alcohol sponges with small pores are
Fig. 20. Bridged dressing following dehisced c-section wound. (Color version of ﬁgure is available online.)
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331326
nonadherent, with little tissue ingrowth. Several authors have instilled a variety of solutions into
these devices, which may be effective, particularly when treating wounds with high bioburden
Most biological systems have a more robust response when subjected to variable rather than
continuous mechanical forces. In a preclinical model, we found that applying NPWT for 4 hours
every 2 days gave a similar granulation tissue response as continuous therapy. Surprisingly,
when faster cycle times were used, there was less granulation tissue formed, suggesting that too
fast of a cycle time may damage nascent granulation tissue.35,122,123
Current devices are often limited to obtaining a good seal at the edges of the device, making it
difﬁcult to maintain suction. Advances in adhesive science to allow better adhesion around
curved and moist surfaces would make the device more easily applied to difﬁcult wounds.
The efﬁcacy of NPWT in promoting wound healing has been largely accepted by clinicians,
yet the number of high-level clinical studies demonstrating its effectiveness is small and much
more can be learned about the mechanisms of action. In the future, hopefully we will have the
data to assist clinicians in selecting optimal parameters for speciﬁc wounds including interface
material, waveform of suction application, and the amount of suction to be applied. Further
investigation into speciﬁc interface coatings and instillation therapy are also needed. We believe
that advances in mechanobiology, the science of wound healing, the understanding of bioﬁlms,
and advances in cell therapy will lead to better care for our patients.
1. Schaum KD. A new Medicare part B wound care policy. Adv Skin Wound Care. 2001;14(5):238–240.
2. Orgill DP, Bayer L, Neuwalder J, Felter R. Microdeformational Wound Therapy—A New Era in Wound Healing.
Business Brieﬁng: Global Surgery—Future Directions. 2005:1-3.
3. Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical
experience. Ann Plast Surg. 1997;38(6):563–576. [discussion 577].
4. Meyer W, Schmieden V, Gustav Bier AK. Bier's hyperemic treatment. Surgery, Medicine, and the Specialties: A Manual
of its Practical Application.Philadelphia and London: W.B. Saunders Company; 1908.
5. Neumann CG. The expansion of an area of skin by progressive distention of a subcutaneous balloon; use of the
method for securing skin for subtotal reconstruction of the ear. Plast Reconstr Surg (1946). 1957;19(2):124–130.
6. Morykwas MJ, Argenta LC, Shelton-Brown EI, McGuirt W. Vacuum-assisted closure: a new method for wound
control and treatment: animal studies and basic foundation. Ann Plast Surg. 1997;38(6):553–562.
7. Lancerotto L, Bayer LR, Orgill DP. Mechanisms of action of microdeformational wound therapy. Semin Cell Dev Biol.
8. Kairinos N, Solomons M, Hudson DA. Negative pressure wound therapy I: the paradox of negativ-pressure wound
therapy. Plast Reconstr Surg. 2008;123:589–598.
9. Saxena V, Orgill D, Kohane I. A set of genes previously implicated in the hypoxia response might be an important
modulator in the rat ear tissue response to mechanical stretch. BMC Genomics. 2007;8:430.
10. Frequently asked questions about V.A.C.s Therapy. 〈http://middleeast.kci-medical.com/ME-ENG/vacfaqs〉; 2013
11. Mendez-Eastman S. Guidelines for using negative pressure wound therapy. Adv Skin Wound Care. 2001;14(6):
314–322. [quiz 324-315].
12. Orgill DP, Manders EK, Sumpio BE, et al. The mechanisms of action of vacuum assisted closure: more to learn.
13. Scherer SS, Pietramaggiori G, Mathews JC, Prsa MJ, Huang S, Orgill DP. The mechanism of action of the vacuum-
assisted closure device. Plast Reconstr Surg. 2008;122(3):786–797.
14. Borgquist O, Ingemansson R, Malmsjo M. The inﬂuence of low and high pressure levels during negative-pressure
wound therapy on wound contraction and ﬂuid evacuation. Plast Reconstr Surg. 2011;127(2):551–559.
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 327
15. Kairinos N, Solomons M, Hudson DA. The paradox of negative pressure wound therapy–in vitro studies. J Plast
Reconstr Aesthet Surg. 2010;63(1):174–179.
