Getting to the root of skin healing

18 April 2023

skin, wound, healing

The roots of a single tree can transform a barren patch of forest floor into a thriving subterranean ecosystem. A tree’s roots exude chemicals and signalling molecules that remodel the soil to stimulate further growth.In this way, arborists and foresters reestablish the ecological function of degraded landscapes. Similarly, hair transplant surgeons remodel the terrain of the human scalp, planting hair follicles like trees in a forest. Hair transplantation augments hair loss caused by baldness or skin injury. Besides the cosmetic advantages, researchers are discovering that transplanted hair follicles also remodel scarred skin to create functional tissue, much like transplanted trees transform previously barren soil.

In a recent study published in npj Regenerative Medicine, Claire Higgins, a professor of bioengineering at Imperial College London, and her team performed a pilot clinical study in which they transplanted hair follicles into human skin scars. “Hair transplant surgeons already use this for scarring on the head or face,” Higgins said. “They told us that when they do eyebrow transplants, the scar tissue around it will also look better.” Higgins and her team decided to take a deeper look below the skin’s surface to understand how follicle transplants change the architecture of scarred skin tissue.

George Cotsarelis, a physician, professor, and chair of dermatology at the University of Pennsylvania, who was not involved in this study, explained that skin injury—due to burns, surgical incisions, or traumatic injuries—induces fibrotic scarring, despite the well-orchestrated cascade of biochemical and cellular mechanisms that drive wound repair. Fibrotic scars have pathological features, including a thin epidermis, thick connective tissue, and a low density of blood vessels and nerves, which extend far below the surface of the skin. “There are huge functional consequences to some types of scarring,” Cotsarelis said. Although scar tissue is a byproduct of repair, it can severely limit skin function, causing contraction, pain, reduced sensation, and restricted mobility.

To learn more, listen to this Science Philosophy in a Flash mini podcast, “A Surprising Way to Repair Scar Tissue”
Higgins and her team recruited three patients from a hair transplantation clinic who underwent routine hair follicle transplantation to conceal surgical scalp scars from previous transplant procedures. The hair follicles were taken from the patients’ own scalps and transplanted during anagen—the active phase of hair growth characterised by stem cell proliferation and migration, and the release of signalling molecules. Higgins’ team obtained skin biopsies from these scars and compared the tissue before and up to six months after anagen hair follicle transplantation.

They found that the treated tissue resembled healthy skin, both in terms of physical make-up and gene expression. Transplanted anagen follicles induced scar tissue remodeling and reduced pro-fibrotic cytokines. Higgins’s team proposed that epithelial stem cell migration from the hair follicles to the scar tissue and growth factors secreted from the follicles underly this improvement. This is not entirely surprising given that healthy skin is consistently remodeled during hair follicles’ active growth phase, including an increase in skin thickness, nerves, and blood vessels.

“This is the first clear demonstration that you can transplant hair follicles into a mature scar and get some kind of outcome,” said Matthew Hardman, a professor and chair of wound healing at the University of Hull, who was not involved in this study. He explained that skin injuries that occur during the anagen phase of hair growth heal twice as quickly as when follicles are in their resting stage. “Stem cells are activated, and growth factors are being produced. It’s the phase of the hair cycle that is most conducive to promoting healing.” Skin injury causes cells to stream out from hair follicles to repair the wound, recapitulating the role of hair follicles during skin embryogenesis. In this way, they act as an anchor and reservoir to support skin development and repair.

Similarly, a developing tree’s embryonic root bores its way into the soil during seed germination. From that moment of first contact, it becomes the tree’s anchor in the subterranean environment it continues to shape over its lifetime. If the seeds of Higgins’s pilot study bear fruit, hair follicle transplantation may grow into a clinically approved treatment for accelerating wound closure, reducing scar formation, and remodelling pre-existing scar tissue.

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