A comprehensive review of the medical and cosmetic applications of exosomes in dermatology.

BACKGROUND: Exosomes are a subset of extracellular vesicles that are released by all cell types and are theorized to play a crucial role in intercellular communication. Ranging from 40 to 160 nm in diameter, exosomes contain a variety of genetic materials including DNA, RNA, mRNA, metabolites, proteins, and lipids depending on their cellular origin. AIM: Given that intercellular communication is abetted by the exchange of cellular components via exosomes, their applied use can have important implications for disease pathology and exosome-based therapeutics. We provide a comprehensive review of the current application of exosomes in medical (and skin) diseases and in cutaneous medical aesthetics. METHODS: A literature search was conducted on PubMed reviewing exosomes and their application in medical and aesthetic fields. RESULTS: While the therapeutic use of exosomes in the treatment of medical and cosmetic dermatological procedures is promising, it is also important to note that most studies implementing exosomes as therapeutic agents have been conducted in preclinical models, thus highlighting the need for additional studies and clinical trials. One more important note in the aesthetic world associated with exosomes is that in the United States, at the time of this writing, exosomes may only be topically applied and not injected into the skin, as is done in many countries worldwide. CONCLUSION: There is a need for additional studies and clinical trials to evaluate the safety and therapeutic effect and safety of exosomes in medical and aesthetic fields.

Validating the Reliability and Clinical Relevance of a Nasolabial Fold Photonumeric Scale.

BACKGROUND: The use of tissue fillers to treat age-related deepening of the nasolabial fold (NLF) has increased and become the standard clinical approach, creating a need for evidence-based, objective evaluation for pre- and post-procedure assessment of the NLF. METHODS: A 5-point rating scale was developed to assess the NLF, specifically the presence of depression and shadowing. Live validation of the scale was performed with a total of 73 participants representing the full range of NLF severities. Physicians board-certified in a core aesthetic specialty (3 trained raters) performed the scale validation over 2 rounds, 2 weeks apart. Training was carried out, and test-retest reliability was quantitated through the determination of intra- and inter-rater reliability by percentage of agreement, weighted kappa statistic with 95% confidence interval (CI), and intraclass correlation coefficient with 95% CI. To evaluate the clinical relevance of a 1-grade difference, rater assessments of 90 photo pairs were compared with previous designations of clinically different or not clinically different. RESULTS: The NLF scale achieved near-perfect intra- and inter-rater reliability when utilized by trained raters to assess a diverse group of live participants. Furthermore, clinically relevant differences between grades were established, and a 1-point difference was detectable by trained evaluators using the NLF scale. CONCLUSION: The clinically relevant and highly reliable validated NLF scale provides a standardized grading system with a user-friendly design for objectively assessing NLF in clinical practice and as a research tool for clinical approval studies of new aesthetic products and technologies. J Drugs Dermatol. 2024;23(1):1284-1291.   doi:10.36849/JDD.7316.

The Role of Calcium Hydroxylapatite (Radiesse) as a Regenerative Aesthetic Treatment: A Narrative Review.

For decades, a wide variety of natural and synthetic materials have been used to augment human tissue to improve aesthetic outcomes. Dermal fillers are some of the most widely used aesthetic treatments throughout the body. Initially, the primary function of dermal fillers was to restore depleted volume. As biomaterial research has advanced, however, a variety of biostimulatory fillers have become staples in aesthetic medicine. Such fillers often contain a carrying vehicle and a biostimulatory material that induces de novo synthesis of major structural components of the extracellular matrix. One such filler, Radiesse (Merz Aesthetics, Raleigh, NC), is composed of calcium hydroxylapatite microspheres suspended in a carboxymethylcellulose gel. In addition to immediate volumization, Radiesse treatment results in increases of collagen, elastin, vasculature, proteoglycans, and fibroblast populations via a cell-biomaterial-mediated interaction. When injected, Radiesse acts as a cell scaffold and clinically manifests as immediate restoration of depleted volume, improvements in skin quality and appearance, and regeneration of endogenous extracellular matrices. This narrative review contextualizes Radiesse as a regenerative aesthetic treatment, summarizes its unique use cases, reviews its rheological, material, and regenerative properties, and hypothesizes future combination treatments in the age of regenerative aesthetics.

Validating the Reliability and Clinical Relevance of an Infraorbital Hollow Photonumeric Scale.

