Efficacy and tolerability of a novel cosmetic growth factor serum when used as part of biweekly diamond tip hydradermabrasion treatments on facial skin

Growth factor preparations have demonstrated effectiveness in reversing age‐related changes in facial skin. TNS® Advanced+ Serum (TNS A+ Serum; SkinMedica®, Allergan Aesthetics, an AbbVie Company) and TNS Advanced+ Pro‐Infusion Serum for DiamondGlow® (DG‐TNS A+; Allergan Aesthetics) combine growth factor technology with active botanical ingredients to target signs of skin aging.


| INTRODUC TI ON
Much of aesthetic medicine is devoted to reversal or amelioration of the visual and tactile signs of aging skin.Skin aging reflects the contribution of intrinsic factors (i.e., reduced production of extracellular matrix [ECM] components, including collagen and elastin) as well as the principal extrinsic factor, exposure to solar ultraviolet light (photoaging).[3] Consistent with these mechanisms, topical application of human fibroblast-generated growth factors has demonstrated the ability to rejuvenate aging skin.5][6] In vitro, such mixtures stimulated greater increases in gene expression of key skin repair genes (coding for collagen proteins and elastic fibers), compared with non-fibroblast-generated growth factors or preparations without growth factors. 7In clinical studies, preparations based on conditioned media containing these growth factors repaired photodamaged facial skin and reduced signs of facial aging, such as lines and wrinkles 3,4,[6][7][8] Subsequently, next-generation growth factor preparations were generated by culturing human neonatal fibroblasts under reduced oxygen tension (i.e., 1%-5%) resembling the intrauterine environment, which induces an apparent phenotypic dedifferentiation into cells exhibiting properties of multipotent stem cells, as revealed by significant changes in the observed secretome.[12][13][14] TNS® Advanced+ Serum (TNS A+ Serum; SkinMedica®, Allergan Aesthetics, an AbbVie Company, Irvine, CA, USA) is a novel topical hypoxic growth factor serum product containing HCCM in combination with active botanical ingredients; its development and components are described in a separate manuscript. 10In clinical studies, TNS A+ Serum has demonstrated the ability to significantly improve multiple hallmarks of aging skin (e.g., photodamage, sagging, coarse lines and wrinkles, and fine lines and wrinkles); whereas in an in vitro human skin model, TNS A+ Serum upregulates ECM-associated genes. 10In addition, TNS A+ Serum improves multiple skin quality parameters when used as monotherapy to reverse photoaging symptoms in postmenopausal women or as part of a post-procedural topical regimen following injection of facial fillers or neuromodulators. 13amondGlow® (DG; Allergan Aesthetics, an AbbVie Company) is a noninvasive, in-office hydradermabrasion procedure that uses a proprietary diamond tip skin-resurfacing technology to simultaneously exfoliate, extract, and infuse targeted pro-infusion serums into the skin to provide customized treatment of specific skin concerns.
We conducted an open-label study to evaluate the efficacy and or females 36-65 years of age with moderate to severe scores (4-7 on the modified Griffiths scale) for coarse lines and wrinkles, firmness, skin smoothness, radiance, and photodamage.Potential subjects were excluded if they had had facial treatments during the 6 months preceding study entry; were nursing, pregnant, or planning to become pregnant during the study; had a history of skin cancer within the past 5 years; had known allergies to skin care products; had a preexisting or dormant dermatologic condition (e.g., psoriasis, eczema, rosacea, or seborrheic dermatitis); or were using prescription medications for acne or skin-lightening, or anti-wrinkle products.
Each subject underwent a series of 6 biweekly (at baseline and through week 10) in-office DG procedures applied to the entire neck and face using DG-TNS A+ Serum.From day 1 through week 12, each subject applied to the face only a twice-daily athome regimen incorporating TNS A+ Serum (at-home formulation) applied as a thin layer to the entire face (am/pm), Facial Cleanser (am/pm), Ultra Sheer Moisturizer (am/pm), and Essential Defense Mineral Shield SPF 35 (am and as needed).Subjects were instructed to avoid extended periods of sun exposure and to wear protective clothing.Assessments were conducted at study visits at baseline (pre-procedure); immediately following (15 ± 5 min) the initial DG procedure; on Day 3; and preceding DG procedures at Weeks 2, 4, 6, 8, and 10; and at Week 12.
The study was approved by the institutional review board (Advarra IRB, Columbia, MD, USA) at the study center on June 9, 2020 (Pro00054717), and was conducted in compliance with all applicable guidelines for the protection of human subjects for research as outlined in 21 CFR 50 and the accepted standards for Good Clinical Practice.All subjects provided written informed consent prior to study enrollment.

