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A Review on “Skin Boosters”: Hyaluronic Acid, Poly-L-lactic Acid and Pol-D-lactic Acid, Polydeoxyribonucleotide, Polynucleotides, Growth Factor, and Exosome

Abstract

The term “skin booster” was introduced in 2015 to describe the use of “Restylane Vital” and “Vital Light” hyaluronic acid filler products to improve skin aging and reduce wrinkles by supplying hyaluronic acid filler to the dermis. Previously, hyaluronic acid fillers were mainly used to increase skin volume. Skin boosters are a range of ingredients used to improve dermal conditions. Although Restylane Skinboosters such as “Restylane Vital” and “Vital Light” are registered trademarks, the term “skin booster” is now commonly used by the public, just as “Botox” is used for botulinum toxin produced by Allergan. The article discusses representative skin booster ingredients, but there is no clear definition of the term. The authors believe that skin boosters include various ingredients used to improve the extracellular matrix of the dermis to enhance the skin’s condition. It is important to note that products approved as cosmetics in Korea but delivered through injection to the dermal layer or below violate medical law. Therefore, caution should be exercised when selecting products. This article focuses on introducing five main ingredients that have recently become issues: hyaluronic acid, polydeoxyribonucleotide, polynucleotide, oligonucleotide, and amino acids. The article discusses provided unbiased descriptions of their clinical experiences to help readers make informed choices. In the article it is not promoted with specific products for profit, and the product evaluation is based purely on clinical experience. In conclusion, skin boosters are a range of ingredients that improve the dermal condition of the skin, and this article provides information on popular ingredients to help readers choose the right products.

Key words: Skin booster, Hyaluronic acid filler, Botulinum neurotoxin, Poly-L-lactic acid, Pol-D-lactic acid, Polydeoxyribonucleotide, Polynucleotides, Growth factor, Exosome

INTRODUCTION

Botulinum neurotoxin and fillers are the most effective non-surgical, anti-aging treatments for facial restorations. Botulinum neurotoxin is a major treatment for wrinkles and muscle hypertrophy [1-12]. Fillers are used to contour the facial shape and correct sunken areas of the face related to the aging process [13,14]. On the other hand, since 2015, the term “skin booster” has been used in the skincare and cosmetic surgery market, as “Restylane Vital” and “Restylane Vital Light”, which are hyaluronic acid (HA) filler products, were used to supply HA to the dermal layer of the skin to improve skin aging and reduce wrinkles. Although HA fillers were previously used primarily for volume increase, the use of HA fillers for skin booster purposes started with the goal of improving the skin condition by improving the extracellular matrix (ECM) of the dermal layer. Although Restylane Skinboosters “Vital” and “Vital Light” are registered trademarks for skin boosters, the term “skin booster” is currently used by the public as a general noun, just as “Botox” is used as a general noun for products used in botulinum toxin procedures by Allergan.

Although the types and purposes of skin boosters encountered by the aesthetic purposes are currently more diverse than ever, no special definition has been discussed. However, it is reasonable to discuss the definition of skin boosters as a broad range of ingredients, including various ingredients used to improve the condition of the skin. Nevertheless, it should be noted that products that are not pharmaceuticals but have been approved as cosmetics in Korea and are delivered to the dermal layer or below through injections are classified as violations of the medical law. Therefore, special attention is required. In this article, representative skin-booster ingredients are introduced, and although specific product names are mentioned, the study aims to provide unbiased descriptions of their clinical experiences to assist readers in making informed choices. The article has not promoted or introduced specific products for profit, and any evaluation of products is based purely on the clinical experiences. This article focuses on introducing five main ingredients that have recently become an issue.

HYALURONIC ACID FILLER

As mentioned in the introduction section, the most representative HA filler is “Restylane Vital”. Fillers with various properties, such as the size of filler particles, less cross-linking, or improved injection sensation have been produced by many companies and diversely used commercially [15]. HA is present in the dermal layer of the skin and is known for its ability to maintain and absorb moisture, as well as to stimulate and regulate the secretion of growth factors in connective tissues of the skin [16]. Recent studies have suggested that fillers containing various amino acids that help improve the dermal environment or the simultaneous use of picosecond lasers after filler injection can enhance the effect of the dermal environment and the wound healing process. As a result, the authors consider that HA filler products, which are a type of skin booster, will strengthen their market position through continuous changes and improvements. However, the drawbacks of this procedure include the following: first, its longevity, which varies according to the literature but generally lasts for approximately 6 months after three sessions; second, pain is experienced during injections; and third, delivering the HA filler accurately to the desired location is a challenge. The question of whether injections can accurately deliver HA fillers to the dermis has been raised repeatedly; however, as the methods of delivering HA to the dermis become more diverse and accurate, even better results is expected in the future [13].

POLY-L-LACTIC ACID (PLLA) AND POLYMER D-LACTIC ACID (PDLA)

In the rapidly growing Korean cosmetic surgery market, polymers are currently being used as skin boosters. As discussed earlier, HA fillers are good in terms of naturalness and skin-boosting purposes; however, a drawback is their short-term volume retention in the treatment of scars and other issues. Therefore, a skin booster filler that focuses more on volume retention and guarantees safe sustainability is required in clinical settings. Sculptra, which uses PLLA as a replacement material, has been used for this purpose [17]. Sculptra was originally an effective product used to induce large-scale collagen synthesis in patients with a rapid decrease in facial volume, such as patients with acquired immunodeficiency syndrome (AIDS). However, existing concerns include particle irregularities, particle size, unevenness, protrusion, and formation of granulomas. To overcome these challenges, PDLA, an isomer of PLA (Polylactic acid), was produced. Products, such as Juvelook® and Lenisna®, which have made particle sizes more uniform and smaller, are being used. These products contain HA instead of carboxymethylcellulose; however, the use of polymer products inside the dermis still raises vague fears among physicians; therefore, long-term observation is required regarding immune reactions that may involve giant cells on a large scale [15,18]. This is similar to the experience with granulomas when using PLLA in the past.