Background: Infraorbital hollowing is a facial aesthetic issue for which a broad age range of patients seek treatment. Expanding treatment options for this region warrants the development of validated tools to objectively assess infraorbital hollow (IOH) severity before and after treatment. Objectives: To validate a 4-point rating scale to assess depression of IOH, depression relative to the mid-pupillary line, and visibility of the lateral orbital rim. Methods: The IOH scale described herein was developed and subjected to live validation with a total of 73 patients representing the full range of IOH severities. Scale validation was performed by board-certified plastic surgeons and dermatologists (3 raters) over 2 rounds, 2 weeks apart. Intrarater and interrater reliabilities were used to demonstrate test-retest reliability as quantitated with percentage of agreement, weighted kappa statistic with 95% confidence interval (CI), and intraclass correlation coefficient with 95% CI. The clinical relevance of a 1-grade difference was evaluated by comparing rater assessments of 77 photo pairs with their previously determined designation as "clinically different" or "not clinically different." Results: The IOH scale demonstrated substantial to near-perfect intrarater and interrater reliabilities when utilized by trained raters to assess a diverse group of live patients. Furthermore, clinically relevant differences between grades were established, and detection of a 1-point difference could be achieved by trained evaluators using the IOH scale. Conclusions: This highly reliable, clinically relevant, and validated IOH scale provides a user-friendly, standardized grading system to objectively evaluate and track changes in infraorbital hollowing in clinical practice and research.

Novel, Validated 5-Point Photonumeric Scales for Assessment of the Neck and Décolleté.

BACKGROUND: There is a scarcity of scales that assess platysmal bands, wrinkles in the décolleté, and horizontal neck lines in the digital and live setting. OBJECTIVES: The objective of this investigation was to create and validate 5-point photonumeric scales that assess horizontal neck lines, platysmal bands, and wrinkles in the décolleté. METHODS: A medical team created 3 different novel 5-point photonumeric scales for the assessment of horizontal neck lines, platysmal bands, and décolleté wrinkling. Eleven international raters were involved in the digital validation, and 4 raters performed a live validation. RESULTS: The Croma (Leobendorf, Austria) Horizontal Neck Lines Assessment Scale showed substantial interrater agreement and almost perfect intrarater agreement in the digital and live validations, respectively. The Croma Platysmal Bands Assessment Scale showed substantial intrarater agreement in both digital and live validations. For the décolleté, a static scale and a dynamic scale were created and validated. The Croma Static Décolleté Wrinkles Assessment Scale showed substantial and almost perfect interrater agreement in the digital and live validations, respectively, and the intrarater agreement in both was almost perfect. The Croma Dynamic Décolleté Wrinkles Assessment Scale showed almost perfect agreement in both validation settings for both interrater and intrarater measures. CONCLUSIONS: The Croma Horizontal Neck Lines Assessment Scale and the Croma Static and Dynamic Décolleté Wrinkles Assessment Scales have sufficient interrater and intrarater agreement for justifiable use in clinical and research settings.

Treatment of Upper Facial Lines With DaxibotulinumtoxinA for Injection: Results From an Open-Label Phase 2 Study.

BACKGROUND: Simultaneous treatment of moderate-to-severe upper facial lines is reflective of real-world clinical practice. OBJECTIVE: To evaluate the efficacy and safety of daxibotulinumtoxinA-lanm for injection (DAXI) for simultaneous treatment of glabellar, forehead, and lateral canthal (LC) lines. METHODS: In this open-label, single-arm Phase 2 study, patients (48 enrolled, 94% completed, follow-up 24-36 weeks) received DAXI 40U (glabellar), 32U (forehead), and 48U (LC) lines. Key efficacy endpoints: percentages of patients achieving none/mild wrinkle severity (investigator-rated) for each upper facial line scale at Week 4. RESULTS: At Week 4, most patients achieved none/mild wrinkle severity (investigator-rated): glabellar (96%), forehead (96%), and LC (92%). Median times to loss of none/mild response (investigator- and patient-rated) among all patients were: 24.6 (glabellar), 20.9 (forehead), and 24.9 (LC) weeks; and 25.0, 24.0, and 28.1 weeks, respectively, among Week-4 responders. At Week 4, most patients reported improvements (Global Aesthetic Improvement Scale: 96%-98%) and high satisfaction rates (85%-98%). Five patients experienced treatment-related adverse events: injection-site erythema (3 patients/7 events), facial discomfort (2 patients/2 events), and headache (1 patient/1 event). No patients experienced eyebrow or eyelid ptosis. CONCLUSION: Simultaneous treatment of upper facial lines with DAXI was well tolerated and demonstrated high response rates, extended duration, and high patient satisfaction. CLINICAL TRIAL REGISTRY: https://clinicaltrials.gov/ct2/show/NCT04259086.

Supplement Individual Article: Algorithm for Pre-/Post-Procedure Measures in Racial/Ethnic Populations Treated With Facial Lasers, Nonenergy Devices, or Injectables.

