Hyaluronic Acid as a Treatment Option for Pressure Ulcers

Hyaluronic Acid as a Treatment Option for Pressure Ulcers

BRIEF COMMUNICATION
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Hyaluronic Acid as a Treatment
Option for Pressure Ulcers
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Key words: pressure ulcers, hyaluronic acid, wound healing
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Address correspondence to:
Concepción Ruiz
Faculty of Health Sciences
University of Granada
Avda de Madrid s/n
18071-Granada (Spain)
[email protected]
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From the 1Department of Nursing,
Faculty of Health Sciences,
University of Granada, Granada,
Spain; 2Neuroscience Institute,
University of Granada, Granada,
Spain
Abstract: Introduction. Health care professionals are constantly seeking
novel approaches to treat pressure ulcers because of the impact they have
on patient quality of life and health, as well as the costs associated with
treating them. Methods. A review of the literature from 2002-2012 was
conducted on the clinical usefulness of hyaluronic acid in tissue regeneration. Reports suggest that the therapeutic use of hyaluronic acid favors
tissue regeneration by modulating the hydration and osmotic balance. Results. Different studies show that hyaluronan and derived-hyaluronic acid
products are safe and free of adverse effects. Furthermore, a few studies
examine the hyaluronic acids repercussions in pressure ulcer treatment.
Conclusion. Reports suggest that this molecule could be successfully used
to treat pressure ulcers in association with conventional measures.
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WOUNDS 2013;25(12):328-332
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Javier Ramos-Torrecillas, PhD1; Elvira De Luna-Bertos, PhD1;
Lourdes Díaz-Rodríguez, PhD1; Olga García-Martínez, PhD1;
Laura Rodríguez-Pérez, RN1; Concepción Ruiz, PhD1,2
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Disclosure: The authors disclose
no financial or other conflicts of
interest.
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ressure ulcers (PUs) are skin lesions that may involve the epidermis
and deeper layers of the skin, sometimes even causing damage to
muscle or bone. Triggering factors include an increase in capillary
pressure at skin level as a consequence of the action of 2 opposing forces,
as in the case of pressure on a bone protuberance.1 Pressure ulcers compromise the health and quality of life of patients and entail high economic
costs. Patients with a single PU are 3.5 to 5 times more likely to stay in
the hospital than patients without an ulcer, and the development of novel
approaches is of great interest to health care professionals, especially the
nurses, who often treat them.2
Pressure ulcers are currently treated with a moist environment, which
high-level evidence has proved effective in reducing healing time.3 Hyaluronic acid is one of a group of molecules proposed to participate in the
pathophysiological mechanisms underlying wound healing.4 More recent
studies have shown that treatment with hyaluronic acids and their derivatives have an important role in the regeneration of various tissues, such as
periodontal, bone, adipose, or cartilage regeneration.5-7
The objective of this study was to review published reports on the clinical usefulness of hyaluronic acid in tissue regeneration and PU healing.
Ramos-Torrecillas et al
Results
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•The objective of this study was to review published
reports on the clinical usefulness of hyaluronic acid
in tissue regeneration and pressure ulcer healing.
•The key characteristic of this molecule is its high
hydroscopicity, which serves to regulate tissue hydration and osmotic balance.
•It is also water soluble, enabling the formation of an
easily handled and applied gel.10
a number of receptors, activating a cascade of signals
that influence gene migration, proliferation, and expression at the extracellular matrix level.15
Hyaluronic acid and its sodium salts are used for
wound healing. One explanation for its positive effect
is that collagen deposited by fibroblasts is a key factor
in tissue reconstruction, and hyaluronic acid has been
found to stimulate fibroblast proliferation in both in
vivo and in vitro studies.16 There is also evidence of
an increase in extracellular matrix remodeling and an
improved organization of collagen deposits after the
application of hyaluronic acid.17 Moreover, the degradation products of hyaluronic acid are proangiogenic
and can modulate the production of hyaluronic acid
by fibroblasts, which is regulated by a large number of
growth factors.18 Finally, hyaluronic acid also favors tissue regeneration by increasing keratinocyte proliferation and mobility.19,20
A major advantage in the clinical setting of hyaluronic acid and its salts is that it has very few adverse
effects, with only isolated reports of inflammation and
hypersensitivity.21-23 Hyaluronic acid is currently considered a useful resource in tissue regeneration.5
Pressure ulcers. Pressure ulcers are lesions of ischemic origin on the skin and underlying tissue with
loss of cutaneous substance. They are produced by
prolonged pressure or friction between a hard surface
of the patient and a hard surface in contact with the
patient. Care guidelines in numerous institutions classify 3 primary types of risk factors for PU formation:
pressure, friction, and shear.24 Pressure ulcers are most
frequently observed at bone protuberances, when the
soft tissue has been compressed against an external
surface. Tissue hypoxia produces rapid tissue degeneration in the area, which can range widely between a
mild skin reddening and deep ulcers involving muscle
or even bone.1,3
The prevalence of PUs in Spain increased between
the first National PU Survey in 200125 and the second in
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Hyaluronic acid is a natural biopolymer with a highly
preserved molecular structure among mammal species.