16. Anesater E, Borgquist O, Hedstrom E, Waga J, Ingemansson R, Malmsjo M. The inﬂuence of different sizes and types
of wound ﬁllers on wound contraction and tissue pressure during negative pressure wound therapy. Int Wound J.
17. Kairinos N, Hudson DA, Solomons M. The inﬂuence of different sizes and types of wound ﬁllers on wound
contraction and tissue pressure during negative pressure wound therapy. Int Wound J. 2011;8(6):656–657.
18. Saxena V, Hwang CW, Huang S, Eichbaum Q, Ingber D, Orgill DP. Vacuum-assisted closure: microdeformations of
wounds and cell proliferation. Plast Reconstr Surg. 2004;114(5):1086–1096. [discussion 1097-1088].
19. Ingber DE, Levin M. What lies at the interface of regenerative medicine and developmental biology? Development.
20. McLeod KJ, Lee RC, Ehrlich HP. Frequency dependence of electric ﬁeld modulation of ﬁbroblast protein synthesis.
21. Yang CC, Chang DS, Webb LX. Vacuum-assisted closure for fasciotomy wounds following compartment syndrome
of the leg. J Surg Orthop Adv. 2006;15(1):19–23.
22. Adamkova M, Tymonova J, Zamecnikova I, Kadlcik M, Klosova H. First experience with the use of vacuum assisted
closure in the treatment of skin defects at the burn center. Acta Chir Plast. 2005;47(1):24–27.
23. Labanaris AP, Polykandriotis E, Horch RE. The effect of vacuum-assisted closure on lymph vessels in chronic
wounds. J Plast Reconstr Aesthet Surg. 2009;62(8):1068–1075.
24. Winter GD, Scales JT. Effect of air drying and dressings on the surface of a wound. Nature. 1963;197:91–92.
25. Winter GD. Formation of the scab and the rate of epithelization of superﬁcial wounds in the skin of the young
domestic pig. Nature. 1962;193:293–294.
26. Hinman CD, Maibach H. Effect of air exposure and occlusion on experimental human skin wounds. Nature.
27. Kim PJ, Attinger CE, Steinberg JS, et al. Negative-pressure wound therapy with instillation: international consensus
guidelines. Plast Reconstr Surg. 2013;132(6):1569–1579.
28. Gerry R, Kwei S, Bayer L, Breuing KH. Silver-impregnated vacuum-assisted closure in the treatment of recalcitrant
venous stasis ulcers. Ann Plast Surg. 2007;59(1):58–62.
29. Orgill DP, Blanco C. Biomaterials for Treating Skin Loss. Boca Raton, FL: CRC Press; 2009.
30. Nuutila K, Siltanen A, Peura M, et al. Gene expression proﬁling of negative-pressure-treated skin graft donor site
wounds. Burns. 2013;39(4):687–693.
31. Ingber DE. The mechanochemical basis of cell and tissue regulation. Mech Chem Biosyst. 2004;1(1):53–68.
32. Alford PW, Nesmith AP, Seywerd JN, Grosberg A, Parker KK. Vascular smooth muscle contractility depends on cell
shape. Integr Biol. 2011;3(11):1063–1070.
33. Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE. Geometric control of cell life and death. Science. 1997;276
34. Ingber DE. Mechanical control of tissue growth: function follows form. Proc Natl Acad Sci U S A. 2005;102(33):
35. Scherer SS, Pietramaggiori G, Mathews JC, Orgill DP. Short periodic applications of the vacuum-assisted closure
device cause an extended tissue response in the diabetic mouse model. Plast Reconstr Surg. 2009;124(5):
36. Huang S, Ingber DE. The structural and mechanical complexity of cell-growth control. Nat Cell Biol. 1999;1(5):
37. Baldwin C, Potter M, Clayton E, Irvine L, Dye J. Topical negative pressure stimulates endothelial migration and
proliferation: a suggested mechanism for improved integration of Integra. Ann Plast Surg. 2009;62(1):92–96.
38. Potter MJ, Banwell P, Baldwin C, et al. In vitro optimisation of topical negative pressure regimens for angiogenesis
into synthetic dermal replacements. Burns. 2008;34(2):164–174.