BACKGROUND: Cosmetic procedures with lasers, nonenergy devices, and injectables are increasing in popularity among patients with skin of color. Published algorithms address measures to reduce side effects related to aesthetic procedures; however, none focus on reducing adverse events in skin of color. METHODS: An expert panel of dermatologists and plastic surgeons conducted face-to-face and online meetings to develop an algorithm for measures before, during, and after using aesthetic devices (energy and nonenergy-based) and injectable treatments based on the best available evidence for skin of color. Published algorithms and literature searches for aesthetic procedures provided guidance for the current algorithm. A modified Delphi method was used to reach a consensus to apply outcomes of literature searches, along with expert opinion, resulting in the current algorithm. RESULTS: The four sections of the algorithm outline an approach to optimize outcomes with specific before, during, and after procedure considerations. Pre-procedural consultation includes the development of a specific treatment plan based on individual patient goals and risk profile (including history and signs that may predict a higher risk for pigmentary or scarring complications). Before the procedure, sun avoidance and sunscreen use are emphasized; herpes simplex virus 1 prophylaxis and bleaching agents are administered if indicated. During the procedure, skin cleansing products are addressed, along with judicious techniques to minimize unintended cutaneous injury or inflammation. Post-procedural sunscreen and gentle skincare that may include skin-lightening agents or formulations designed to prevent infection and promote optimum healing are advised. CONCLUSIONS: The algorithm strives to optimize treatment outcomes for patients with skin of color by providing their physicians with guidance on measures before, during, and after office-based medical aesthetic procedures. J Drugs Dermatol. 2022;21:9(Suppl 1):s3-10.

The Future of Contract Research Organizations in Dermatology and Aesthetic Research.

Objective: Dermatology and aesthetic medicine has experienced significant growth in recent years, driven by industry-sponsored research performed by clinical investigators. Contract research organizations (CROs) play an important role to ensure clinical trials are run efficiently, ethically, and according to Good Clinical Practice. An advisory group of dermatologists and aesthetic researchers was assembled to obtain feedback about CRO experiences for developing a "next-generation" specialty CRO for dermatology and aesthetic medicine. Methods: Experienced dermatologists and aesthetic physician researchers convened during the 2022 Winter Dermatology Annual Meeting in Kauai, Hawaii, to discuss experiences and make suggestions regarding CROs. Topics included positive and negative aspects of CRO experiences, desirable CRO services, and how CROs can be improved. Results: Benefits of working with CROs include project, data, and resource management and availability of technology. Desired functions include rapid study start-up, subject recruitment, and accurate and organized site-related documentation. Other qualities include access to large subject populations close to study locations, use of CRO-based clinical research assistants to support principal investigators across study sites, and scientific consultation, protocol development, medical writing, project management, clinical and medical monitoring, data management, biostatistics, and pharmacovigilance. Conclusion: CROs serve a vital role in the development process of drug, device, and therapeutics; however, it is important that changes to traditional CRO models are made to provide improved interactions with researchers in dermatology and aesthetic medicine.

Creating Lift in the Lower Face With Botulinum Toxin A Treatment: An Anatomical Overview With Videos and Case Studies Illustrating Patient Evaluation and Treatment.

Background: Relaxation of depressor muscles in the lower face with botulinum toxin A (BoNT-A) can create a lifting effect and dramatically improve jawline contour and resting facial expression. Even with the recent increase in interest in lower face rejuvenation, BoNT-A is a relatively under-recognized tool for treatment of this area. When treating the lower face, an understanding of anatomy and the relationship between the facial muscles is especially important, as injection patterns must be customized for consistently positive outcomes. Objectives: This study was aimed to provide basic knowledge of the activities of the muscles in the lower face and neck and to describe the basis for injecting BoNT-A to create lift in this area. Expert guidance for injection is also provided. Methods: As part of a continuing medical education course on differentiating botulinum toxin products, a panel of 4 expert physician injectors participated in a live webinar to discuss the implications of increasing toxin use. Results: The practical guidance in this manuscript is based on the most frequently requested information by audience members and the information considered critical for success by the authors. The authors outline the functional anatomy of the lower face most relevant for BoNT-A treatment and case studies as well as methods for patient evaluation and injection technique are also provided. Videos showing treatment planning and injection technique for the lower face and neck are included. Conclusions: BoNT-A is an important nonsurgical tool for creating lift in the lower face.

Subject satisfaction and psychological well-being with escalating abobotulinumtoxinA injection dose for the treatment of moderate to severe glabellar lines.

