ArticlePDF AvailableLiterature Review

Maceration of the skin and wound bed. 1: Its nature and causes.

Authors:
  • Hertfordshire
  • DDRC Wound Care

Abstract

Maceration, caused by prolonged exposure to moisture, can complicate the healing of wounds, especially chronic ones. This paper--the first of three reviewing the literature on its aetiology and management--looks at how maceration occurs.
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JOURNAL OF WOUND CARE VOL 11, NO 7, JULY 2002 275
References
1 Anderson, K.N. (Ed.)
Mosby’s Medical Nursing
and Allied Health
Dictionary. St. Louis,
Mosby-Year Book Inc, 1998.
2 Charcot, J.M. On
Diseases of the Nervous
System.Translated by
Sigerson, G. New Sydenham
Society 1877; 63: 126.
3 Falanga,V.Wound bed
preparation for optimal use
of advanced therapeutic
products. www.bu.edu/
woundbiotech/woundcare/
Woundbedpr.html; 2000,
accessed 24 April 2002.
4 Cocke,W.M.,White, R.R.,
Lynch, D.J. ,Verheyden, C.N.
Wound Care. New York:
Churchill Livingstone, 1984.
5 Harding, K.G., Hughes,
L.E., Marks, J.A guide to the
practical management of
granulating wounds. Cardiff:
Department of Surgery,
University of Wales, College
of Medicine/Dow Corning
Valbonne Cedex, 1986.
6 Jordan, M.M., Clark, M.
Report on Incidence of
Pressure Sore in the
Patient Community of the
Greater Glasgow Health
Board Area. Glasgow:
University of Strathclyde,
21 January 1977.
Maceration of the skin and wound
bed 1: its nature and causes
Maceration, caused by prolonged exposure to moisture, can complicate the healing
of wounds, especially chronic ones. This paper — the first of three reviewing the
literature on its aetiology and management — looks at how maceration occurs
healthy wounds; chronic wounds; exudate; transudate; transepidermal water loss; oedema
Keith F. Cutting, MN,
RGN, RMN, Dip N
(Lond), Cert Ed,
Principal Lecturer,
Buckinghamshire
Chilterns University
College, Newland Park,
Chalfont St Giles, UK
Email
kcuttin01@bsuc.ac.uk
Richard J White, PhD,
Clinical research
consultant, Medical
Communications,
Highbury,Whitstone, UK.
Email
info@medicalwriter.co.uk
M
aceration (from the Latin maceratio
to make wet/soften) is defined as the
softening and breaking down of skin
resulting from prolonged exposure to
moisture.
1
Originally described by
Charcot in 1877
2
it occurs typically in and around
the wound bed in acute and chronic wounds. Macer-
ation can complicate the healing of chronic wounds.
Healthy, non-macerated wound
Perversely, comprehensive descriptions of healthy
wounds are difficult to come by, as many focus on
features that identify an unhealthy state. Currently,
clinicians are concentrating on priming the
wounded tissue to provide optimal conditions
for healing — ‘wound bed preparation’,
3
although
the characteristics that hinder healing, necessitat-
ing removal from the wound i.e. infection,
necrotic/fibrous tissue and exudate, are addressed.
A definitive description of how a healthy wound
should appear once these impediments to healing
have been addressed is not included.
3
One is
tempted to ask: if you don’t know where you are
going how do you know you have got there?
Cocke et al
4
state that healthy granulation tissue
has a fine, granular surface and is red with a velvety
texture, a definition that many still accept as accu-
rate. Harding et al
5
offer a more comprehensive
description of a healthy wound: ‘A healthy wound
is neither inflamed nor inert in appearance, not
painful or tender to touch, has no excessive dis-
charge and does not bleed on light pressure; it heals
without interruption at a fairly predictable rate.
However, the process of repair in an open wound is
complex and individuals differ in the way their tis-
sues react to injury. The extent of normal variation
in wound appearance should be learnt to avoid
unnecessary anxiety or intervention.’
Causes of maceration
Maceration is caused by excessive amounts of aque-
ous fluid in contact with the skin or wound surface
for extended periods. This fluid may be produced by
the wound itself (exudate), or may be a result of uri-
nary incontinence
2
, excessive sweating, or water
lost through the skin by the process of transepider-
mal water loss (TEWL).
Excessive exposure to moisture causes deteriora-
tion of a wound and may lead to skin break-down.
A strong relationship exists between excessive skin
moisture, regardless of source and the development
of pressure ulcers.
6,7
Cochrane
8
states that ‘skin
should be kept clean and dry to prevent maceration.
Damp skin breaks down more easily under axial
pressure and shear forces.’
Composition of wound exudate
Transudates and exudates are serum derivatives.
9
A
transudate (an ultrafiltrate of blood) has a low pro-
tein content, with a specific gravity of less than
1.020. The presence of a transudate implies a non-
inflammatory source of the fluid, such as increased
hydrostatic pressure that exceeds oncotic pressure.
Exudates have a high protein content and a spe-
cific gravity greater than 1.020. They contain
inflammatory components, such as leukocytes, fib-
rinogen, fibrin, and will thus promote clotting.
10
Exudate varies in appearance and composition
according to the aetiology and condition of the
wound. It is normally a pale straw colour and
watery in appearance but may become discoloured
and viscous in the presence of infection. Different
types of exudate may be seen in Box 1.
11-13
Exudate (serous) is not per se a bad thing, as it pro-
vides essential nutrients for epithelial cells, facili-
tates the ingress of white cells and provides the
moist environment so important for healing. The
normal response to healing, inflammation, leads to
the development of local oedema. Histamine
released from damaged cells as a result of wounding
causes plasma leakage from blood vessels. As a con-
sequence oedema forms in the adjacent tissues.
