Category Archives: Skin Regeneration

Scarless Skin Regeneration via Botox-like Nerve Blocking

Skin Regeneration via Nerve Blocking.
Skin regeneration via nerve blocking (aka reducing hyperinnervation).

The relation between skin regeneration and body hair regeneration is very closely connected. I previously discussed it in detail in my post on skin regeneration, wound healing and hair growth. If you want to regenerate damaged human skin, you also need to regenerate skin appendages such as hair follicles, sweat glands, pigment cells, fat cells, sebaceous glands and more.

Full Skin Regeneration by Unblocking Nerves

An interesting new study from Harvard scientists has found that it may be possible to fully regenerate skin without any scars (not the current norm). And the process of doing this might be just a simple Botox-like nerve blocking.

The scientists found that when embryonic mice skin was intentionally damaged three days before birth, the skin regenerated diverse cell types and closely resembled unwounded skin. However, when postnatal mice skin was wounded at five days after birth, the site was “covered by epithelial cells and became packed with collagen scar tissue and abnormally dense nerve fibers and immune cells”.

The densely packed nerves (“hyperinnervation”) are caused by fibroblasts in postnatal wounds upregulating the gene Cxcl12. It recruits excessive nerves to the injured area and impairs the regrowth of other skin-cell types. Basically, nerves are blocking your skin from healing like an embryo.

When the Harvard researchers depleted Cxcl12 in wounds in postnatal mice, this “hyperinnervation” was curtailed. Subsequently, the healing skin regrew diverse cell types. Of most interest, blocking the local nerve signaling with botulinum toxin A (Botox) produced similar effects. According to senior author Ya-Chieh Hsu, professor of stem cell and regenerative biology at the Harvard Stem Cell Institute:

“Before the study, I expected that the key to wound healing would be recreating a series of regeneration-promoting factors to mimic embryonic healing. The solution turned out to be much simpler. I didn’t think that we’d have to retract a brake, which actually is good news — it’s a lot easier. It gives me hope that this might be applicable to improving wound healing in humans.”

The potential for full skin regeneration has positive implications towards full hair regeneration (both body hair and head hair). Perhaps the concept of intentional scalp wounding to regenerate scalp hair may currently be ineffective for many people due to “hyperinnervation”?

Intentional Wounding to Regenerate Hair

Intentional scalp injury when done correctly via microneedling can theoretically also regrow head hair as a side effect of wound healing. However, anecdotal online forums reported results have been mixed and very inconsistent.

But the fact that a 2018 medical case report mentioned how an 80-year old man grew a new pigmented hair after wound healing is very encouraging. As is the famous case of a 78-year old man who grew new hair after accidentally burning his frontal scalp bald region. Also of note, the stimulation of hair growth during wound healing is a phenomenon that was already noted in the 1950s.

The following quote from Dr. George Cotsarelis from the old Follica website is also very encouraging:

“Following skin disruption, cells that migrate to help healing are forced to make a decision: Should I make epidermis, or should I make a hair? There is a window of opportunity in which we can potentially push them to choose the latter, and we believe there are multiple biological pathways to target to enhance this outcome. This regenerative effect is called hair follicle neogenesis.”

Prior to its hibernation, Follica said that its technology is based on the creation of an “embryonic window” in adult skin, allowing new follicles and new hair to form from epithelial stem cells.

Make sure to read my post from last year regarding skin injury, adipocyte lipolysis and subsequent hair growth. Intentional skin wounding is also thought to lead to hair growth via an increase in various fibroblast growth factors and interleukin-1 (IL-1).

Skin Regeneration, Wound Healing and Hair Growth

A lot of hair loss researchers are also heavily involved in skin regeneration and wound healing related work. All three are closely interconnected. If you want to regenerate damaged human skin, you also need to regenerate skin appendages such as hair follicles, sweat glands and sebaceous glands. I originally wrote this post in 2020, and have since added some newer updates at the bottom.

October 24, 2020

Wound Healing and Hair Follicle Growth

Two recent papers published important new findings in regards to wound healing and skin regeneration. I discuss these further below.

Wound healing via skin regeneration is often accompanied by hair follicle regeneration. Or even by brand new hair follicle neogenesis (e.g., Follica). Note that this hair growth after wounding phenomenon was even being researched in the 1950s and 1960s.

Thousands of hair loss sufferers around the world are trying out at-home microneedling and dermarolling. Many of them have seen significant success, although one has to be careful with this type of scalp self-injury.

Human embryonic and neonatal skin has the potential to regenerate after wounding. This includes fully functioning hair follicles. However, adult skin no longer has such regenerative capabilities. Researchers have been trying for years to find ways to coax salamander-like regenerative powers in humans. If not for whole limbs, at least for hair growing skin to cover baldness for our sake.

