Topical growth factor preparations for facial skin rejuvenation: A systematic review

Background

Cosmeceutical preparations containing growth factors (GFs) are widely used for facial rejuvenation.

Objective

We performed a systematic review to assess the evidence regarding their safety and effectiveness for facial rejuvenation.

Methods

Electronic databases (Cochrane Library, EMBASE, MEDLINE, and Scopus) were searched from 2000 to October 2022 for prospective trials and case series assessing topical GF preparations for facial rejuvenation in 10 or more participants.

Results

Thirty-three studies, including 9 randomized controlled trials (RCTs) and 24 uncontrolled case series, representing 1180 participants receiving 23 different topical preparations containing GFs met the inclusion criteria and were included. Of the 33 studies, nine used a placebo or active control. The GF preparations were applied twice daily in all except two studies, with a mean treatment duration of 3 months. Based on the investigator's assessment, preparations containing GFs induce a modest improvement in skin texture (median < 50%), fine lines/wrinkles (median < 35%), and overall facial appearance (median < 20%) versus baseline. Participant-assessed improvement was generally higher than investigator-assessed response. Three comparative RCTs showed no statistically significant differences between treatments. Studies were limited by heterogeneity with regard to the source and number of GFs used in the preparations, information about additional ingredients, and lack of standardization in the outcome measures. The preparations were associated with a low risk of adverse events. The persistence of the clinical improvements beyond 6 months is not known.

Conclusions

Administration of topical preparations containing GFs appears to be effective for facial skin rejuvenation, as demonstrated by the investigator- and participant-reported outcome measures.     

The lamellar peel: A sequential nonablative and ablative laser treatment for facial skin rejuvenation

Objectives. Ablative and nonablative laser treatments have established themselves independently in the rejuvenation of aging skin. This study was designed to determine the effects of sequential nonablative and ablative laser treatments on facial skin.

Materials and methods. Twelve patients, ages 32–56 years, with skin phototypes I‐IV, received three treatments spaced six weeks apart. Each treatment consisted of one pass with 1319‐nm Nd:YAG laser at 16 J/cm², 50 ms pulse duration. This was immediately followed by one pass of 2940‐nm Er:YAG laser at 5 J/cm². Photographs and biopsies were taken prior to the first treatment and following the third treatment.

Results. Clinical improvements in facial skin tone and texture, acne scarring and dyschromia were noted in all patients. Histologic changes included a more compact epidermal granular layer and lamellar collagen formation with decreased solar elastosis in the dermis. Compared to controls, treated skin had a thicker, more homogeneous papillary dermis.

Conclusion. The sequential use of nonablative and superficial ablative laser treatments clinically and histologically improved photodamaged and chronologically aged skin. This occurred with minimal recovery and little morbidity, demonstrating this laser application to be a safe and effective method for facial rejuvenation.     

Histological evidence for skin rejuvenation using a combination of pneumatic energy,broadband light,and growth factor therapy

Abstract

Background and objective: A variety of laser or light-based devices have been developed for skin rejuvenation. This study evaluates the efficacy (at the microscopic level) of a combination of pneumatic energy, broadband light, and profusion tip-delivered epidermal growth factor (EGF). Methods: Healthy adult Japanese volunteers were recruited for this study. The posterior parts of the left and right arms were treated with a device that combines pneumatic energy and broadband light (Isolaz device). The left arms were also treated with EGF through a tip. Each subject received four treatments at 10-day intervals. Biopsy specimens obtained 3 weeks after the second treatment and 3 weeks after the fourth treatment were examined for histological study. Results: After two treatments, elastin fibers and fibroblasts in the dermal papillary layers of the left arms were increased compared to the right arms. A mean of 173.9 cells positive for proliferating cell nuclear antibody (PCNA) were observed on the left arm compared to 101.0 on the right arm. After the fourth treatment, angiogenesis and increased collagen fibers were observed in the dermal papillary layers of both arms. Conclusion: Four treatments with the addition of the profusion tip appear to hasten new collagen and elastin fiber formation, and the increase of PCNA positive cells so that dermal remodeling begins at an earlier stage than with the Isolaz alone.     