This fluid, exudate, that seeps from the wound
surface is initially a clear, serous liquid. Later this
liquid may become more viscous and opaque due to
leukocytes and other constituents such as albumin,
macrophages and cellular debris. Although there is
limited understanding of exudate, Thomas
14
lists
7 Thyagarajan, C., Silver, J.R.
Aetiology of pressure sores
in patients with spinal cord
injury. BMJ 1984; 289:
1487-1490.
8 Cochrane, G. The
Severely Disabled. In: Bader,
D.L. (Ed.) Pressure Sores
— Clinical Practice and
Scientific Approach.
London: Macmillan, 1990.
9 Price, S.A.,Wilson, L.M.
Pathophysiology. 4th
Edition. St Louis, Mo:
Mosby, 1992.
10 Vickery, C. 1997.
Exudate — what is it and
what is its function in acute
and chronic wounds? In:
(Eds) Cherry, G., Harding,
K. Management of Wound
Exudate. Proceedings Joint
Meeting European Wound
Management Association
and European Tissue Repair
Society. London: Churchill
Communications, 1997.
11 Chen, J. Aquacel
hydrofibre dressing: the
next step in wound
dressing technology.
Monograph. London:
ConvaTec, 1998.
12 Harding, K. Is exudate a
clinical problem? In: (Eds)
Cherry, G., Harding, K.
Management of Wound
Exudate. Proceedings Joint
Meeting European Wound
Management Association
and European Tissue Repair
Society. London: Churchill
Communications, 1997.
13 Cooper, R.M. Personal
communication to the
authors: 25 April, 2002.
14 Thomas, S. 1997.
Exudate — Who Needs It?
Proceedings Joint Meeting,
European Wound
Management Association
and European Tissue
Repair Society.
Management of Wound
Exudate. London: Churchill
Communications, 1997.
15 Dale, J. 1995.The
anatomy and physiology of
the circulation of the leg.
In: (Eds.) Callum, M., Roe, B.
Leg Ulcers Nursing
Management. London:
Scutair Press, 1995.
16 Dale J. 1995.The
aetiology of leg ulceration.
In: (Eds.) Callum, M., Roe, B.
Leg Ulcers Nursing
Management. London:
Scutair Press, 1995.
17 Lamke, L. Nilsson, G.E.,
Reithner, H.L.The
evaporative water loss
from burns and water
permeability of grafts and
artificial membranes used
in the treatment of burns.
Burns 1997; 3: 159-165.
some of the factors that may influence its produc-
tion (Box 2), citing observations by others.
15-19
Acute wound exudate
Acute wound exudate has been shown to differ
from that produced by chronic wounds. Although
acute wound exudate contains metalloproteinases,
they are inactive (pro-enzyme stage) and chronic
wound fluid contains a greater variety of these
enzymes in higher concentrations.
20
Additionally,
in acute wounds α1-antitrypsin-degrading enzymes
are absent but present in chronic wounds. Likewise
polymorphonuclearcyte (PMN) elastase levels are
normal and fibronectin remains intact in acute
wounds but in chronic wounds PMN elastase levels
are high and fibronectin is degraded.
21
Chronic wound exudate
Qualitative differences have been identified
between exudates from acute and chronic
wounds.
22-26
Chronic wound exudate is predomi-
nantly blood serum with most platelets and ery-
throcytes removed: it is, however, enriched with
white blood cells.
14
These serve as a source of pro-
teases, particularly matrix metalloproteinases
(MMPs); enzymes which by definition break down
protein and may actively damage what may be oth-
erwise healthy tissue.
24
This has led to chronic
wound fluid being regarded as a ‘wounding agent’
in its own right.
11
MMPs and plasminogen activators are endoge-
nous extracellular matrix-degrading enzymes found
in exudate. Their purpose is to remove fibrin and
eschar from the wound.
20,23,27
In the normal,
healthy healing situation MMPs are regulated by
naturally occurring endogenous inhibitors known
as tissue inhibitors of metalloproteinases —
TIMPs.
28
This aspect of chronic wound pathophysi-
ology has led to a greater understanding of how
exudate can lead directly to wound enlargement, by
enzymatic degradation of exposed ‘healthy’ skin, if
not controlled adequately. Furthermore, it has
resulted in therapies that may be used to treat
chronic wounds.
29
Clinical implications
When a wound deteriorates, as is the case when
infected, it may exhibit an increase in level of exu-
date production (appearance/content continuum).
Clothes or bedclothes may become soiled, there
may be a change in odour and dressings may
require more frequent change, or may leak.
If a wound with moderate or higher levels of exu-
date is inappropriately dressed, then exudate-medi-
ated maceration is a likely outcome. Chronic
wounds such as leg ulcers, pressure ulcers and dia-
betic foot ulcers will exhibit this if the dressing can-
not cope with exudate output or if the dressing
wear time is too long. This maceration is generally
evident as an opaque or white ‘soggy’ area of peri-
ulcer skin that occurs when the wound is moder-
ately to heavily exuding. It is most evident where
there is thick calloused skin, as is typical around
plantar ulcers. Maceration of the wound bed does
occur occasionally, but after searching the litera-
ture, a definitive description to assist clinical identi-
fication could not be found. It would be reasonable
to presume that maceration of the wound bed is less
obvious to the eye than peri-wound skin or callus
maceration.
Increased levels of wound exudate are conducive
to bacterial wound colonisation.
30
The risk is proba-
bly increased in wounds that are not appropriately
managed. However, despite the possibility of non-
occlusive dressings becoming soaked with exudate
and thereby providing access for bacteria, there is
little evidence to support the theory that infection
risk is increased. When macerated tissue is present
and becomes infected it is most likely to be caused
by organisms that prefer an environment with high
water activity, e.g. Staph Aureus, and thereby thrive
in tissues with a high water content.
31
Water, skin and the permeability barrier
It has already been stated that maceration is not
always due to exudate; other aqueous liquids such
as water and urine also have this effect. The effect of
water is particularly evident in hand burns treated
with occlusive gloves.