New Studies on Wound Healing and Skin Regeneration with Hair Follicles

1) In September 2020, a team that included Dr. Jeff Biernaskie published a study on the regenerative potential of dermal fibroblasts during wound healing. They identified a specific population of progenitor cells that reside within the dermis and which aid in wound healing. I covered Dr. Biernaskie and his University of Calgary team in detail in 2020.

Skin Regeneration Regulators
Skin Regeneration Regulators. Source: Bernaskie Lab GitHub.

This latest research is shared on GitHub. Also see Biernaskie Lab. According to the findings, Runx1, retinoic acid, and Hic1 control mesenchymal regenerative capabilities.

According to this summary, Dr. Biernaskie said that they have shown the following:

“You can alter the wound environment with drugs, or modify the genetics of these progenitor cells directly. Both are sufficient to change their behavior during wound healing. And that can have really quite impressive effects on healing that includes regeneration of new hair follicles, glands and fat within the wounded skin.” 

“It suggests that the adult wound-responsive cells do in fact harbor a latent regenerative capacity, it just simply needs to be unmasked.”

2) Also in September 2020, a new study from the University of Washington identified Wnt transcription factor Lymphoid enhancer-binding factor 1 (LEF1) as the key factor in adult skin regeneration.

LEF1 gene expression in fibroblasts has the potential in adult skin to repair itself like the skin of a newborn baby. This skin can also grow new hair follicles.

In an interview with lead author Dr. Ryan Driskell (link no longer working), he said the following:

“We identified a genetic factor that allows adult skin to repair itself like the skin of a newborn baby.”

Skinregeneration.org

The authors of the above study have started a new site called skinregeneration.org. The site’s mission is to provide a platform for scientists to easily query large datasets that focus on skin wounding and scarring repair.

For further information, see the Driskell Laboratory site at Washington State University.

Update: July 8, 2022 — A WSU research team led by Dr. Ryan Driskell is researching how to regenerate skin without scarring. This would be done by reactivating Lef1 expression in adult fibroblasts. In effect, this would turn adult skin into more youthful young skin.

Hair, Skin and Wounds all Interconnected

While researching for this post, I could not believe the number of diverse past posts that I have written on this blog that have focused on skin regeneration, wound healing and hair formation.

Regenerating hair follicle after wounding.
Wound induced single hair follicle neogenesis in a bald old man.
  • Another item of interest entails activation of the Sonic Hedgehog Pathway and subsequent wound healing and hair regrowth.
  • Also see the connection between wounding, interleukin-1 and hair growth.
  • For a fascinating and yet comedic take, I recommend reading “never too old to regenerate hair“.
  • The hype surrounding Follica (US) and wounding induced hair regeneration. And the popular related subjects of microneedling and dermarolling for hair growth, which that I have covered a number of times. Update: Follica went into hibernation in 2023 despite 15 years of research and encouraging statements regarding the hair growth potential of intentional scalp injury.

Renowned hair loss researchers such as Dr. George Cotsarelis, Dr. Luis Garza, Dr. Elaine Fuchs and Dr. Mayumi Ito have all also conducted frequent research on skin regeneration. I have discussed their work in past posts if you search for their names.

My gut feeling is that whenever there is a fully effective cure for hair loss, there is a strong likelihood that there will also be a cure for quality skin regeneration.

Skin Gun and Spray-On Skin

It seems like the technology to repair skin has improved significantly during the past decade. There is an especially unmet need when it comes to treating skin that has been burnt badly.

One of the technologies that I used to very curious about is the skin gun that was widely hyped in 2011. I have not heard much about this in recent years. RenovaCare acquired the technology in 2013. The company’s skin gun and spray-on stem cells for wound healing are trademarked under the names SkinGun™ and CellMist™.

Update: June 21, 2021

Hair Follicle Mesenchymal Activity During Wounding Healing

I am updating this post because an important new study on wound healing and hair follicle mesenchymal stem cell activity was published in June 2021. The Israeli researchers behind this paper concluded the following:

“During wound healing, dermal papilla (DP) and dermal sheath (DS) cells move towards the wound, but do not directly participate in follicle neogenesis.”

They further elaborate that follicle neogenesis during wound healing is a genuine de-novo process. The new follicle formation does not rely on any preexisting components from preexisting follicles.

Update: February 2022 — Another interesting new study titled “Cellular Memories: More Than Skin Deep.” Co-author is Dr. George Cotsarelis.

Update: March 2023 — In vivo reprogramming of wound-resident cells generates skin with hair.