39. McNulty AK, Schmidt M, Feeley T, Kieswetter K. Effects of negative pressure wound therapy on ﬁbroblast viability,
chemotactic signaling, and proliferation in a provisional wound (ﬁbrin) matrix. Wound Repair Regen. 2007;15(6):
40. Lu F, Ogawa R, Nguyen DT, et al. Microdeformation of three-dimensional cultured ﬁbroblasts induces gene
expression and morphological changes. Ann Plast Surg. 2011;66(3):296–300.
41. Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage speciﬁcation. Cell. 2006;126(4):
42. Erba P, Ogawa R, Ackermann M, et al. Angiogenesis in wounds treated by microdeformational wound therapy.
Ann Surg. 2011;253(2):402–409.
43. Wackenfors A, Sjogren J, Gustafsson R, Algotsson L, Ingemansson R, Malmsjo M. Effects of vacuum-assisted closure
therapy on inguinal wound edge microvascular blood ﬂow. Wound Repair Regen. 2004;12(6):600–606.
44. Greene AK, Puder M, Roy R, et al. Microdeformational wound therapy: effects on angiogenesis and matrix
metalloproteinases in chronic wounds of 3 debilitated patients. Ann Plast Surg. 2006;56(4):418–422.
45. Younan GJ, Heit YI, Dastouri P, et al. Mast cells are required in the proliferation and remodeling phases of
microdeformational wound therapy. Plast Reconstr Surg. 2011;128(6):649e–658e.
46. Ingber DE. Tensegrity-based mechanosensing from macro to micro. Prog Biophys Mol Biol. 2008;97(2-3):163–179.
47. Ingber DE. Mechanobiology and diseases of mechanotransduction. Ann Med. 2003;35(8):564–577.
48. Huang C, Ogawa R. Fibroproliferative disorders and their mechanobiology. Connect Tissue Res. 2012;53(3):187–196.
49. Wilkes RP, McNulty AK, Feeley TD, Schmidt MA, Kieswetter K. Bioreactor for application of subatmospheric
pressure to three-dimensional cell culture. Tissue Eng. 2007;13(12):3003–3010.
50. Younan G, Ogawa R, Ramirez M, Helm D, Dastouri P, Orgill DP. Analysis of nerve and neuropeptide patterns in
vacuum-assisted closure-treated diabetic murine wounds. Plast Reconstr Surg. 2010;126(1):87–96.
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331328
51. Torbrand C, Wackenfors A, Lindstedt S, Ekman R, Ingemansson R, Malmsjo M. Sympathetic and sensory nerve
activation during negative pressure therapy of sternotomy wounds. Interact Cardiovasc Thorac Surg. 2008;7(6):
52. Barker AR, Rosson GD, Dellon AL. Wound healing in denervated tissue. Ann Plast Surg. 2006;57(3):339–342.
53. Morykwas MJ, Simpson J, Punger K, Argenta A, Kremers L, Argenta J. Vacuum-assisted closure: state of basic
research and physiologic foundation. Plast Reconstr Surg. 2006;117(suppl 7):121S–126S.
54. Assadian O, Assadian A, Stadler M, Diab-Elschahawi M, Kramer A. Bacterial growth kinetic without the inﬂuence of
the immune system using vacuum-assisted closure dressing with and without negative pressure in an in vitro
wound model. Int Wound J. 2010;7(4):283–289.
55. Moues CM, Vos MC, van den Bemd GJ, Stijnen T, Hovius SE. Bacterial load in relation to vacuum-assisted closure
wound therapy: a prospective randomized trial. Wound Repair Regen. 2004;12(1):11–17.
56. Yusuf E, Jordan X, Clauss M, Borens O, Mader M, Trampuz A. High bacterial load in negative pressure wound
therapy (NPWT) foams used in the treatment of chronic wounds. Wound Repair Regen. 2013;21(5):677–681.
57. Joseph E, Hamori CA, Bergman S, Roaf E, Swann NF, Anastasi GW. A prospective, randomized trial of vacuum-
assisted closure versus standard therapy of chronic nonhealing wounds. Wounds. 2000;12:60–67.
58. Schwien T, Gilbert J, Lang C. Pressure ulcer prevalence and the role of negative pressure wound therapy in home
health quality outcomes. Ostomy Wound Manage. 2005;51(9):47–60.
