Collagen - Bernstein Medical - Center for Hair Restoration
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by Jeff Teumer, PhD
Hair Transplant International Forum, Volume 18, Number 3, May/June 2008

Follicular cell implantation (FCI) is based on the ability of the dermal papilla (DP) cells, found at the bottom of hair follicles, to stimulate new hairs to form. DP cells can be grown and multiplied in a culture so that a very small number of cells can produce enough follicles to cover an entire bald scalp.

In order to produce new follicles, two types of cells must be present. The first is Keratinocytes, the major cell type in the hair follicle, and the second are dermal papillae cells (DP) which lie in the upper part of the dermis, just below the hair follicle. It appears that the DP cells can induce the overlying keratinocytes to form hair follicles. There are a number of proposed techniques for hair regeneration that use combinations of cells that are implanted in the skin. The two major techniques involve either transplanting dermal papillae cells by themselves into the skin or implanting them with keratinocytes. These techniques can be used with or without an associated matrix used to help orient the newly forming follicles.

Implanting Dermal Papillae Cells Alone

  1. Implanting DP cells by themselves into the dermis, with the hope that they will cause the overlying skin cells (keratinocytes) to be transformed from normal skin cells into hair follicles. This method is called “follicular neo-genesis” since new hair is formed where none previously existed.
  2. Cells of the dermal papillae are placed alongside miniaturized follicles. The transplanted cells would induce the keratinocytes of the miniaturized follicles to grow into a terminal hair. A potential advantage of this technique is that the existing miniaturized follicles already have the proper structure and orientation to produce a natural look growth.

Implanting Dermal Papillae with Keratinocytes

  1. A mixed suspension of cultured keratinocytes and DP cells are implanted into the skin.
  2. Keratinocytes and DP cells are cultured together such that full or partial hair formation takes place in a culture dish. These culture-grown hairs, or “proto-hairs,” are then implanted into the patient. The advantage of using a proto-hair is that there would be better control over the direction of hair growth because of the structural orientation of the proto-hair.

Cell Implantation using a Matrix

  1. A variation of the above techniques is to use a matrix to help orient the implanted cells. This could be either an artificial matrix composed of materials such Dacron or it could be a biological matrix composed of collagen or other tissue components. The matrix would act like a scaffold to help cells organize to form a follicle. If the matrix were filamentous (like a hair) it could help direct the growth of the growing follicle. A matrix could be used with dermal papillae cells alone or in combination with cultured keratinocytes.

With all of the varied approaches for FCI, the aim is to combine keratinocytes and DP cells to efficiently and reproducibly generate thousands of follicles for hair restoration. In some cases, cells are combined in vivo and all of the hair formation must take place in the body after implantation, while in others, some hair formation takes place in culture before implantation.

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Q: It is my understanding that as a person loses his or her hair, the skin of the scalp undergoes a number of changes, namely there is a loss of fat, an increase in cellular atrophy, and of course the dreaded perifollicular fibrosis (now that’s a mouthful). It seems to me that these changes, in particular the fibrotic scarring, are the main obstacles in the way of regrowth, and the reason Propecia does not work for extensively bald men. What can be done about this demon we call fibrosis? Can it be slowed, stopped, prevented, reversed? If we could somehow counteract collagen formation, wouldn’t our baldness problems be solved for good? If a bald scalp is atrophic, how does it have the capacity to hold a whole new head of transplanted hair? Is there a limitation to the number of hairs we can transplant (outside of donor limitations)? — R.L., Rivington, C.T.

A: The findings that you are describing are well documented; however, it is not clear if these changes are the cause of the hair loss or are the result of having lost one’s hair. Most likely, the DHT causes the hair follicles to miniaturize and eventually disappear. This, in turn, causes the scalp to thin and lose its abundant blood supply (whose purpose is to nourish the follicles). The changes in the scalp are also affected by normal aging, which causes alterations in connective tissue including the breakdown of collagen and other components of the skin. The changes seen with aging are greatly accelerated by chronic sun exposure.

Fortunately, even with long-standing baldness there is still enough blood supply to support a hair transplant, although there are some limitations. One should perform a hair transplant with a lower density of grafts when patients have thin, bald fibrotic scalps since the blood supply is diminished.

The most important factor, however, is photo change. The sun dramatically alters the connective tissue making the grafts less secure in their sites and alters the vasculature, (blood vessels) decreasing tissue perfusion (blood flow to the tissues). When there is bald atrophic, sun damaged scalp, I generally perform two hair transplant sessions of lower density (in place of one) spaced at least a year apart to give time for the scalp to heal and blood flow to increase in the area.

I often have the patient treated with topical 5-flurouracil before the surgery to improve the quality of the skin and to treat or prevent pre-cancerous growths from the sun.

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Q: Why can donor hair become frizzy and dry once transplanted? — G.F., Stamford, C.T.

A: Frizzing and kinkiness is a temporary phenomenon that is part of the normal healing process after a follicular unit hair transplant. During the healing process, the new collagen that forms around the grafts can alter their growth. Over time, usually within a year, this collagen matures and the hair quality usually returns to normal. If grafts have been excessively traumatized or grafts larger than follicular units have been used, these changes are more likely to be permanent.

Dry hair is felt to be caused in part by trimming follicular units too closely and thus removing the sebaceous glands which normally provide an oily film to the surface of the hair and skin. With grafts smaller than follicular units (i.e. with closely trimmed micro-grafts) the risk is even greater.

