Understanding Topical Growth Factors and Skin Rejuvenation

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There are several different ways growth factors are obtained. The oldest growth factors in the marketplace were obtained from cell fibroblast cultures of newborns’ foreskins. The fibroblasts from fresh circumcision tissue are cultured in a petri dish with media until confluent. The spent media with nutrients depleted and cellular excretion materials are removed, and fresh media is placed in the petri dish. The spent media is known as conditioned media and contains growth factors, cytokines, and soluble proteins. The exact constituents and amounts are not precisely known and may vary from batch to batch based on variables such as how many days elapsed between media replacement, the temperature of the incubator, the confluency of the cells prior to replating, etc. Another source of growth factors is from fibroblasts taken from first-trimester human fetuses.

Current Source of Growth Factors

The newest source of growth factors is from donor tissue. A 3- to 4-mm punch biopsy is taken from the patient and frozen for shipment to a biobank. The fibroblasts are cultured and the spent media is removed. The spent media contain autologous growth factors that are then put into a suitable vehicle. The extra tissue is frozen at –80 °C for later use and provides an additional supply of fibroblasts for renewal of the cell culture. Autologous growth factors can also be obtained by drawing 40 to 60 cc of the patient’s blood and double spinning the blood to obtain platelet-rich plasma (PRP). The autologous growth factors in the PRP include platelet-derived growth factor, epidermal growth factor, and vascular endothelial growth factor. The thinking is that autologous growth factors might be more biologically active because they are specific to the receptors of the donor.

Determining Whether Growth Factors Work

Topical growth factors are very large hydrophilic molecules (larger than 15,000 Da). Molecules that are larger than 500 Da do not penetrate the skin barrier. This is a protective mechanism: Proteins are highly allergenic substances that must be prevented from entering the body. Because of their large size, it can be challenging to achieve penetration of the growth factors. This has led to the use of growth factors before and/or after microneedling. The needle punctures of the skin may enhance penetration and achieve optimized results.

Penetration-Enhanced Growth Factors

Some growth factor serum manufacturers have begun placing the growth factors in liposomes. For example, one company places tumor growth factor (TGF-β) in the center of the hydrophilic liposome surrounded by a protective lipid bilayer. The liposome facilitates passage of the growth factor between the corneocytes, through the intercellular lipids, and in contact with the viable epidermis and dermis, where it may be physiologically active.

Safety of Growth Factors

Concern has been expressed regarding the ability of growth factors to promote the growth of premalignant and malignant cells. Most growth factor products are used by patients with actinically damaged skin, so it is possible that the growth of early actinic keratoses and squamous cell carcinomas could be promoted. If this were the case, however, one might expect to see an increase in these lesions as millions of units of growth factor–containing cosmeceuticals have been sold. Nevertheless, this safety issue cannot be ignored.

Studies to Show Improved Skin Appearance

It can be challenging to separate the effect of the moisturizing vehicle from the effect of the growth factor. You might argue that you cannot separate the effect of the moisturizing vehicle from the growth factor as the cosmeceutical is advertised and sold based on the entire final formulation. A lot of formulation effort goes into formulating the vehicle, which can provide many skin benefits. For example, the vehicle may contain occlusive moisturizers to decrease transepidermal water loss, and humectants to attract and hold water in the skin. These ingredients improve the fine lines caused by facial dehydration. The vehicle may also contain emollient substances to physically smooth the skin surface and soften the skin. Finally, the vehicle may contain light reflective materials that improve facial shine, radiance, and luminosity through purely optical effects. Now you add the growth factor.

Growth factors have been purported to accomplish all of these benefits, from improving the skin barrier to enhancing moisturization to increasing skin softness to smoothing the skin surface. Most of these studies present dermatologist expert grader data as evidence the growth factor cosmeceutical worked. How can the expert grader differentiate between the vehicle-attributed effects and the growth factor–attributed effects? Unfortunately, the expert grader cannot differentiate. Herein lies the challenge in assessing cosmeceutical ingredient efficacy.

Zoe Diana Draelos, MD

Zoe Diana Draelos, MD, is a consulting professor of dermatology at Duke University School of Medicine in Durham, North Carolina, and editor in chief of Dermatology Times.