59. Nakayama M. Applying negative pressure therapy to deep pressure ulcers covered by soft necrotic tissue.
Int Wound J. 2010;7(3):160–166.
60. Yao M, Fabbi M, Hayashi H, et al. A retrospective cohort study evaluating efﬁcacy in high-risk patients with chronic
lower extremity ulcers treated with negative pressure wound therapy. Int Wound J. 2012, doi: 10.1111/j.1742-481X.
61. Nather A, Hong NY, Lin WK, Sakharam JA. Effectiveness of bridge V.A.C. dressings in the treatment of diabetic foot
ulcers. Diabet Foot Ankle. 2011;2:5893.
62. Ulusal AE, Sahin MS, Ulusal B, Cakmak G, Tuncay C. Negative pressure wound therapy in patients with diabetic foot.
Acta Orthop Traumatol Turc. 2011;45(4):254–260.
63. Patel RM, Nagle DJ. Nonoperative management of scleroderma of the hand with tadalaﬁl and subatmospheric
pressure wound therapy: case report. J Hand Surg. 2012;37(4):803–806.
64. Zutt M, Haas E, Kruger U, Distler M, Neumann C. Successful use of vacuum-assisted closure therapy for leg ulcers
caused by occluding vasculopathy and inﬂammatory vascular diseases—a case series. Dermatology. 2007;214(4):
65. Oh BH, Lee SH, Nam KA, Lee HB, Chung KY. Comparison of negative pressure wound therapy and secondary
intention healing after excision of acral lentiginous melanoma on the foot. Br J Dermatol. 2013;168(2):333–338.
66. Katz MS, Finck CM, Schwartz MZ, et al. Vacuum-assisted closure in the treatment of extensive lymphangiomas in
children. J Pediatr Surg. 2012;47(2):367–370.
67. Heit YI, Lancerotto L, Cortes R, et al. Early kinetics of integration of collagen-glycosaminoglycan regenerative
scaffolds in a diabetic mouse model. Plast Reconstr Surg. 2013;132(5):767e–776e.
68. Kang GC, Por YC, Tan BK. In vivo tissue engineering over wounds with exposed bone and tendon: autologous
dermal grafting and vacuum-assisted closure. Ann Plast Surg. 2010;65(1):70–73.
69. Bloemen MC, van der Wal MB, Verhaegen PD, et al. Clinical effectiveness of dermal substitution in burns by topical
negative pressure: a multicenter randomized controlled trial. Wound Repair Regen. 2012;20(6):797–805.
70. Khundkar R, Malic C, Burge T. Use of Acticoat dressings in burns: what is the evidence? Burns. 2010;36(6):751–758.
71. Stinner DJ, Waterman SM, Masini BD, Wenke JC. Silver dressings augment the ability of negative pressure wound
therapy to reduce bacteria in a contaminated open fracture model. J Trauma. 2011;71(suppl 1):S147–S150.
72. Raad W, Lantis 2nd JC, Tyrie L, Gendics C, Todd G. Vacuum-assisted closure instill as a method of sterilizing massive
venous stasis wounds prior to split thickness skin graft placement. Int Wound J. 2010;7(2):81–85.
73. Scimeca CL, Bharara M, Fisher TK, Kimbriel H, Mills JL, Armstrong DG. Novel use of insulin in continuous-instillation
negative pressure wound therapy as “wound chemotherapy”. J Diabetes Sci Technol. 2010;4(4):820–824.
74. Scala M, Spagnolo F, Trapasso M, Strada P, Moresco L, Santi P. Association of vacuum-assisted closure and platelet
gel for the deﬁnitive surgical repair of an enterocutaneous ﬁstula: a case report. In Vivo. 2012;26(1):147–150.
75. Wijewardena A, Vandervord E, Lajevardi SS, Vandervord J, Jackson CJ. Combination of activated protein C and
topical negative pressure rapidly regenerates granulation tissue over exposed bone to heal recalcitrant orthopedic
wounds. Int J Low Extrem Wounds. 2011;10(3):146–151.
76. Masumoto K, Nagata K, Oka Y, et al. Successful treatment of an infected wound in infants by a combination of
negative pressure wound therapy and arginine supplementation. Nutrition. 2011;27(11-12):1141–1145.