32
The water is derived from
normal transepidermal water, lost by insensible
transpiration through the normal epidermis
(transepidermal water loss or TEWL). To understand
this concept better, it is necessary to look at the
water permeability barrier in the skin and its func-
276 JOURNAL OF WOUND CARE VOL 11, NO 7, JULY 2002
Box 1. Different types of exudate and
their contents
Serous: Clear, watery consistency. May be a sign of
infection as some bacteria produce fibrinolysins,
enzymes which degrade fibrin clots or coagulated
plasma. Some strains of S. aureus, b-haemolytic group
A streptococci, B. fragilis produce fibrinolysins and P.
aeruginosa produces a non-specific enzyme that
degrades fibrin
13
Fibrinous: Cloudy, contains fibrin protein strands.
Purulent: Pyogenic organisms and other
inflammatory cells.
Haemo-purulent: Contains neutrophils, dead/dying
bacteria and inflammatory cells i.e. established
infection is present. Consequent damage to dermal
capillaries leads to blood leakage.
Haemorrhagic: Capillaries have become so friable
that they easily break down and spontaneous, copious
bleeding occurs. Blood is the major component of this
type of exudate. Not to be confused with bloody
exudate as a result of over enthusiastic debridement.
education
education
tion. It is now accepted that the main functional
component of the barrier is the stratum compactum,
the lowermost layer of the stratum corneum.
33
The barrier serves to restrict the loss of water
through intact skin to a level commensurate with
functional needs and to reduce the ingress of
unwanted materials from the environment. The
region above (exterior) to the compactum is the
stratum disjunctum. It comprises porous, dead cells
in the process of desquamation. These cells contain
hygroscopic materials such as pyrrolidone car-
boxyic acid, sodium chloride, etc, that readily
absorb water. This maintains the plasticity/pliabil-
ity of a normal healthy stratum corneum.
The thickened disjunctum of palmar and plantar
surfaces will absorb water and thicken further, cre-
ating the characteristic wrinkling seen when a per-
son spends too long in the bath. This is the visible
evidence of early maceration. When normal,
healthy skin is occluded, as might be the case with
kitchen film, the TEWL fluid passes through the
epidermal barrier and causes swelling of the dis-
junctum (Fig 1). Removal of the occluding agent
rapidly reverses the excess hydration as evaporation
to the air occurs.
This is not evidence against occlusion; most mod-
ern dressings are not totally occlusive. Some, for
example the hydrocolloids, have sufficient capacity
to absorb and retain transepidermal water loss over
a wear time of seven days. It is the normal evapora-
tion of relatively small quantities of water through
intact skin, and not to be confused with sweating,
transudate or exudate.
Other dressings such as hydropolymer foams
have a high moisture vapour transmission rate
(MVTR); this is a novel physical mechanism for
dressing fluid handling. It involves the absorption
and evaporation of exudate by the dressing, rather
than absorption alone. Fluid is absorbed into the
hydropolymer and from there into a wicking layer.
From here it is able to pass into the air via the back-
ing polyurethane layer.
34
Maceration around the wound
When the skin around a wound is exposed to exu-
date the disjunctum initially absorbs fluid and
swells. Further fluid leads to saturation of the com-
pactum and reduced barrier function. Without bar-
rier protection, the living cells of the epidermis are
next to suffer from over-hydration, hence skin
breakdown follows untreated maceration.
Maceration is most likely to occur in chronic
wounds such as leg ulcers, pressure ulcers, diabetic
foot ulcers, fungating wounds and burns, particu-
Box 2. Factors that may influence exudate production
14
Biochemical changes, Histamine and vasoactive amines give rise to increased vascular permeability
eg with an effect on and extravasation in the inflammatory stage
capillary permeability
Gender An unsubstantiated observation that males produce more exudate than women
14
Hydrostatic pressure Posture,
15
Venous hypertension
16
Temperature Associated with capillary dilation
Type of dressing and Hygroscopic (Mesalt), debriding agents dressing providing
topical treatment back pressure, iodinated dressings
Wound depth and Generally, the deeper the wound the greater the production of exudate. However, in
surface area burns the exudate production remains more or less constant in relation to surface area
17
Wound infection Some bacteria induce vascular permeability. It is recognised that a sudden increase in
exudate may be a response to infection
18
Wound type Exudate production may vary with the type of wound and stage of healing
17,19
JOURNAL OF WOUND CARE VOL 11, NO 7, JULY 2002 277
18 Gilchrist, B.Wound
Infection. In: (Eds.) Miller,
M., Glover, D.Wound
Management Theory and
Practice London: Emap
Healthcare, 1999.
19 Thomas, S., Fear, M.,
Humphreys, J. et al.The
effect of dressings on the
production of exudate
from venous leg ulcers.
Wounds 1996; 8: 5, 145-150.
20 Wysocki,A.B.Wound
fluids and the pathogenesis
of chronic wounds.
JWOCN 1996; 23: 283-290.
21 Rao, C.N., Ladin, D.A.,
Liu,Y.Y. et al.Alpha1-
Antitrypsin is degraded and
non-functional in chronic
wounds but intact and
functional in acute wounds:
the inhibitor protects
fibronectin from
degradation by chronic
wound fluid enzymes. J
Investig Dermatol 1995;
105: 4, 572-578.
22 Chen,W.Y., Rogers,
A.A., Lydon, M.J.
Characterisation of biologic
properties of wound fluid
collected during early
stages of wound healing. J
Invest Dermatol 1992; 99:
5, 559-564.
23 Rogers,A. Burnett, S.,
Moore, J.C. et al.
Involvement of proteolytic
enzymes — plasminogen
activators — in the
pathophysiology of
pressure ulcers.Wound
Repair Regen 1995; 3: 3,
273-283.
24 Trengove, N., Langton,
S.R., Stacey, M.C.