| Assessments
At each visit, investigators clinically graded facial fine lines and wrinkles, coarse lines and wrinkles, firmness (visual), skin smoothness-visual, skin smoothness-tactile, skin tone evenness, hyperpigmentation, photodamage, and radiance using a modified All subjects completed sponsor-provided self-assessment questionnaires immediately after the first DG plus DG-TNS A+ procedure and at Day 3 and Weeks 2, 4, 6, 8, 10, and 12. Self-assessment questionnaires addressed treatment effects for facial skin and for neck skin, consisting of statements to which subjects responded "Strongly Agree," "Agree," "Disagree," or "Strongly Disagree."Subjects also rated their overall satisfaction with treatment of the face on a 4point scale (1 = very satisfied; 2 = moderately satisfied; 3 = slightly satisfied; or 4 = not satisfied at all).

| Statistical analysis
All analyses were conducted on the intent-to-treat (ITT) population, defined as all subjects who received treatment and had at least 1 post-baseline evaluation.Efficacy and tolerability parameters were assessed using the Wilcoxon signed rank test, and Corneometer results were assessed using the paired t test; all tests for significance were two-sided at significance level α = 0.05.

| Study population
A total of 29 women enrolled, and 24 completed the study.Reasons for discontinuation included requested withdrawal (n = 3), lost to follow-up (n = 1), and adverse event (n = 1).Demographics and baseline characteristics of the study population are summarized in Table 1.
Most subjects were White or African American; median age was 35 years (range, 25-65 years).Fitzpatrick skin types II-VI were represented, with roughly equal proportions of Fitzpatrick types II-V, and one subject with Fitzpatrick type VI.

| Investigator assessments
Immediately following the initial DG plus DG-TNS A+ procedure and at Day 3, statistically significant improvements versus baseline were observed in mean investigator ratings for fine lines and wrinkles, tactile skin smoothness, and radiance (Figure 1).Statistical significance over baseline was also achieved for visual skin smoothness immediately after the first DG plus DG-TNS A+ procedure and for skin tone evenness and hyperpigmentation at Day 3 post-procedure.
From Week 2 through Week 12, all the nine investigator-assessed skin quality parameters demonstrated progressively increasing mean improvements over baseline (Figure 1).Significant improvements versus baseline were observed by Week 2 for fine lines and wrinkles, skin smoothness (visual and tactile), skin tone evenness, radiance, and hyperpigmentation; by Week 4 for firmness and photodamage; and by Week 6 for coarse lines and wrinkles.

| Self-assessment questionnaires
In general, there was strong agreement throughout the study with positive statements about treatment effects.Immediately after the initial DG plus DG-TNS A+ procedure and at Day 3, high rates of subject agreement were noted for several parameters of treatment effectiveness of the face, including >80% agreement with positive statements on visual/tactile skin qualities (radiance, smoothness, softness, hydration, and refreshed look) (Figure 2).All subjects (100%) agreed that they would get the treatment again, and all would recommend it to a friend.
Rates of subject agreement with selected statements regarding treatment effects on facial skin during Weeks 2 through 12 are summarized in Figure 3.By Week 2, >80% of subjects agreed or strongly agreed with most statements regarding improvement in specific skin attributes; while at Weeks 6 and 12, >90% agreed with statements such as "made my skin look more firm," "helped improve my skin hydration," "made my skin look radiant," "made my skin feel smooth and soft," and "improved the evenness of my skin tone."By Week 6, there was also strong (>80%) agreement about how improvements in these attributes translated into general skin appearance, including statements such as "gave my skin a healthy glow," "rejuvenated the look of my skin," and "made my skin look more youthful or younger looking."Most subjects also agreed or strongly agreed that they preferred the DG plus DG-TNS A+ procedure combined with at-home TNS A+ treatments over other anti-aging facial treatments, and that they would recommend the treatment to a friend.
With respect to neck skin (which received TNS A+ treatment only as part of biweekly DG procedures and not via topical application twice daily), there was also substantial (>85%) agreement with positive statements about skin quality, including "made skin appear firmer," "reduced the look of horizontal and vertical lines on the neck," and "made my neck skin look rejuvenated." At all study visits from Week 2 through Week 12, 100% of subjects reported overall satisfaction with the DG plus DG-TNS A+ procedure combined with twice-daily at-home application of TNS A+ Serum.