To prevent this, in the dissection phase of the hair transplant, one should isolate intact follicular units from the donor tissue and trim away excess skin, but not trim the follicular units “to the quick.” Excess trimming, besides removing the sebaceous glands, also makes the grafts more subject to drying, warming and mechanical trauma (particularly during graft placing).

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Cosmetic Surgery Times features Dr. Bernstein’s presentation to the 55th annual meeting of the American Academy of Dermatology in their April 1997 issue.

The article entitled, “Follicular Transplants Mimic Natural Hair Growth Patterns,” describes Dr. Bernstein’s introduction of his new procedure, Follicular Unit Transplantation, to the academy as well as the keys to making the technique successful. Find the complete article below:

Form Follows Function: Follicular Transplants Mimic Natural Hair Growth Patterns

By Neil Osterweil
Contributing Editor

SAN FRANCISCO – In recent years, many hair replacement surgeons have adopted the modem architecture philosophy that “less is more,” moving from the use of hair plugs, to split grafts, to minigrafts and, finally, micrografts. But at least one hair transplant specialist contends that a more appropriate architectural dictum is “form follows function.”

In other words, the surgeon should let the technique fit the head, and not the other way around, suggested Robert M. Bernstein, MD, at the 55th annual meeting of the American Academy of Dermatology.

Dr. Bernstein is an assistant clinical professor of dermatology at the College of Physicians and Surgeons, Columbia University in New York. He described his “follicular transplantation” technique in a meeting presentation and in an interview with COSMETIC SURGERY TIMES.

Natural Hair Groups Used

Dr. Robert M. Bernstein“Hair doesn’t grow singly it grows in naturally occurring groups of from one to four hairs. In follicular transplantation, we use these naturally occurring groups as the unit of the transplant,” he told CST.

The typical follicular unit consists of one to four terminal hairs, one or two vellus hairs, sebaceous glands, subcutaneous fat and a band of collagen which circumscribes and defines the unit. In the follicular transplant technique, the follicular unit is carefully dissected and removed, and then the intervening skin is discarded. This enables the donor site to be small, allowing implantation through a small needle poke. Because trauma to the recipient sites is minimal, the entire procedure can be performed at one time. Dr. Bernstein and colleagues have implanted as many as 3,900 follicular units in a single, 1 day session.

Keys to the follicular transplant technique are:

Identify the patient’s natural hair groupings and isolate the individual follicular units – Hair groupings are assessed with an instrument called a densitometer, and the average size of a person’s groups can be easily calculated. This information is critical in the planning of the transplant. The density of hairs in an individual measured as the number of hairs per square millimeter of skin is quite variable, but the density of follicular units is relatively constant within individual races.

Most people of Caucasian ancestry have a density of approximately one group per millimeter; people of Asian and African descent tend to have slightly less dense growth patterns, although the characteristics of the person’s hair (such as wavy or wiry hair), can give a full appearance even with low density.

If a patient has an average hair density of two, he will receive mostly two hair implants, with some one-hair and three hair implants mixed in. “If you try to make the groups larger than they occur naturally, they will look pluggy. If you try to make them smaller than they naturally occur, they’re not going to grow as well, because each group is actually a little biologic machine that makes the hair — it’s an anatomic unit. If you break it up it just doesn’t grow as well,” Dr. Bernstein observed.

Form Follows Function: Follicular Transplants Mimic Natural Hair Growth Patterns
A 38-year old man with a Norwood Class 5A/6 hair loss pattern undergoes a single procedure of 2,500 follicular implants. The result 11 months later. (Photos courtesy of Robert M. Bernstein, MD)

Harvest meticulously – The acquisition and preparation of grafts must be carefully performed to ensure success for this demanding technique. Highly trained, skilled assistants are essential to the success of the procedure. Dr. Bernstein noted that he uses a highly trained team of up to 10 assistants to produce the implants for a single case. “The assistants, who range from medical technicians to registered nurses, are such an integral part of the procedure that they must become expert in their specific tasks for the surgery to be successful.” The physician must be able to skillfully harvest the donor strip and must be able to make accurate judgments about the size of grafts intra-operatively and adjust the technique accordingly. Dissection and placing of the follicular units is the most labor intensive part of the procedure.

Design the recipient area well – The recipient sites are carefully distributed so that a natural looking pattern is maintained throughout the recipient area. An important consideration for this stage of the procedure is to “frame the face and spare the crown” so those facial features are kept in correct proportion. A common mistake in hair replacement, said Dr. Bernstein, is to create a hairline that is too high thereby elongating the forehead and accentuating, rather than minimizing, the patient’s baldness. It is also important to avoid or eliminate contrast between the implants and surrounding skin by creating a soft transition zone of single hairs and to have the hair emerge from the scalp at natural angles.

Procedure Lowers Cost

Although the procedure is highly labor intensive, it can actually be less expensive than conventional hair replacement surgery, because it can be performed in a single, but lengthy, session.

“It is also much more efficient and conserves donor hair much better than conventional hair transplants. Every time you make an incision in the person’s scalp you waste some hair and make the remaining hair more difficult to remove. Accessing the donor area just once or twice will increase the total amount of hair that is available for the transplant,” Dr. Bernstein told CST.

“In the very near future, the procedure will be improved and made more affordable with automated instruments that will enable the surgeon to make sites and implant the hair in a single motion. This will also decrease the possibility of injury to the implants by reducing handling and keeping the grafts uniformly cool and moist. It is possible that someday hair follicles may be cloned to provide a virtually unlimited supply of custom follicular units, but until then the finite nature of a person’s donor supply must be respected,” concluded the doctor.

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