77. Rudzka-Nowak A, Luczywek P, Gajos MJ, Piechota M. Application of manuka honey and GENADYNE A4 negative
pressure wound therapy system in a 55-year-old woman with extensive phlegmonous and necrotic lesions in the
abdominal integuments and lumbar region after traumatic rupture of the colon. Med Sci Monit. 2010;16(11):
78. Ganacias-Acuna EF. Active Leptospermum honey and negative pressure wound therapy for nonhealing postsurgical
wounds. Ostomy Wound Manage. 2010;56(3):10–12.
79. Li J, Topaz M, Tan H, et al. Treatment of infected soft tissue blast injury in swine by regulated negative pressure
wound therapy. Ann Surg. 2013;257(2):335–344.
80. International Concensus. Appropriate use of silver dressings in wounds. An expert working group concensus.
81. Blum ML, Esser M, Richardson M, Paul E, Rosenfeldt FL. Negative pressure wound therapy reduces deep infection
rate in open tibial fractures. J Orthop Trauma. 2012;26(9):499–505.
82. Lee SY, Niikura T, Miwa M, et al. Negative pressure wound therapy for the treatment of infected wounds with
exposed knee joint after patellar fracture. Orthopedics. 2011;34(6):211.
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331 329
83. Barnett TM, Shilt JS. Use of vacuum-assisted closure and a dermal regeneration template as an alternative to ﬂap
reconstruction in pediatric grade IIIB open lower-extremity injuries. Am J Orthop. 2009;38(6):301–305.
84. Hou Z, Irgit K, Strohecker KA, et al. Delayed ﬂap reconstruction with vacuum-assisted closure management of the
open IIIB tibial fracture. J Trauma. 2011;71(6):1705–1708.
85. Steingrimsson S, Gottfredsson M, Gudmundsdottir I, Sjogren J, Gudbjartsson T. Negative-pressure wound therapy
for deep sternal wound infections reduces the rate of surgical interventions for early re-infections. Interact
Cardiovasc Thorac Surg. 2012;15(3):406–410.
86. Damiani G, Pinnarelli L, Sommella L, et al. Vacuum-assisted closure therapy for patients with infected sternal
wounds: a meta-analysis of current evidence. J Plast Reconstr Aesthet Surg. 2011;64(9):1119–1123.
87. De Feo M, Vicchio M, Nappi G, Cotrufo M. Role of vacuum in methicillin-resistant deep sternal wound infection.
Asian Cardiovasc Thorac Ann. 2010;18(4):360–363.
88. Doss M, Martens S, Wood JP, Wolff JD, Baier C, Moritz A. Vacuum-assisted suction drainage versus conventional
treatment in the management of poststernotomy osteomyelitis. Eur J Cardiothorac Surg. 2002;22(6):934–938.
89. Tocco MP, Ballardini M, Masala M, Perozzi A. Post-sternotomy chronic osteomyelitis: is sternal resection always
necessary? Eur J Cardiothorac Surg. 2013;43(4):715–721.
90. Tocco MP, Costantino A, Ballardini M, et al. Improved results of the vacuum assisted closure and Nitinol clips
sternal closure after postoperative deep sternal wound infection. Eur J Cardiothorac Surg. 2009;35(5):833–838.
91. Gallo O, Deganello A, Meccariello G, Spina R, Peris A. Vacuum-assisted closure for managing neck abscesses
involving the mediastinum. Laryngoscope. 2012;122(4):785–788.
92. Sziklavari Z, Grosser C, Neu R, et al. Complex pleural empyema can be safely treated with vacuum-assisted closure.
J Cardiothorac Surg. 2011;6:130.
93. Rispoli DM, Horne BR, Kryzak TJ, Richardson MW. Description of a technique for vacuum-assisted deep drains in
the management of cavitary defects and deep infections in devastating military and civilian trauma. J Trauma.
94. Sermoneta D, Di Mugno M, Spada PL, et al. Intra-abdominal vacuum-assisted closure (VAC) after necrosectomy for
acute necrotising pancreatitis: preliminary experience. Int Wound J. 2010;7(6):525–530.
95. Bemelman WA. Vacuum assisted closure in coloproctology. Tech Coloproctol. 2009;13(4):261–263.
96. Choi WW, McBride CA, Kimble RM. Negative pressure wound therapy in the management of neonates with
complex gastroschisis. Pediatr Surg Int. 2011;27(8):907–911.