Long‐chain polynucleotide filler for skin rejuvenation: efficacy and complications in five patients

Aging well has become the new target of preventative medicine, and aesthetic dermatology can contribute to this request. The polynucleotide (PN) containing products not only fill the space, but improve tissue regeneration, resulting in more natural tissue regeneration. Five Korean women received four times injections of long‐chain PN filler in two‐week intervals for skin rejuvenation. About 0.05 mL of material was injected in 40 points of one‐side cheek. The pore and skin thickness were markedly improved in the patients in their 30s, whereas skin tone, melanin, wrinkles, and sagging were noticeably improved for patients in their 40s. There are no serious side effects. In conclusion, intradermal long‐chain PN filler injection seems to be an effective and safe treatment for skin rejuvenation.     

Comparison of the effects of carboxytherapy and radiofrequency on skin rejuvenation

Background: Carboxytherapy (CA) refers to the cutaneous and subcutaneous administration of CO₂ for therapeutic purposes. Radiofrequency (RF) is a method that uses electric current for heating layers of the skin. Both techniques are indicated for the treatment of skin laxity. Objective: The aim of this study was to compare the effects of CA and RF on human skin. Methods: After eight patients underwent abdominoplasty, each of them received a single treatment of CA and a single treatment of RF on the right and left infra-umbilical regions, respectively. In the infra-umbilical region, CA was performed on the right and RF was performed on the left side. Untreated skin was used as a control. The sample collection period lasted 120 days. CA was administered at a velocity of 40 mL/min, and the total quantity of CO₂ infused was approximately 20 mL. RF was carried out at a temperature higher than 40°C on the epidermis for 5 min. Results: CA and RF led to collagen remodeling; however, this result was more evident and lasted longer with RF. With CA an increase in elastic fibers was observed, whereas with RF no alteration was observed. Conclusion: Our results suggest that RF is more efficient than CA in stimulating collagen synthesis.     

Bioactive reagents used in mesotherapy for skin rejuvenation in vivo induce diverse physiological processes in human skin fibroblasts in vitro- a pilot study

Abstract: The promise of mesotherapy is maintenance and/or recovery of a youthful skin with a firm, bright and moisturized texture. Currently applied medications employ microinjections of hyaluronic acid, vitamins, minerals and amino acids into the superficial layer of the skin. However, the molecular and cellular processes underlying mesotherapy are still elusive. Here we analysed the effect of five distinct medication formulas on pivotal parameters involved in skin ageing, that is collagen expression, cell proliferation and morphological changes using normal human skin fibroblast cultures in vitro. Whereas in the presence of hyaluronic acid, NCTF135^® and NCTF135HA^®, cell proliferation was comparable to control cultures; however, with higher expression of collagen type‐1, matrix metalloproteinase‐1 and tissue inhibitor of matrix metalloproteinase‐1, addition of Soluvit^® N and Meso‐BK led to apoptosis and/or necrosis of human fibroblasts. The data indicate that bioactive reagents currently applied for skin rejuvenation elicit strikingly divergent physiological processes in human skin fibroblast in vitro.     

A retrospective study on the clinical efficacy of the intense pulsed light source for photodamage and skin rejuvenation

Objective: The objective of this retrospective review is to investigate the long-term effect of skin rejuvenation by the intense pulsed light (IPL) source for the treatment of photoaging. Methods: From 5300 clinical cases that our department has treated with the IPL, the first 2534 were chosen for this study. Each patient received a minimum of 3 IPL treatments during this time—many were yearly treatments. Clinical photographs were taken on a yearly basis for up to 12 years and sent to a blinded independent panel to study the effects of continuous IPL treatments. Results: Results showed that the effective rate for the IPL was between 88.24% and 96.45%. Conclusions: IPL therapy is an effective treatment for photoaging and can truly have an effect on reversing the signs of photodamage on skin.     