Biochemical analysis of
wound fluid from non-
healing and healing chronic
leg ulcers.Wound Rep
Regen 1996; 4: 234-239.
25 Trengove, N.J., Stacey,
M.C., McAuley, S. et al.
Analysis of acute and
chronic wound
environments: the role of
proteases and their
inhibitors.Wound Repair
Regen 1999; 7: 6, 442-452.
26 Buchan, I.,Andrews, J.K.,
Lang, S.M. et al. Clinical and
laboratory investigations of
the composition and
properties of human skin
wound exudate under
semi-permeable dressings.
Burns 1980; 7: 326-334.
27 Ravanti, L., Matti-Kahari,
V. Matrix metalloproteinases
in wound repair (Review).
Int J Mol Med 2000;
6: 391-407.
Fig 1. A cross-section of the skin
stratum disjunctum
stratum compactum
{
stratum corneum
education
28 Brew, K.,
Dinakarpandian, D., Nagase,
H.Tissue inhibitors of
metalloproteinases:
evolution, structure and
function. Biochim et
Biophys Acta 2000; 1477:
267-283.
29 Cullen, B, Smith, R.,
McCulloch, E. et al.The
mechanism of action of
Promogran, a proteinase
modulating matrix.Wound
Repair Regen 2002; 10: 1,
16-25.
30 Armstrong, S.H.,
Ruckley, C.V. Use of a
fibrous dressing in exuding
leg ulcers. J Wound Care
1997; 6: 7, 322-324.
31 Troller, J.A., Stinson, J.V.
Influence of water activity
on the production of
extracellular enzymes by
Staphylococcus aureus.
Appl Environ Microbiol
1978; 35: 3; 521-526.
32 Terrill, P.J., Kedwards,
S.M ., Lawrence, J.C. The
use of Gore-Tex bags for
hand burns. Burns 1991; 17:
2; 161-165.
33 Bowser, P.A.,White, R J.
Isolation, barrier properties
and lipid analysis of stratum
compactum, a discrete
region of the stratum
corneum. Brit J Dermatol
1985; 112: 1-14.
34 Schultze, H.-J., Lane, C.,
Charles, H. et al. Evaluating
a superabsorbent
hydropolymer dressing for
exuding venous leg ulcers. J
Wound Care 2001; 10: 1,
511-520.
35 Nelson,A. Is Exudate a
Clinical Problem. In: (Eds.)
Cherry, G., Harding, K.
Proceedings, Joint Meeting,
European Wound
Management Association
and European Tissue Repair
Society. Management of
Wound Exudate. London:
Churchill Communications
Europe, 1997.
36 Bolton, L.L., Monte, K.,
Pirone L.A. Moisture and
healing: beyond the jargon.
Ost Wound Man 2000; 46:
1A (Suppl), 51S-62S.
37 Scheuplein, R.J.
Mechanisms of percutaneous
absorption. 1 Routes of
penetration and the influence
of solubility. J Invest Dermatol
1965; 45: 334-346.
38 Blank, I.H.The effect of
hydration on the
permeability of the skin. In:
(Eds.) Bronaugh, R.L.,
Maibach, H.I. Percutaneous
Absorption — Mechanisms
— Methodology — Drug
Delivery. New York: Marcel
Dekker Inc, 1985.
larly where occlusive therapy is used inappropri-
ately. For example, patients who are bed-ridden and
are incontinent of urine are at risk of developing
lesions on the buttocks or sacrum; in obese individ-
uals lesions may occur between folds of skin, for
example sub mammary intertrigo. Nelson
35
has
indicated that when maceration occurs this may
lead to an increase in the overall size of the lesion
with excoriation and pain. Additional conse-
quences for the patient are: longer treatment time,
added discomfort, modified treatment regime and
uncertainty about wound progress. For the health
service provider increased costs result from longer
treatment time and additional material resources, as
well as possible increased staff costs.
In the healing wound, the advancing rim of new
epithelium often appears pale and slightly opaque.
The inexperienced practitioner may interpret this
as the effects of maceration
36
(Fig 2).
This delicate tissue, produced in a moist environ-
ment, may subsequently be exposed to inappropri-
ate measures in a futile attempt to reverse the
perceived maceration. The deleterious effects of des-
iccation generated by application of a dry dressing
will impede the healing process. If the observer
waits for a day or two the supposed ‘unhealthy’
white epithelium will be seen to change to a
healthy pink. This issue of ‘misunderstanding’
reminds us of the Harding et al
5
statement quoted
earlier, concerning the variations in normal wound
appearance, which have to be learnt to avoid
unnecessary intervention.
Bolton et al
36
also point out that maceration may
not be the cause but an effect of a slow to heal
wound. For example, in a venous leg ulcer this is
explained thus:
uncontrolled venous hypertension oedema
exudate maceration.
The underlying cause of oedema compressing
capillaries, leading to disruption of tissue blood
supply, needs to be addressed through effective
graduated compression bandaging.
Maceration — skin pathophysiology
As the stratum corneum (SC) becomes hydrated the
rate of diffusion of water through the SC
increases.
37
Hydration effectively reduces barrier
function in the skin.
It is also recognised that with an increase in
ambient relative humidity (as occurs when peri-
wound skin becomes macerated) there is a decrease
in transepidermal water loss. Additionally, as
hydration of the epidermis increases so does the
incursion or diffusion of materials into the skin.
38
Thus hydration and maceration reduce the skin’s
natural barrier function, permitting the growth
and ingress of pathogens and the inward diffusion
of toxins. Maceration is, therefore, best avoided at
all times.
Conclusion
This article has focused on the causes and effects of
maceration of the skin. It is important to consider
and to differentiate fluid involved in the wound
environment fluid arising from transepidermal
water loss. This should not be with wound exudates
and transudates, although both, to a degree, are
involved in maceration.