It was first reported in 1934 and was subsequently synthesized in the laboratory.8 It is a natural polymer of disaccharides, which are composed of alternating D-glucuronic acid and D-N-acetylglucosamine, linked together
via alternating β-1,4 and β-1,3 glycosidic bonds. One of
the components of the extracellular matrix, hyaluronic
acid is present in skin, cartilage, bone, and brain, among
other tissues. It has proved valuable in neurosurgery
and dermatology because hyaluronic acid and degradation products can modulate wound healing.8 Numerous studies have demonstrated the usefulness of hyaluronic acid in skin lesions and cartilage defects, in glial
cell culture, and in the regeneration/increase of sperm
motility.8 Over the past few years, there has been a
considerable increase in the use of hyaluronic acid in
aesthetic plastic surgery.9 Physiologically, the key characteristic of this molecule is its high hydroscopicity,
which serves to regulate tissue hydration and osmotic
balance. It is also water soluble, enabling the formation
of an easily handled and applied gel.10 In recent years,
hyaluronic acid and its sodium salt have been applied
for multiple clinical purposes.11,12
Keypoints
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Literature searches were carried out using the dialog interface in the following databases: PubMed and
CINAHL. Databases were searched from 2002 through
2012 for human studies. The following key words were
covered in the search strategy: “hyaluronic acid,” “pressure ulcers,” “pressure sores,“ “hyaluronic acid and
pressure ulcers,” and “hyaluronic acid and pressure
sores.” Titles and abstracts identified by the literature
searches were read and reviewed. Those not appearing
to meet key words were excluded and the others were
reviewed in full.
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Material and Methods
Discussion
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Usefulness of hyaluronic acid and its sodium salt
in tissue regeneration. The usefulness of hyaluronic
acid and its derivatives in tissue regeneration, tissue
engineering, epidermal diseases, ophthalmic surgery,
and plastic surgery is well documented.9,11-14 Although
the action mechanism of this molecule in tissue regeneration has not been fully elucidated, effects have generally been attributed to its lubricating, hydroscopic,
and homeostatic properties.15 It can also interact with
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Conclusion
More effective treatment options are required for
PUs due to their elevated prevalence, negative impact
on quality of life of patients, and high associated costs.
There is wide scientific evidence on the positive role
of hyaluronic acid and its sodium salts in tissue regeneration and wound healing. It maintains wound hydration and may neutralize the excess hyaluronidase in
lesions and eliminate free radicals. High efficacy of hyaluronic acid was proven, particularly in the treatment
of diabetic ulcers. Its use when treating PUs resulted in
reduction of the ulcer size and a good tolerability and
efficacy, but few data are available on its use to treat
these wounds. Further research is warranted into the
utilization of hyaluronic acid and related substances
for PUs.
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200526 from to 8.34% to 9.11% of primary care patients
receiving home care; 8.81% to 8.91% of hospitalized
patients; and 7.6% to 10.9% of patients in residences
for the elderly. This high prevalence is associated with
major economic repercussions, as detailed in numerous studies worldwide.27,28
The moist healing procedure has demonstrated the
best outcomes to date.29,30 However, there have been
wide investigations on alternative treatments to deliver
more rapid tissue regeneration, including the utilization of growth factors and platelets and of autologous
growth factor- and platelet-rich plasma.31-35
Pressure ulcers and hyaluronic acid. Hyaluronic
acid has long been used to regenerate damaged tissue, but few data are available on its use to treat PUs.
A biopsy study found significantly lower hyaluronic
acid levels in tissue samples from chronic PUs than in
samples from open skin wounds, and lower levels in
both compared to healthy tissue samples.15 This may
be related to depolymerization of hyaluronic acid due
to the higher hyaluronidase activity and presence of
reactive oxygen species (free radicals) in the inflammatory response.36 Further studies reported the use
of sodium hyaluronate and iodine complex in patients
with diabetic foot problems. This treatment was effective in the majority of the patients with diabetes. The
local treatment did not produce side effects or allergic reaction.37 Barrois et al38 investigated the efficacy
and tolerability of hyaluronan (hyaluronic acid) treatment over 3 weeks in 21 patients with PUs. The results
showed tolerability and efficacy of this treatment was
good or very good, depending on the reduction of surface area, the presence of granulation tissue, and the
decrease of fibrous tissue. A recent study determined
the usefulness of combining hyaluronic acid and argentic sulphadiazine in the treatment of PUs.39 Paghetti et
al39 found that improvement or complete healing of
PUs was observed in 67% of patients at early followup (10 days), increasing to 76% and 87% at 20 and 35
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•Collagen deposited by fibroblasts is a key factor in
tissue reconstruction, and hyaluronic acid has been
found to stimulate fibroblast proliferation in both in
vivo and in vitro studies.16
•A major advantage in the clinical setting of hyaluronic acid and its salts is that it has very few adverse effects, with only isolated reports of inflammation and hypersensitivity.21-23
days, respectively.39 Hyaluronic acid has also been used
as an active wound dressing.40 Zavan et al40 described
the utility of porous nanoparticles of hyaluronan enriched with growth factors in the treatment of PUs.
Other studies showed the efficacy of a 3-dimensional,
polymerized hyaluronic acid as a biologic medicated
dressing.41,42 Recently, a new formulation of hyaluronic
acid (lysine-hyaluronate) has been studied to treat decubitus ulcers. The results obtained in a double-blind
randomized study showed a greater reduction of the
ulcer size treated with lysine-hyaluronate vs the commonly used sodium hyaluronate.43
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Keypoints
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