| Photographic evidence
Representative

| Safety and tolerability
The mean tolerability ratings for both investigator-rated and subjectrated irritation parameters were well below "Mild" (score of 1) for all parameters and near zero for most.The only significant deviation from baseline was a (not-unexpected) increase in erythema at the immediate post-procedure assessment (p = 0.002) but the mean value (0.41) still remained well below 1 ("Mild").
There was 1 (nonserious) adverse event, perioral dermatitis, which was judged as mild in severity and as possibly related to treatment that resulted in subject discontinuation.All other reported adverse events were based on a temporal association with procedures/treatments, with an unlikely causal relationship attributed to the procedure or treatment.

| DISCUSS ION
As the primary interface with the outside world, one's face is also a key component of self-image and identity. 15,16[17] A single DG plus DG-TNS A+ procedure produced, within

| CON CLUS IONS
This study showed that a restorative facial regimen combining biweekly DG plus DG-TNS A+ in-office procedures with a daily athome skincare regimen using TNS A+ Serum growth factor-based topical treatment is well tolerated and produced substantial improvements in multiple skin parameters.In particular, the improvements in firmness and photodamage were suggestive of extensive repair/restoration with respect to the underlying factors that produce typical signs of skin aging.
tolerability of biweekly DG skin-resurfacing treatments using TNS Advanced+ Pro-Infusion Serum with HCCM growth factor technology (DG-TNS A+; SkinMedica, Allergan Aesthetics, an AbbVie Company) in combination with an at-home topical growth factor serum (TNS A+ Serum) in women with moderate to severe overall facial photodamage.2 | ME THODS 2.1 | Study Design This was a 12-week, open-label, single-center, single-arm clinical study conducted from June 2021 to November 2021.Females aged 25-65 years, inclusive, with Fitzpatrick skin types I-VI and mild to severe overall photodamage to the face, were eligible for inclusion under the following age range guidelines: females 25-35 years of age with mild to moderate scores (3-6 on the modified Griffiths scale, where 0 = none and 9 = severe) for fine lines and wrinkles, skin smoothness, radiance, and photodamage;

Griffiths 10 -
point scale, as none (score of 0, best possible condition), mild (1-3), moderate (4-6), and severe (7-9, worst possible condition).Facial skin hydration was assessed in triplicate on the center of each subject's right or left cheek using a Corneometer CM 825 (Courage + Khazaka electronic GmbH, Köln, Germany).Clinical-grade digital imaging of facial skin was conducted using the VISIA-CR photo station (Canfield Imaging Systems, Fairfield, NJ, USA) and a Canon Mark II digital camera (Canon Incorporated, Tokyo, Japan).

F I G U R E 1
photographs of selected subjects at baseline and posttreatment are shown in Figures 4-6.The corresponding figure legends describe the areas/attributes of concern and the observed improvements.Change from baseline in investigator-assessed facial skin quality parameters for all time points throughout the study.DG, DiamondGlow; TNS A+, TNS Advanced+ Serum.*p < 0.05 vs baseline; † p < 0.01 versus baseline.

F I G U R E 2 F I G U R E 3
Proportion of subjects who agreed or strongly agreed with the listed statements regarding their facial skin immediately following the initial DiamondGlow plus DiamondGlow-TNS Advanced+ Serum procedure and at Day 3. *p < 0.05, † p < 0.01, ‡ p < 0.001, agreed/strongly agreed versus disagreed/strongly disagreed.Proportion of subjects who agreed or strongly agreed with the listed statements about facial skin from Week 2 through Week 12.
photodamage byWeek 4; and in all other parameters by Week 8.10 In women with moderate to severe facial photodamage who underwent facial injections (neuromodulators and/or hyaluronic acid filler), application of a 12-week TNS A +-based skincare regimen