Repair scars with transplanted hair follicles

In a new study involving three volunteers, skin scars began to look more like normal skin
after receiving a hair follicle transplant.
The scarred skin gave birth to new cells and blood vessels, remodeled the pattern of collagen to restore health, and even expressed genes
found in healthy scar-free skin.

The discovery could lead to better treatments for scars on the skin and in the body, offering hope to patients with large scars that impair organ function and lead to disability
.

Lead author Dr Claire Higgins, from Imperial College's Department of Bioengineering, said: "After leaving a scar, the skin never really returns to its pre-wound function, and so far all efforts to reshape the scar have had little
effect.
Our findings set the stage for exciting new therapies that can even rejuvenate mature scars and restore the function of
healthy skin.
”

The study was published in the journal Nature Regenerative Medicine
.

Hope in your hair

Scar tissue on the skin lacks hair, sweat glands, blood vessels, and nerves, which are essential
for regulating body temperature and sensing pain, and other sensations.
Scars can also affect movement and can cause discomfort and emotional distress
.

Compared to scar tissue, healthy skin undergoes constant remodeling
of hair follicles.
Hairy skin heals faster and scars less than hairless skin — and hair transplants have previously been shown to help wounds heal.

Inspired by this, the researchers hypothesized that transplanting growing hair follicles into scar tissue might induce scar self-transformation
.

To test their hypothesis, researchers at Imperial College London, in collaboration with Francisco M.
Dr.
Jiménez, co-author, is the Chief Hair Transplant Surgeon at the Mediteknia Clinic and an Associate Professor
at the Fernando Pessoa Canaria University in Gran Canaria, Spain.
In 2017, they transplanted hair follicles into mature scars on the scalps of three participants
.
The researchers selected the most common type of scar, called normal trophic scars, which usually form
after surgery.

They biopsied the scar 3 mm thick and microscopic imaging before transplantation, and then again at 2, 4 and 6 months after transplantation
.

The researchers found that these follicles inspired structural and genetic changes in the scar, giving it healthy, uninjured skin
.

Dr Jiménez said: "In high-income countries alone, about 100 million people are scarred
by surgery every year.
The global incidence of scarring is much higher, including extensive scarring from burns and post-traumatic scars
.
Our research opens up new avenues for treating scars and may even change the way we prevent
scars.
”

Architect of skin

After transplantation, hair follicles continue to produce hair and induce repair of the skin layer
.

Scars cause the outermost layer of the skin – the epidermis – to thin, making it prone to tearing
.
Six months after transplantation, the thickness of the epidermis doubled and cell growth increased, about the same
thickness as uninjured skin.

Further down is the dermis, which is filled with connective tissue, blood vessels, sweat glands, nerves, and hair follicles
.
After the scar matured, the cells and blood vessels in the dermis layer decreased, but after transplantation, the number of cells doubled after six months, and the number of blood vessels reached a level
close to healthy skin after four months.
This suggests that follicles stimulate the growth of new cells and blood vessels in the scar that cannot grow
without help.

Scars also increase the density of collagen fibers, a major structural protein in the skin, which neatly aligns them and makes scar tissue harder
than healthy tissue.
Hair transplants reduce the density of the fibers, allowing them to develop a healthier "basket weaving" pattern that reduces hardness – a key factor
in causing tears and discomfort.

The authors also found that after transplantation, scar expressed 719 genes differently
than before transplantation.
More genes are expressed to promote cell and blood vessel growth, while fewer genes are expressed to promote the scarring process
.

A multi-pronged approach

Researchers aren't sure how transplantation
promotes this change.
In their study, the presence of hair follicles in scars was aesthetically acceptable because scars were on the
scalp.
They are now working to uncover the underlying mechanisms so they can develop a therapy that reshapes scar tissue into healthy skin without the need to transplant hair follicles and grow hair fibers
.
They can then test their findings on hairless skin or on organs such as the heart, which scars after a heart attack and the liver, which scars fatty liver and cirrhosis
.

"This work has clear applications in restoring confidence, but our approach is not limited to beauty, as scar tissue causes problems
in all our organs," Dr.
Higgins said.

"While current treatments for scars, such as growth factors, focus on the single factor that causes scarring, our new approach is multifaceted, as hair follicles may provide multiple growth factors at the same time, reshaping scar tissue
.
" This provides further support for the use of treatments such as hair transplantation, which alter the structure and gene expression of the scar, thereby restoring the scar's function
.
”

This work was funded
by the Medical Research Council and the Engineering and Physical Sciences Research Council (part of UKRI).

Journal Reference:

1. Magdalena Plotczyk, Francisco Jimé nez, Summik Limbu, Colin J.
   Boyle, Jesse Ovia, Benjamin D.
   Almquist, Claire A.
   Higgins.
   Anagen hair follicles transplanted into mature human scars remodel fibrotic tissue.
   npj Regenerative Medicine, 2023; 8 (1) DOI: 10.
   1038/s41536-022-00270-3