Effects of the Nd:YAG 1320-nm laser on skin rejuvenation: Clinical and histological correlations

Abstract

The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser is a popular non-ablative treatment used for skin rejuvenation. The purpose of this prospective study was to evaluate the clinical effects, coupled with a quantitative assessment, of the histological changes in response to Nd:YAG 1320-nm laser treatment of periocular wrinkles. Six volunteers with Fitzpatrick skin types III and IV and Glogau class I–II wrinkles were subjected to 3 months of Nd:YAG 1320-nm treatment in the periocular area (six sessions at 2-week intervals). Volunteers were photographed, and skin biopsies were obtained at baseline as well as 3 and 6 months after the start of treatments. Quantitative evaluation of total elastin, newly synthesized tropoelastin, collagen types I, III and VII, and newly synthesized collagen was performed using a computerized morphometric analysis. A noticeable clinical and histological improvement was observed after Nd:YAG 1320-nm treatment. Collagen types I, III and VII, as well as newly synthesized collagen, together with tropoelastin showed a statistically significant increase in response to treatment, while the mean level of total elastin was significantly decreased after treatment. Our data suggest that Nd:YAG 1320 nm is an effective treatment for skin rejuvenation as it stimulates the repair processes, and reverses the clinical, as well as the histopathological, signs of skin aging.     

Clinical and histologic findings after use of a novel combined retinol,tripeptide, and glaucine containing cream in the treatment of photo-aged skin

Background

Neck skin is thinner and has a more delicate dermal layer than facial skin. The studied product was specifically formulated for the neck combining a hydrating delivery system with a trifunctional corrective technology composed of 0.2% pure retinol, 2.5% tripeptide concentrate, and 5.0% glaucine complex to help improvement in signs of aging.

Objectives

To evaluate cosmetic and histologic changes 3 months after treatment using immunostains for Type I collagen, Type III collagen, and glycosaminoglycan (GAGS). In addition, overall clinical improvement in photoaged skin was measured by both Griffith's photonumeric photoaging scale, photographic improvement, and questionnaires.

Methods

This study was an open-label, blinded clinical trial evaluating a combined retinol, tripeptide, and glaucine containing cream in the treatment of photo-aged skin. The study enrolled a total of 20 healthy male or female subjects, who applied the product for 3 months to their face and neck.

Results

Clinical as well histologic changes were consistent with improvement in all 20 subjects.

Conclusion

Use of a combined retinol, tripeptide, and glaucine containing cream led to both clinical and histologic improvement of phototoaging.     

Neck skin rejuvenation: Histological and clinical changes after combined therapy with a fractional non-ablative laser and stabilized hyaluronic acid-based gel of non-animal origin

Abstract

Background: The laser Affirm? (LA) is a microthermal, non-ablative fractional laser used for skin rejuvenation. Restylane Vital? Light (RVL) in the Restylane^® Injector, a formulation of stabilized hyaluronic acid-based gel of non-animal origin, is indicated for rejuvenation of delicate skin. Objectives: To assess the interaction between the LA and RVL in aging skin of the neck using clinical and histological parameters, and to determine whether combined therapy is effective. Methods: Nine female patients aged 42–62 years received four treatments, each comprising RVL followed immediately by LA treatment. Photographs and skin biopsies were taken before treatment, after the fourth session and 1 month later. Results: Improvements in fine wrinkles, tightness and skin texture were observed. Histologic evaluations showed favourable changes in cellularity, collagen and elastic fibres. Laser-induced effects (400 μm) and an inflammatory reaction (1000 μm) were seen. RVL was present at the mid–deep dermis (1000–1500 μm). Conclusions: Combined treatment with the LA and RVL improved skin appearance and structure as assessed, for the first time, with histology. The LA produced epidermal and superficial dermal changes whereas RVL acted deeper, together treating the full skin thickness.     