97. Kilbride KE, Cooney DR, Custer MD. Vacuum-assisted closure: a new method for treating patients with giant
omphalocele. J Pediatr Surg. 2006;41(1):212–215.
98. FDA Safety Communication: UPDATE on Serious Complications Associated with Negative Pressure Wound
Therapy Systems [webpage]. 〈http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm244211.htm〉; 2011
99. Kilpadi DV, Cunningham MR. Evaluation of closed incision management with negative pressure wound therapy
(CIM): hematoma/seroma and involvement of the lymphatic system. Wound Repair Regen. 2011;19(5):588–596.
100. Stannard JP, Volgas DA, McGwin 3rd G, et al. Incisional negative pressure wound therapy after high-risk lower
extremity fractures. J Orthop Trauma. 2012;26(1):37–42.
101. Pachowsky M, Gusinde J, Klein A, et al. Negative pressure wound therapy to prevent seromas and treat surgical
incisions after total hip arthroplasty. Int Orthop. 2012;36(4):719–722.
102. Conde-Green A, Chung TL, Holton 3rd LH, et al. Incisional negative-pressure wound therapy versus conventional
dressings following abdominal wall reconstruction: a comparative study. Ann Plast Surg. 2013;71(4):394–397.
103. Wilkes RP, Kilpad DV, Zhao Y, Kazala R, McNulty A. Closed incision management with negative pressure wound
therapy (CIM): biomechanics. Surg Innov. 2012;19(1):67–75.
104. Masden D, Goldstein J, Endara M, Xu K, Steinberg J, Attinger C. Negative pressure wound therapy for at-risk surgical
closures in patients with multiple comorbidities: a prospective randomized controlled study. Ann Surg. 2012;255
105. Llanos S, Danilla S, Barraza C, et al. Effectiveness of negative pressure closure in the integration of split thickness
skin grafts: a randomized, double-masked, controlled trial. Ann Surg. 2006;244(5):700–705.
106. Petkar KS, Dhanraj P, Kingsly PM, et al. A prospective randomized controlled trial comparing negative pressure
dressing and conventional dressing methods on split-thickness skin grafts in burned patients. Burns. 2011;37(6):
107. Azzopardi EA, Boyce DE, Dickson WA, et al. Application of topical negative pressure (vacuum-assisted closure) to
split-thickness skin grafts: a structured evidence-based review. Ann Plast Surg. 2013;70(1):23–29.
108. Moisidis E, Heath T, Boorer C, Ho K, Deva AK. A prospective, blinded, randomized, controlled clinical trial of topical
negative pressure use in skin grafting. Plast Reconstr Surg. 2004;114(4):917–922.
109. Vaienti L, Gazzola R, Benanti E, et al. Failure by congestion of pedicled and free ﬂaps for reconstruction of lower
limbs after trauma: the role of negative-pressure wound therapy. J Orthop Traumatol. 2013;14(3):213–217.
110. Goldstein JA, Iorio ML, Brown B, Attinger CE. The use of negative pressure wound therapy for random local ﬂaps at
the ankle region. J Foot Ankle Surg. 2010;49(6):513–516.
111. Schmedes GW, Banks CA, Malin BT, Srinivas PB, Skoner JM. Massive ﬂap donor sites and the role of negative
pressure wound therapy. Otolaryngol Head Neck Surg. 2012;147(6):1049–1053.
112. Meara JG, Guo L, Smith JD, Pribaz JJ, Breuing KH, Orgill DP. Vacuum-assisted closure in the treatment of degloving
injuries. Ann Plast Surg. 1999;42(6):589–594.
113. Morris M, Schreiber MA, Ham B. Novel management of closed degloving injuries. J Trauma. 2009;67(4):E121–E123.
114. Dini M, Quercioli F, Mori A, Romano GF, Lee AQ, Agostini T. Vacuum-assisted closure, dermal regeneration template
and degloved cryopreserved skin as useful tools in subtotal degloving of the lower limb. Injury. 2012;43(6):
Therapy Forms and Brochures. 〈http://www.kci1.com/KCI1/vactherapyformsandbrochures〉 [accessed
C. Huang et al. / Current Problems in Surgery 51 (2014) 301–331330