A new approach to understanding the biology of wound healing

Date:
September 15, 2020
Source:
Thomas Jefferson University
Summary:
Researchers use discarded wound dressings as a novel and
non-invasive way to study the mechanisms that promote healing.



FULL STORY ==========================================================================
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."

========================================================================== Story Source: Materials provided by Thomas_Jefferson_University. Original written by Karuna Meda. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Ignacia Fuentes, Christina Guttmann-Gruber, Birgit Tockner,
Anja Diem,
Alfred Klausegger, Glenda Cofre'-Araneda, Olga Figuera,
Yessia Hidalgo, Pilar Morande', Francis Palisson, Boris
Rebolledo-Jaramillo, Mari'a Joao Yubero, Raymond J. Cho, Heather
I. Rishel, M. Peter Marinkovich, Joyce M.

C. Teng, Timothy G. Webster, Marco Prisco, Luis H. Eraso,
Josefina Pin~on Hofbauer, Andrew P. South. Cells from discarded
dressings differentiate chronic from acute wounds in patients with
Epidermolysis Bullosa.

Scientific Reports, 2020; 10 (1) DOI: 10.1038/s41598-020-71794-1 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200915152443.htm

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