A new approach to understanding the biology of wound healing -- Researchers use discarded wound dressings as a novel and non-invasive way to study the mechanisms that promote healing.
Thomas Jefferson University – September 15,
2020 -- Our bodies frequently heal wounds, like a cut or a scrape, on their
own. However patients with diabetes, vascular disease, and skin disorders,
sometimes have difficulty healing. This can lead to chronic wounds, which can
severely impact quality of life. The management of chronic wounds is a major
cost to healthcare systems, with the U.S alone spending an estimated 10-20 billion
dollars per year. Still, we know very little about why some wounds become
chronic, making it hard to develop effective therapeutics to promote healing.
New research from Jefferson describes a novel way to sample the cells found at
wounds -- using discarded wound dressings. This non-invasive approach opens a
window into the cellular composition of wounds, and an opportunity to identify
characteristics of wounds likely to heal versus those that become chronic, as
well as inform the development of targeted therapies.
The study was published in Scientific
Reports on September 15th.
"Studying wound healing in humans
is very challenging, and we know very little about the process in humans,"
says Andrew South, PhD, Associate Professor in the Department of Dermatology
and Cutaneous Biology and one of the lead authors of the study. "What we
do know is from animal studies, and animal skin and the way it heals is very
different from human skin."
Dr. South and his lab study a group of
inherited skin diseases called epidermolysis bullosa (EB), where wound healing
is severely impaired. Patients, often from birth, suffer from blisters and
lesions that are slow to heal, and some become chronic. In a subset of
patients, chronic wounds are at high risk of developing into aggressive skin
cancer. At this time, it is very difficult to predict which wounds in a given
patient will heal, and which won't. Being able to sample the wounds is a key to
understanding the mechanisms behind healing.
"Performing a biopsy to sample the
cells in the wound would help us understand the differences between these
wounds," says Dr. South "But biopsy in these patients is extremely
painful and could delay healing of the wound even further. On the other hand,
collecting these bandages that are just going to be thrown away, it poses no
harm to the patient, and can be applied to a variety of conditions where wounds
don't heal properly."
The researchers, which included
collaborators in Chile and Austria, collected and analyzed 133 discarded wound
dressings from 51 EB patients. Both acute and chronic wounds were sampled, with
acute defined as present for 21 days or less, and chronic as present for more
than 3 months.
"Previous studies had used wound
dressings or bandages to collect fluid and look at what proteins are in
there," says Dr. South. "But no one has actually looked at what cells
are present. Applying the techniques our lab frequently uses, we were able to
isolate viable or living cells from the dressings."
The researchers recovered a large number
of cells from the dressings, often in excess of a 100 million. The larger the
wound, and the more time a dressing was on a wound, the more number of cells
were recovered.
The researchers then characterized the
cells to see what type of cells are present at the wound. They detected a
variety of immune cells including lymphocytes, granulocytes or neutrophils, and
monocytes or macrophages. When comparing dressings from acute and chronic
wounds, they found a significantly higher number of neutrophils at chronic
wound sites. Neutrophils are the first line of defense in our immune system,
and when a wound starts to form, they're the first ones to arrive at the scene.
"Previous findings from animal
studies and protein analysis of human wound dressings had supported the idea
that when neutrophils hang around longer than they should, that stalls the
healing process and can lead to chronicity," says Dr. South. "Our
findings support that theory more definitively, by showing that chronic wounds
are characterized by higher levels of neutrophils."
These findings give more insight into wound
healing, and could help develop therapies that promote the process; for
instance, those that neutralize excess neutrophils, or recruit macrophages, the
immune cells that begin the next stage in healing after neutrophils.
The researchers now plan to expand on
their technique, by further analyzing the individual cells collected from the
wound dressings, and the genetic material inside them. "Currently we're
working with colleagues in Santiago, Chile on collecting dressings from EB
patients over a period of time," says Dr. South. "This allows us to
follow patients longitudinally, and observe a wound and how its cellular
composition changes as it heals or doesn't heal."
The team hopes that this will reveal
genetic markers that can predict healing or chronicity.
"This method of sampling could be
an alternative to bothersome swabs or blood draws, which are especially hard to
do in newborns," says Dr. South. "Since we know EB can present at
birth, this technique could give us really early insight into the how severe
the disease might be."
While the current study focuses on EB,
Dr. South and his colleagues hope that this technique can be applied to a
variety of other conditions, such as diabetic foot ulcers and vascular leg
ulcers.
"The field of wound healing has
been crying out for a better understanding of what drives a chronic
wound," says Dr. South. "This technique could be transformative, and
eventually help patients live more comfortable and healthy lives."
https://www.sciencedaily.com/releases/2020/09/200915152443.htm
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