DEOXYRIBONUCLEIC FRAGMENTS (POLYDEOXYRIBONUCLEOTIDE, PDRN; POLYNUCLEOTIDES, PN)

These substances are more widely used in the Korean beauty and skin care markets than procedures using fillers represented by HA. This is because, apart from concerns regarding efficacy, problems such as lumps, which are associated with HA fillers, are rarely encounter. In the process of wound healing, especially in the early stages when the salvage pathway needs to be stimulated, the human body uses deoxyribonucleic acid (DNA) fragments found in the vicinity of the wound as ingredients for wound healing. Recent reports indicate that DNA fragments have been used in various cosmetic procedures. Before wound healing, the actual promotion of vascular endothelial growth factor (VEGF) is known to regulate angiogenesis. Various products are available, and it is known that the rejuvenation effect is better when HA is included and the size of DNA fragments is large. DNA fragments are also widely used in the treatment of hair loss, and experiments comparing them with PRP in skin rejuvenation procedures have shown similar results.

GROWTH FACTORS

Historically, growth factors are the oldest type of skin booster. Growth factors are known to stimulate various cells to aid in wound healing. They are not only injected into the skin via methods, such as PRP, but are also increasingly included in cosmetics as an ingredient for skin boosting [19]. Moreover, almost all products contain substances that either include growth factors or promote their production [20]. However, most cell receptors that accept growth factors are from the damaged cells rather in normal cells [21]. We need to consider whether supplying growth factors to normal skin has any benefits. The authors suppose that growth factor therapy is more effective in inducing wound healing processes when stimulations, such as with energy-based devices (EBD) or needling, are present. Second, it takes time for various growth factor receptors to be fully formed at the beginning of the wound-healing process. Typically, according to the literature, except for PDGF, it takes approximately 12-24 hours for receptors to be fully formed [22]. Therefore, it is necessary to consider whether it is helpful to use growth factors in an unsafe situation for receptors [23]. However, The authors assume that substances that promote salvage pathways, such as PDRN and PN, would be more helpful in the early stages of wound healing. Third, most growth factors have an overall positive charge. This is the biggest disadvantage in the skin penetration stage; however, after penetrating the dermis, cells have a negative charge and are known to be attract these factors. It is worth noting that the epidermis in wounds has a negative charge, making it easier for growth factors to penetrate. In addition, it is not good to rely solely on normal skin absorption of growth factors without using various absorption-promoting methods. Recently, various growth factors have been used for skin pigment therapy. Among them, endothelial growth fact (EGF) is known to suppress melanogenesis and decrease tyrosinase activity, making it a good option for post-laser pigmentation. Furthermore, differentiating between the use of various growth factors is essential.

EXOSOME

Exosomes are one of the most prominent skin boosters. Exosomes are known as Extracellular Vehicles that are produced inside or outside the cell membrane, and are known to transfer information, such as micro-endothelial growth fact (miRNA)s and peptides between cells [24]. They are mainly used in the clinical settings for facial rejuvenation and scalp treatment. Unlike growth factors, exosomes are generally negatively charged, making them more easily deliverable through the skin. There are three main methods for mass-producing and obtaining exosomes, namely, centrifugation, vertical diffusion, and stem cell stimulation. However, the production efficiency of exosomes is not yet optimal, which leads to increased production costs. Another issue is that it is difficult to identify the specific information contained within exosomes. For example, if there is a miRNA that is good for treating age spots, it is difficult to separate and extract only that information. This makes it difficult to predict and perform procedures based on specific results when injecting exosomes. Additionally, exosomes vary in size, making it challenging to filter and refine them. Therefore, exosomes are currently very expensive, and the development of exosomes for multiple purposes and mass production is thought to be the future of exosomes as skin boosters. It should be noted that exosome cosmetic products currently available in Korea are mostly composed of small quantities of exosomes and a significant amount of growth factors and hyaluronic acid. In the future, we hope to develop more economically efficient products with higher concentrations of exosomes.

DISCUSSION

Various ingredients, such as stem cells, stem cell culture medium, and amino acids, are currently being used as skin boosters. However, owing to space constraints, we did not include these details in this article.

The crucial aspect of enhancing the effectiveness of skin boosters is the delivery of the ingredients through the skin barrier, which is responsible for protecting the body. It is essential to find a way to pass through the skin without causing pain and to deliver the ingredients to the dermis.

Various methods can be employed to achieve this, including injection into the lesion (also known as mesotherapy), iontophoresis, electrophoresis, microneedling, high-frequency needling, ultrasound, laser, plasma, and transcutaneous drug delivery using a needless injector. The method of delivery is as important as the type of skin booster chosen [9,25].

For example, while subcutaneous injection of PDLA, known as a polymer, is possible through needle injection, in the era of microinvasive needling with radiofrequency, it is now possible to inject subcutaneously through appropriate hydration and machine-based management, such as ultrasound.

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