This can be mitigated by the careful choice of
dressings and wear times. Exudate from chronic
wounds is inherently different in composition from
acute wound exudate. These differences make
chronic wound fluid a wounding agent in its own
right and therefore potentially more deleterious.
In any exuding wound, particularly chronic
wounds, the possibility of maceration should be
borne in mind at all times. Maceration can delay
healing and indeed lead to enlargement of the
wound. When managing these wounds practition-
ers should consider the possibility of maceration. It
is preferable to avoid it than to treat it.
Future articles will deal with specific wound types
and the physical function of dressings in the con-
trol and reduction of maceration.
Box 1. Summary of the main findings
Maceration can be a complication of any exuding
wound, but particularly chronic wounds
Maceration is caused by excessive amounts of
aqueous fluid — from a variety of sources including
water, urine and exudate — coming in contact with
the skin or wound surface for extended periods
Acute wound exudate differs from chronic wound
exudate. Chronic wound exudate’s properties have led
to it being seen as a wounding agent in its own right
It is important for practitioners to differentiate
between healthy and unhealthy wounds and between
when maceration is caused by water and when by
exudate, transudate or sweating.Transepidermal water
loss can often be controlled by appropriate dressings
278 JOURNAL OF WOUND CARE VOL 11, NO 7, JULY 2002
Fig 2.A healthy leg ulcer showing substantial
re-epithelialisation
... Studies have reported that hard-to-heal DFUs heal poorly due to a prolonged local inflammatory reaction [10][11][12]. This is largely due to persistently high levels of pro-inflammatory cytokines, such as IL-1B and TNF-alpha, present in the wound, leading to enhanced protease expression. ...
... The MMPs, which are initially beneficial to wound healing to initiate the inflammatory phase, now in excess, cause disruption of the healing process [12,13]. These proteases, when exposed to the healthy peri-wound intact skin, may also cause damage to the healthy tissues [10], causing the peri-wound intact skin to be in a pro-inflammatory state, disrupting the normal state of physiology, resulting in disturbing healing of these DFUs. Hence, an aspect of peri-wound intact skin management would be to negate the pro-inflammatory insults from these proteases. ...
Article
Full-text available
Background and Aim The healing of diabetic foot ulcers (DFUs) can be hindered by the susceptibility of the surrounding intact skin to pro‐inflammatory proteases. A conditioned media, known as PTT‐6TM, derived from mesenchymal stem cells found in the lining of red deer umbilical cords, has been formulated to protect the intact peri‐wound skin of DFUs. The aim is to evaluate the clinical effectiveness of PTT‐6TM in managing peri‐wound intact skin in hard‐to‐heal DFUs. Methods Patients with DFUs that persisted for over 3 months were divided into two subgroups. The active wound group received standard‐of‐care treatment protocol followed by PTT‐6TM application around the peri‐wound area, while the maintenance wound group applied PTT‐6TM media over the healed wound site. Results Forty cases were recorded, of which 22 (55%) were included in the active wound group. The majority were male (75%, n = 30) and vast majority had cardiovascular risk factors, including diabetes mellitus (100%, n = 40), hyperlipidemia (82.5%, n = 33), and hypertension (77.5%, n = 31). Most patients had forefoot wounds (80%, n = 32) on the plantar aspect (82.5%, n = 33). The patients in the active wound group had chronic DFUs for a mean of 218 ± 201 days. Of those treated with PTT‐6™ media, 68.4% (n = 13) achieved complete wound healing within a mean duration of 69 ± 50 days. Additionally, most patients in the maintenance wound group remained ulcer‐free at 3 months (91.7%, n = 11) and 6 months (66.7%, n = 6). Conclusion The study results suggest that PTT‐6TM media may serve as an additional treatment modality for enhancing the microenvironment at the peri‐wound intact skin site. This could indirectly facilitate wound healing by preserving the integrity of the peri‐wound intact skin.
... and humidity may compromise the wound bed condition, the integrity of the periwound skin (e.g., maceration) and increase the risk of wound infection. 5,9 Wounds with an excessive bacterial burden may also exhibit unpleasant odour, which can impair patients' quality of life (QoL). 10,11 Venous leg ulcers (VLUs), pressure ulcers/injuries (PU/Is) and diabetic foot ulcers (DFUs) often present with delayed wound healing, which is characterised by increased exudate production and bacterial burden or an increased risk of infection. ...
... Eczema, erythema or maceration of the periwound skin may occur, which further delays or compromises wound healing. 3,9,61 In the current meta-analysis the number of patients with erythema was significantly reduced following the use of silver ion-releasing dressings. ...
Article
Objective Delayed or stalled healing in open wounds can result from persisting chronic inflammation related to infection and/or persistent bacterial colonisation and biofilm. Treatment of hard-to-heal wounds focuses on debridement and exudate management, but also on infection prevention and control. Silver dressings have been evaluated in randomised clinical trials (RCTs); this meta-analysis evaluated the efficacy and safety of a silver ion-releasing foam dressing (Biatain Ag; Coloplast A/S, Denmark) to treat hard-to-heal wounds. Method Literature databases (PubMed and Cochrane Library) were searched for studies on silver ion-releasing foam dressings in the treatment of hard-to-heal wounds. Individual patient data from four RCTs were obtained and included in the meta-analysis. Results Findings showed that treatment with the silver ion-releasing foam dressing was associated with a significantly higher relative reduction in wound area after four (least squares-mean difference (LS-MD): –12.55%, 95% confidence interval (CI): (–15.95, –9.16); p<0.01) and six weeks of treatment (LS-MD: –11.94%, 95%CI: (–17.21, –6.68); p<0.01) compared with controls. Significant benefits were also observed for time to disappearance of odour (hazard ratio: 1.61, 95%CI: (1.31, 1.98); p<0.01), relative reduction of exudate (LS-MD: –5.15, 95%CI: (–7.36, –2.94); p<0.01), proportion of patients with periwound erythema (relative risk (RR): 0.81, 95%CI: (0.69; 0.94); p<0.01), and less pain at dressing removal (LS-MD: –0.35, 95%CI: (–0.63, –0.06); p=0.02). No differences regarding safety outcomes were identified. Conclusion This meta-analysis has demonstrated beneficial outcomes and a good tolerability profile for silver ion-releasing foam dressings in the treatment of moderate-to-highly exuding wounds with delayed healing compared with control dressings.