The comparison of skin rejuvenation effects of vitamin A,fractional laser,and their combination on rat

Background: Because of long-term exposure of skin, skin aging is an unavoidable natural law with age. Traditional Vitamin A and novel ablative fractional laser technique both have the effects of skin rejuvenation, and studies have demonstrated both of them have apparent clinical efficacy and histology-improving effects on photo-aging skin. Materials and methods: 45 female healthy Wistar rats were selected and the depilation areas of every rat were divided into four regions: control region(Region A), Vitamin A acid region(Region B), combination treatment region(Region C), and fractional laser region(Region D). 0.025% Vitamin A acid cream was applied to Region B and C every day for 3 weeks; Region C and D were irradiated once with 10600nm CO₂ fractional laser on the first day of the trail. The skin tissue was dissected and placed into liquid nitrogen according to the design. The real-time quantitative PCR and western blotting methods were taken to detect the expression changes of miR-29a, Akt, TGF-β, and mRNA of type III pre-collagen. Results: It can be seen from the results of the real-time quantitative PCR that the mRNA expression levels of type III pre-collagen, Akt, and TGF-β in the treatment regions are up-regulated and the expression levels of miR-29a mRNA are down-regulated compared to the Region A. The hybridization tests showed that changes of the expression of type III pre-collagen, Akt gene, miR-29a gene, and TGF-β gene across the experiment regions are all significantly different in the third week, and the expression levels of them all achieve the highest value in the third week, the expression level of miR-29a gene achieves the lowest value in the third week, which are consistent with the results of real-time quantitative PCR. Conclusion: It is indicated that the combination region of Vitamin A acid and fractional laser may lead to low expression of miR-29a, thus the inhibition of downstream Akt activation is loss, Akt activation is enhanced, enhancement of the expression of TGF-β is induced, leading to proliferation of fibroblasts, and promotion of the collagen proteins’ synthesis in skin. Therefore miR-29a/Akt/TGF-β signal pathway may participate in the skin rejuvenation mechanism of action Vitamin A acid and fractional laser. This may provide a new treatment approach for skin rejuvenation.     

Artificial human skin: cytokine, prostaglandin, Hsp70 and histological responses to heat exposure

Artificial human skin, Skin²™ (keratinocytes and fibroblasts) and EpiDerm™ (keratinocytes), was used to determine heat-induced release/accumulation of mediators of injury and repair. Skin² was exposed to 37 or 41–45°C for 90 min, followed by 37°C for 22.5 h. Media were analyzed for interleukin-1 (IL-1), prostaglandin-E₂ (PGE₂), thromboxane-B₂ (TxB₂) and nuclear matrix apparatus protein (NMAP, viability). Specimens were taken for microscopy. Media and lysates from Skin² and EpiDerm (37 and 45°C) were analyzed for IL-1, its soluble receptor (sIL-1RII), receptor antagonist (IL-1Ra), interleukin-6 (IL-6) and heat shock protein-70A (lysates only). Significant release of IL-1 and PGE₂ was detected only above 43°C, where viability deteriorated and histological damage (especially to keratinocytes) was observed. With both skin products, sIL-1RII release was heat-depressed. IL-1 and IL-1Ra were elevated in media and IL-1Ra appeared to lower the bioactivity of IL-1. Heat depressed IL-6 release from Skin² fibroblasts. IL-6 production and release were negligible with EpiDerm. Heat increased Hsp-70A in both products. We conclude keratinocytes and fibroblasts are not primary cytokine and prostaglandin sources in heatstroke (<44°C) but could be in evaporative cooling failure, focal hot spots, or systemic responses. Levels of IL-1Ra, PGE₂ and Hsp70A may be important markers of cell status.     

