Using transplanted hair follicles, scientists from Imperial College London have demonstrated the possibility of triggering scar tissue to behave like uninjured skin, raising hope for future scar treatments.
The authors of the new study, published in Nature Regenerative Medicine, pointed out that scar tissue "lacks hair, sweat glands, blood vessels, and nerves, which are vital for regulating body temperature and detecting pain and other sensations". They added that scarring can also "impair movement as well as potentially causing discomfort and emotional distress".
Scarring imposes an enormous burden on individuals and society, with an estimated 100 million people per year acquiring scars in high-income countries alone, primarily as a result of surgeries. The global incidence of scars is much higher and includes extensive scarring formed after burn and traumatic injuries.
Despite the substantial impact of skin scarring on patients and the healthcare system, there is a lack of strategies to prevent scar formation or to remodel mature scars. Traditional strategies to reduce scar formation, including incisions along Langer's lines, deep sutures to bring skin edges together, and dressings that offload tension from the wound, lack large-scale clinical studies to prove their effectiveness, the authors emphasised. So too do strategies to improve scar appearance, such as laser, dermabrasion, and micro-needling.
Dr Claire Higgins, Imperial College London Department of Bioengineering, and lead author, explained: "After scarring, the skin never truly regains its pre-wound functions, and until now all efforts to remodel scars have yielded poor results."
Compared with scar tissue, healthy skin undergoes constant remodelling by the hair follicle, and it heals faster and scars less than non-hairy skin.
Having acknowledged that hair transplants had previously been shown to aid wound healing, the researchers hypothesised that transplanting growing hair follicles into scar tissue might induce scars to remodel themselves.
Architectural and Genetic Shifts
To investigate this hypothesis, the UK researchers teamed up with Dr Francisco Jiménez, a hair transplant surgeon at the Mediteknia Clinic and associate research professor at University Fernando Pessoa Canarias, in Gran Canaria, Spain, and established a pilot clinical study involving three male patients with mature (aged at least 4 years) and wide scars (at least 5 mm) formed post-surgically on occipital scalps after follicular unit transplantation (FUT) surgery. The authors pointed out that after this procedure most patients heal with narrow scars; however, around 1 in 7 (14.7%) heal with post-operating scar widening, which they explained that they used in their study.
The researchers transplanted hair follicles into the mature scars on the scalp of three participants in 2017. They selected the most common type of scar (normotrophic) that usually forms after surgery, but excluded keloid and hypertrophic scars which they said were of "more complex pathology".
They took and microscope imaged 3-mm thick biopsies of the scars just before transplantation, and then again at 2, 4, and 6 months afterwards, and found that the follicles inspired "profound architectural and genetic shifts" in the scars towards a profile of healthy, uninjured skin, and behaved more like uninjured skin treatment with hair follicle transplants.
The scarred skin harboured new cells and blood vessels, remodelled collagen to restore healthy patterns, and expressed genes found in healthy unscarred skin.
Hair follicle transplantation "induced an increase in the epidermal thickness, interdigitation of the epidermal dermal junction, dermal cell density, and blood vessel density", they said. Specifically, at 6 months post-transplant, the epidermis had doubled in thickness alongside increased cell growth, bringing it to around the same thickness as uninjured skin. In the dermis the number of cells had doubled at 6 months, with the number of vessels having reached nearly healthy-skin levels by 4 months.
"This demonstrated that the follicles inspired the growth of new cells and blood vessels in the scars, which are unable to do this unaided," said the authors.
The hair transplants reduced the density of the fibres, which allowed them to form a healthier, 'basket weave' pattern, which reduced stiffness – a key factor in tears and discomfort, explained the authors.
In addition, after transplantation the scars "expressed 719 genes differently to before", with genes that promote cell and blood vessel growth being expressed more, whilst genes that promote scar-forming processes were expressed less.
New Scar Treatment Avenues
The results showed that anagen hair follicles can attenuate the fibrotic phenotype, providing new insights for developing regenerative approaches to remodel mature scars, the authors said.
The study findings "lay the foundation" for exciting new therapies that can rejuvenate mature scars and restore the function of healthy skin, enthused Dr Higgins.
Dr Jiménez concurred. "Our work opens new avenues for treating scars and could even change our approach to preventing them," he stressed.
The researchers admitted that they were unsure precisely how the transplants facilitated such a change, and they are now working to uncover the underlying mechanisms so they can develop therapies that remodel scar tissue towards healthy skin, without requiring transplantation of a hair follicle and growth of a hair fibre.
The findings could lead to better treatments for scarring both on the skin and inside the body, leading to hope for patients with extensive scarring, which can impair organ function and cause disability.
Dr Higgins highlighted that their work has "obvious applications in restoring people's confidence", but their approach "goes beyond the cosmetic" as scar tissue can cause problems in all our organs.
In the future they hope to test their findings on non-hairy skin, or on organs like the heart, which can suffer scarring after infarction, and the liver, which can suffer scarring through fatty liver disease and cirrhosis, they pointed out.
Funding for the study was provided by the Medical Research Council and Engineering and Physical Sciences Research Council.