... A higher occurrence of moisture accumulation was found with the TFA dressing, which could be indicative of inadequate moisture control compared to the SSA dressing. This is clinically significant, as moisture under dressings may contribute to maceration and other complications, or dressing failure [16,17]. Notably, our study was conducted in a region with ambient temperatures typically ranging from 25 to 35 degrees Celsius and humidity levels around 80%, conditions that could influence dressing moisture in this study. ...
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Background Silicone-coated self-adhesive absorbent (SSA) and transparent films with absorbent (TFA) dressings are reportedly effective postoperative knee surgery dressings; however, there have been no direct comparative studies on these two innovative dressings over the hip areas. In this study, we aimed to compare user satisfaction and potential complications between TFA and SSA dressings for the hip area. Methods This prospective randomized controlled trial was conducted at a tertiary hospital. The hip side to receive the polyurethane film with SSA dressing (Mepilex® Border Post-Op) was randomly allocated. The other side of the hip was covered with TFA (OPSITE Post-Op). Participants were scheduled for follow-ups 7 and 14 days after the initial application. Between-group outcomes were compared using a two-sample t-test or Wilcoxon signed-rank test for continuous variables and McNemar’s chi-square test for categorical variables. Results Thirty-two participants (30 − 60 years) without a history of hip surgery were included in the study. The participants were predominantly female, with a mean age of 42.8 years. Pain, difficulties in daily activities, and satisfaction scores were similar between the groups. However, moisture accumulation was significantly higher with the TFA dressing (37.9% vs. 13.8%, p < 0.01), with more dressing failures (34.5% vs. 20.7%, p = 0.016) and complications (37.9% vs. 17.2%, p = 0.012) at the 14-day follow-up than with the SSA dressing. Conclusions SSA dressings are preferable for hip wound care because of better moisture management, fewer dressing changes required, and fewer complications if applied for > 7 days. Both dressings offered high user satisfaction, minimal pain, and minor difficulties in daily activities.
... It is the wound exudate that accomplishes important functions during the healing process, such as moistening the wound and supporting granulation and regeneration of the damaged tissue [81]. The composition of the wound exudate is essentially similar to that of serum [82]. In addition to cellular components such as leucocytes, platelets, macrophages, neutrophils and bacteria, the wound fluid contains cytokines and enzymes (lysozyme or matrix metalloproteinases) as well as ALP [83] and most likely also ADK [84]. ...
Article
Rationale: Tissue regeneration of skin and bone is an energy-intensive, ATP-consuming process that, if impaired, can lead to the development of chronic clinical pictures. ATP levels in the extracellular space including the exudate of wounds, especially chronic wounds, are low. This deficiency can be compensated by inorganic polyphosphate (polyP) supplied via the blood platelets to the regenerating site. Methods: The contribution of the different forms of energy derived from polyP (metabolic energy, mechanical energy and heat) to regeneration processes was dissected and studied both in vitro and in patients. ATP is generated metabolically during the enzymatic cleavage of the energy-rich anhydride bonds between the phosphate units of polyP, involving the two enzymes alkaline phosphatase (ALP) and adenylate kinase (ADK). Exogenous polyP was administered after incorporation into compressed collagen or hydrogel wound coverages to evaluate its regenerative activity for chronic wound healing. Results: In a proof-of-concept study, fast healing of chronic wounds was achieved with the embedded polyP, supporting the crucial regeneration-promoting activity of ATP. In the presence of Ca2+ in the wound exudate, polyP undergoes a coacervation process leading to a conversion of fibroblasts into myofibroblasts, a crucial step supporting cell migration during regenerative tissue repair. During coacervation, a switch from an endothermic to an exothermic, heat-generating process occurs, reflecting a shift from an entropically- to an enthalpically-driven thermodynamic reaction. In addition, mechanical forces cause the appearance of turbulent flows and vortices during liquid-liquid phase separation. These mechanical forces orient the cellular and mineralic (hydroxyapatite crystallite) components, as shown using mineralizing SaOS-2 cells as a model. Conclusion: Here we introduce the energetic triad: metabolic energy (ATP), thermal energy and mechanical energy as a novel theranostic biomarker, which contributes essentially to a successful application of polyP for regeneration processes.
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The pursuit of effective wound healing has prompted a resurgence in the investigation of the therapeutic properties of medicinal plants. This review comprehensively examines ten promising plants and their notable wound-healing attributes. Ranging from the Indian tree Butea monosperma to the common herb Ribwort plantain, each plant offers a distinct array of bioactivities, including antibacterial, antioxidant, and anti-inflammatory effects, all of which are pivotal in the intricate orchestration of the wound healing process. The in-depth exploration of these plants underscores their potential as safe and effective alternatives, or synergistic complements, to conventional wound care products and dressings. Furthermore, the review underscores the significance of standardization, rigorous scientific research, and personalized treatment plans to fully leverage the potential of nature for wound healing. By embracing the synergy between traditional knowledge and scientific rigour, a future where nature’s resources become a cornerstone of wound care, providing accessible, cost-effective solutions for all, is within reach. Major Findings: The use of herbal medicines and plant-based products for wound healing has grown significantly, with several medicinal plants, such as B. monosperma and Calendula officinalis, demonstrating effective wound-healing properties. Regulatory bodies, including the FDA and WHO, oversee the quality and safety of these herbal products, ensuring their efficacy through stringent guidelines and standards.