Molecular changes during skin aging and wound healing after fractional ablative photothermolysis

Photo‐damaged skin is characterized by major alterations of the extracellular matrix and collagen network, leading to clinically obvious signs of skin aging. UV radiation increases the levels of matrix metalloproteinase (MMP) 1, which initiates the cleavage of fibrillar collagen types I and III. The developing collagen fragments are further degraded by MMPs 2 and 9. Various ablative, non‐ablative, thermal and non‐thermal rejuvenation modalities have been tested for their capacity to reverse epidermal and dermal signs of photo‐ and chronological‐aging. Light and laser therapies are among the most effective treatment options for skin rejuvenation. Conventional laser therapy treats entire surface areas by selective photothermolysis or ablation. Recently, intervention with a fractional ablative laser leads to fast wound healing, and hence, a substantial amount of the target skin area is left untreated. It is not known if the efficacy of a particular ablative skin rejuvenation treatment depends on the extent of microwounding and/or the amount of heat produced. The underlying molecular changes are not fully understood but have been postulated to be induced by time‐dependent changes in heat shock proteins, transforming growth factor β, MMPs, hyaluronic acid synthethases, hyaluronidases and HA, among others.     

Elderly skin and its rejuvenation: products and procedures for the aging skin

In the last few decades, there has been a substantial increase in the population of people over 60 years of age. Most of them maintain a good general health and physical activity and fitness. For these individuals there is a good number of dermatologic procedures, medications, and cosmetics that can be prescribed to improve the aspect of skin aging, providing an improvement in their self-esteem and quality of life as a result of their better look. We will discuss the mechanisms of skin aging, and the procedures and substances used to minimize its deleterious effects, such as sunscreens, estrogens, chemical peels, toxin botulinum, fillers and surgical procedures, among others. The use of makeup and the adverse reactions to cosmetics will also be mentioned.     

Induction of connective tissue growth factor expression by sphingosylphosphorylcholine in cultured human skin fibroblasts

Sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid metabolite that can enhance wound healing. In an effort to find downstream effectors of SPC, we performed microarray analysis and found that the expression of the gene for connective tissue growth factor (CTGF) was significantly affected in human skin fibroblasts cultured in vitro. Northern blot analysis showed that SPC markedly induced CTGF mRNA expression in a dose- and time-dependent manner. Consistent with this result, Western blot analysis also showed that SPC significantly induced the CTGF production. Pretreatment with cycloheximide did not prevent the CTGF induction by SPC, indicating that SPC stimulates CTGF mRNA expression without the increased synthesis of a regulatory protein. Inhibition by pretreatment with Y27632, but not by PD98059 (a mitogen-activated protein kinase 1/2 inhibitor) and LY294002 (a phosphatidylinositol 3-kinase inhibitor), indicated that rho-kinase pathway was involved in SPC-induced CTGF expression. Together, these results reveal the potential importance of CTGF induction as a downstream event in SPC-induced cellular responses.     

Safety and efficacy of human platelet extract in skin recovery after fractional CO2 laser resurfacing of the face: A randomized,controlled, evaluator-blinded pilot study

Background

Fractional carbon dioxide (CO₂) laser resurfacing is used successfully for facial rejuvenation. Post procedure skincare is a variable that influences downtime caused by pain/tenderness, erythema, crusting, and bruising.

Aims

The primary objective of this pilot study was to demonstrate the benefits of human platelet extract (HPE) (plated)™ CALM Serum, a new topical cosmetic product, following fractionated CO₂ ablative laser resurfacing treatment to the entire face versus standard of care.

Methods

In a single-center, randomized, evaluator-blinded pilot study, a total of 18 subjects were randomized into two groups, CO₂ facial resurfacing followed by post-procedural standard of care (Stratacel silicone gel) or CO₂ facial resurfacing with the addition of HPE renewosomes in the CALM Serum.

Results

CALM Serum demonstrated statistically significant less crusting at Day 10 compared to the control group (p = 0.0193) with less downtime in the first 14 days (p = 0.03). Subjects treated with CALM Serum had statistically significant brighter appearing skin at 14 days (p = 0.007) and more youthful looking skin on Days 14 and 30 (p = 0.003 and 0.04, respectively).

Conclusions

This study demonstrates that Renewosome™ technology provides statistically significant post-laser clinical recovery over silicone gel for reducing crusting, and downtime. Subjects reported less diary days of symptoms of pain/tenderness, redness, crusting/flaking, bruising, and itching in the first 14 days compared to the control group. CALM also demonstrated statistically significant improvements in brighter and more youthful appearing skin. CALM is safe and well tolerated.