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Abstract Wound healing is a dynamic physiological process essential for regenerating skin and maintaining coherence in hypodermic tissues. Chitosan-based electrospun nanofibre wound dressings show great promise for expediting the integration of skin and tissues due to their nano-topographic, biodegradable, biocompatible, and antimicrobial properties. However, their moderate bactericidal efficacy and limited mechanical strength hinder their widespread clinical application. The incorporation of specific metal nanoparticles (MNPs) and the functionalization of chitosan have brought attention to their crucial role in wound healing applications, yielding promising results by enhancing antibacterial properties, cell proliferation, cell signaling, and the mechanical robustness of the materials. Chitosan naturally mitigates the cytotoxicity of the incorporated metal nanoparticles within the nanofibers. Chitosan and modified chitosan-based electrospun mats incorporated with metal nanoparticles demonstrate substantial potential for expediting wound healing. This review offers a comprehensive overview of recent advancements in electrospun chitosan-based mats containing MNPs aimed at enhancing wound healing. It covers various aspects, including modification techniques, fabrication methods, wound closure mechanisms, MNP release profiles, histological considerations, addresses existing challenges, and outlines potential future developments.
Chapter
Since biopolymer-based hydrogels are biocompatible, biodegradable, and can absorb and release pharmaceuticals, they have attracted much interest in biomedical applications as a drug delivery method. Drug-loaded hydrogel systems, which offer controlled release over an extended period, can be developed using biopolymer-based hydrogels as efficient carriers for medicinal molecules such as medicines and proteins. Drugs can diffuse through a hydrogel's porous structure, enabling prolonged and targeted delivery to the intended location. Hydrogels based on biopolymers have also proven a potent choice in several medicinal domains, such as treating infectious diseases and cancer. Novel controlled release drug delivery systems (DDS) like hydrogels and nanocomposites have recently received a lot of attention as they attempt to overcome disadvantages of conventional medications such as poor solubility, drug aggregation, low distribution, shortage of selectivity, low bioavailability, and lethal effects. This chapter will discuss the classification of hydrogels, methods of fabrication of hydrogels, and their applications in the drug delivery field. The chapter will also discuss the usage of hydrogel-nanocomposite for sustained drug release based on natural polymers such as xanthan gum, carrageenan, hyaluronic acid, chitosan, gelatin, alginate, and starch.
Article
Objectives An open label, single-centric, post market clinical study was undertaken to evaluate the safety and efficacy of a new antimicrobial wound dressing (VELVERT) as an adjuvant therapy in the treatment of venous leg ulcer (VLU). Methods Patients with VLU of grade C-5 according to CEAP classification and above were evaluated using doppler ultra sound. The efficacy of new antimicrobial wound dressing (VELVERT) was assessed in terms of wound area reduction within a time frame of 60 days and surgeon questioners. Patients were evaluated for VELVERT safety and pain level on a scale of 0-10 Numeric Pain Chart. Presence of micro-organism load was monitored at regular time interval. Results VELVERT treatment was effective as 71.43% reduction in the ulcer area was observed. After 60 days, a total of 9 (45%) patients had complete ulcer closure. A remarkable decrease in the severity of pain was observed with 11 (55%) patients expressing no pain at the EOT. Swab test showed negative result for micro-organism growth. No serious adverse events were observed during the trial. Conclusion The data indicates that VELVERT is an effective treatment for VLUs and showed the potential in the wound care of VLUs.
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The matrix metalloproteinases (MMPs) play a key role in the normal physiology of connective tissue during development, morphogenesis and wound healing, but their unregulated activity has been implicated in numerous disease processes including arthritis, tumor cell metastasis and atherosclerosis. An important mechanism for the regulation of the activity of MMPs is via binding to a family of homologous proteins referred to as the tissue inhibitors of metalloproteinases (TIMP-1 to TIMP-4). The two-domain TIMPs are of relatively small size, yet have been found to exhibit several biochemical and physiological/biological functions, including inhibition of active MMPs, proMMP activation, cell growth promotion, matrix binding, inhibition of angiogenesis and the induction of apoptosis. Mutations in TIMP-3 are the cause of Sorsby’s fundus dystrophy in humans, a disease that results in early onset macular degeneration. This review highlights the evolution of TIMPs, the recently elucidated high-resolution structures of TIMPs and their complexes with metalloproteinases, and the results of mutational and other studies of structure–function relationships that have enhanced our understanding of the mechanism and specificity of the inhibition of MMPs by TIMPs. Several intriguing questions, such as the basis of the multiple biological functions of TIMPs, the kinetics of TIMP–MMP interactions and the differences in binding in some TIMP–metalloproteinase pairs are discussed which, though not fully resolved, serve to illustrate the kind of issues that are important for a full understanding of the interactions between families of molecules.
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The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.
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We have studied the cell population, neutrophil bactericidal activity, protein type and the content of human wound exudate which accumulates under an adhesive polyurethane film dressing (Op-Site∗). The cell type and numbers of cells in the exudate are typical of an inflammatory response, and the protein content of the exudate is virtually indistinguishable from that of plasma. Also, the neutrophils present in the exudate killed Staphylococcus aureus at a rate similar to normal whole blood, indicating that there would be a minimal risk of clinical infection under Op-Site.
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Fluid obtained from chronic and acute wounds were examined for the presence of fibronectin, α1-antitrypsin, and proteinases capable of degrading both proteins. Immunoblot analysis of fluids from ten chronic wounds revealed that fibronectin and α1-antitrypsin were degraded in nine of ten samples. In contrast, both fibronectin and α1-antitrypsin were intact in acute wound fluids. The degradation of the inhibitor and fibronectin occurred in the same wound fluids, and these two events correlated perfectly. Chronic or acute wound fluid proteins were coupled to benzamidine Sepharose 6B beads and incubated with fibronectin or α1-antitrypsin. Chronic wound fluid proteins degraded fibronectin in the presence of ethylenediaminetetraacetate, leupeptin, cystatin, and pepstatin but not in the presence of phenylmethylsulfonyl fluoride. Acute wound fluids and normal human serum did not contain enzymes capable of degrading fibronectin. These data suggest that serine proteinases are responsible for fibronectin degradation in chronic wound fluids. Chronic wound fluids that contained degraded α1-antitrypsin also contain proteinases capable of degrading α1-antitrypsin from human serum. Acute wound fluids and normal human serum did not contain enzymes capable of degrading α1-antitrypsin. The inhibitor from acute wound fluids bound to one of its targets, trypsin. In contrast, the fragment(s) of α1-antitrypsin from chronic wound fluids did not bind trypsin. Chronic wounds associated with degraded fibronectin and the inhibitor contained ten- to forty-fold more elastase activity than acute wounds. The degradation of fibronectin by chronic wound fluid enzymes was inhibited by α1-antitrypsin in a dose-dependent manner. Collectively, these results demonstrate that there are enzymes in chronic wounds that perturb the function of α1-antitrypsin and allow fibronectin degradation by uninhibited serine proteinases.
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The role of matrix-degrading enzymes, particularly plasminogen activators and matrix metalloproteinases, in the acute wound healing response has been the focus of many scientific studies. Only recently have these classes of endogenously produced proteinases been studied with regard to their involvement in the chronic wound environment. Using both in situ histologic zymography and immunohistochemical techniques, we examined the distribution of plasminogen activators and matrix metalloproteinase in the granulation tissue of pressure ulcers. Using in situ histologic zymography, urokinase was found to be the predominant plasminogen activator activity in the chronic wound granulation tissue, with little or no tissue-type plasminogen activator activity. These results were confirmed with the use of immunohistochemical techniques. In contrast, tissue-type plasminogen activator was found to be constitutively expressed in normal skin. Levels of matrix metalloproteinases were also found to be elevated in the granulation tissue of pressure ulcers. Immunohistochemical localization of leukocyte-associated proteinases (PMN elastase and cathepsin G) suggested a highly inflamed environment within the pressure ulcer granulation tissue. These results suggest a highly proteolytic environment within the chronic wound.
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Two enterotoxigenic strains of Staphylococcus aureus were examined for their ability to produce a number of extracellular enzymes at various water activity (alphaw) levels. Supernatant, dialyzed culture media were analyzed for total and relative levels of enzyme activity. With the exception of protease, enzyme activity was greatest in spent media obtained from cultures grown at 0.996 alphaw, the highest level tested. Enzyme activity in spent media from an enterotoxin B-producing strain was generally more sensitive to alphaw reduction than activity from an enterotoxin A-producing strain. Unlike the other enzymes assayed, acid and alkaline protease activities were greatest when the organism was grown at 0.94 alphaw.
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The clinical effects of occlusive dressings on wound healing are well documented. However, the underlying biologic mechanisms associated with moist healing are not well understood. Experimental studies and clinical experience have shown enhanced eschar and clot removal, re-epithelialization, and collagen synthesis under occlusion, suggesting the possibility of elevated activities of proteinases and other effectors, e.g., growth factors, in the moist wound environment. To gain an insight into the biology of early wounds under occlusion, we have carried out biologic and biochemical analyses on fluids from occluded full- and partial-thickness wounds. Metalloproteinase activities were detected in the wound fluid samples. When applied to cultured dermal fibroblasts, mitogenic activity was observed with fluids from full-thickness wounds. Wound fluid-stimulated accumulation of urokinase-type plasminogen activator by fibroblasts was also observed in a time-dependent manner. Stimulation of metalloproteinase accumulation by fibroblasts was also observed. We have further demonstrated the presence of platelet-derived growth factor-like and basic fibroblast growth factor-like factors in wound fluid by antibody neutralization of their biologic activities. Proteinase presence and proteinase stimulatory activity of wound fluid retained in the occluded wound may contribute to an enhanced proteolytic environment in these wounds in comparison to non-occluded "dry" wounds. The presence of growth factors and the potential abilities of proteinases to activate latent growth factors and generate chemotactic peptides through connective tissue breakdown may also contribute to the enhanced healing of occluded wounds.
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Clinical and laboratory studies were made to compare the water vapour permeability, bacteriological properties and clinical performance of polythene and polytetrafluoroethylene fabric (GORE-TEX) bags in the treatment of hand burns. Polythene bags are virtually impermeable to saline, whereas GORE-TEX bags containing silver sulphadiazine cream show a water vapour permeability of 0.53 ml/cm2/day, resulting in a 30 per cent weight reduction of added water after 48 h. Clinically, hand maceration and accumulation of exudate are significantly reduced in hands treated in GORE-TEX bags. The mean daily volume of accumulated exudate for GORE-TEX bags was 37 ml compared to 83 ml for polythene (P less than 0.01). When adjusted for the percentage area of the hand surface burned, this reduction remained significant (P less than 0.005). A tendency for less pain and better hand movement was noted with GORE-TEX bags. There were no significant differences in rate of healing or bacterial colonization of the burned hand between the two type of bags. GORE-TEX bags prevent skin maceration and accumulation of exudate, allowing ease of burn assessment and improved hand function. They are also durable and non-slip, thus increasing patient independence.
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We have isolated the lowest region of human and pig stratum corneum as an integral layer which we have termed the stratum compactum. This preparation is resistant to disruption by enzymes, 6 M urea, Triton X-100 and solvents. Our evidence suggests that all cells of the stratum corneum may be equally permeable to aqueous soluble materials but that penetration of materials through the corneum depends on the state of cohesion between cells and of the organization of intercellular lipid species. As the cells move up towards the outside of the stratum corneum the cohesive forces are reduced due to desmosome degradation and lipid modifications with ultimate dyshesion and sloughing of individual cells.