BACKGROUND: Previous studies indicate that the efficacy and durability of a single AbobotulinumtoxinA (ABO) treatment for moderate to severe glabellar lines may be enhanced with increasing dose, while safety outcomes remain consistent with those of the licensed dose (50 U). AIMS: Evaluation of subject-reported indicators of treatment efficacy, satisfaction, and psychological well-being with ABO dose escalation. METHODS: A Phase 2, 36-week, multicenter, randomized, dose-ranging, double-blind, placebo-controlled study was conducted in adults with moderate to severe glabellar lines. Subjects received a single ABO treatment, dosed at 50, 75, 100, or 125 U, or placebo. Efficacy endpoints comprised subject-assessed improvement in line severity of ≥1-grade from baseline at maximum frown, global aesthetic improvement scale (GAIS) grade, FACE-Q™ appraisal of lines, psychological well-being and age, and subject satisfaction. RESULTS: The study included 399 subjects (88.2% were female). Respective responder rates (≥1-grade improvement) with ABO 50-125 U doses ranged between 96.3%-100% at Week 4, 65.0%-67.9% at Week 24, and 33.8%-44.4% at Week 36. GAIS responder rate and FACE-Q appraisal of lines showed a similar pattern of change. Satisfaction was high and psychological well-being was improved from Week 4 through Week 36, with natural, youthful, and refreshed appearance reported for all ABO doses. CONCLUSIONS: A single ABO treatment (dosed at 50-125 U) provided significant and sustained improvements in glabellar line severity over durations up to 36 weeks, versus placebo. Treatment satisfaction was high with all doses. Participants reported natural and youthful appearance, alongside improvements in psychological well-being.

Skin Tightening With Hyperdilute CaHA: Dilution Practices and Practical Guidance for Clinical Practice.

BACKGROUND: Over the past several years, hyperdilute calcium hydroxylapatite (CaHA) has emerged as an effective modality for improving skin quality and managing laxity in the face, arms, hands, neck, décolletage, upper arms, abdomen, buttocks, and upper legs, as well as for treating cellulite and striae. Whereas undiluted CaHA is used to provide volume, hyperdilute CaHA is distributed across a much larger surface area in a more superficial plane to stimulate neocollagenesis and elastin formation over time. The absence of lymphocytic infiltrates and predominance of type 1 collagen in the tissue response to CaHA make hyperdilute CaHA a valuable tool for nonsurgical skin tightening. OBJECTIVES: The aim of this study was to provide practical step-by-step guidance on patient selection, dilution practices, and optimal injection technique to facilitate incorporation of the technique into clinical practice. METHODS: Over the course of 3 regional meetings in the United States, 12 expert physician injectors participated in live webinars as part of a continuing medical education program. RESULTS: The practical guidance in this manuscript is based upon the most frequently requested information by audience members and the information considered critical for success by the authors. CONCLUSIONS: The minimally invasive nature of filler injection results in little downtime, making this treatment particularly appealing. The recommendations presented are consistent with previously published consensus guidelines on hyperdilute CaHA but are intended to serve as "how-to" guidance based on the experience of expert injectors who have successfully treated the face and body.

Barbed Polydioxanone Sutures for Face Recontouring: Six-Month Safety and Effectiveness Data Supported by Objective Markerless Tracking Analysis.

BACKGROUND: Barbed polydioxanone (PDO) sutures allowing for minimally invasive skin lifting are broadly and increasingly used in aesthetic dermatology. OBJECTIVES: To describe utilization of diverse barbed PDO sutures for aesthetic facial corrections in Caucasian patients, to evaluate long-term safety and to demonstrate effectiveness in skin tightening, redefinition of facial contours, and tissue elevation. METHODS: A retrospective chart review of patients routinely treated with barbed PDO sutures on face was performed. Aesthetic improvement was evaluated at 6-, 12- and 24-week posttreatment by the treating physician, patients, and an independent photographic reviewer. Patient's satisfaction with treatment outcome was evaluated. Procedure effects were also objectively measured by markerless tracking analysis. RESULTS: Sixty patients were treated with a total of 388 barbed sutures in various anatomical areas and followed-up for 24 weeks. At Week 24, the aesthetic improvement rate was 80% to 100% (depending on the evaluator), skin movements related to pre-treatment photographs showed significant changes across several different anatomical regions, and 97% of patients were satisfied with the overall treatment outcome. Transient, mild, and short-lasting adverse events, mostly pain and hematoma, occurred in 15% of patients. CONCLUSIONS: Barbed PDO sutures are safe and highly effective for aesthetic corrections, with results lasting for at least 24 weeks.

The Future of Contract Research Organizations in Dermatology and Aesthetic Research.

Objective: Dermatology and aesthetic medicine has experienced significant growth in recent years, driven by industry-sponsored research performed by clinical investigators. Contract research organizations (CROs) play an important role to ensure clinical trials are run efficiently, ethically, and according to Good Clinical Practice. An advisory group of dermatologists and aesthetic researchers was assembled to obtain feedback about CRO experiences for developing a "next-generation" specialty CRO for dermatology and aesthetic medicine. Methods: Experienced dermatologists and aesthetic physician researchers convened during the 2022 Winter Dermatology Annual Meeting in Kauai, Hawaii, to discuss experiences and make suggestions regarding CROs. Topics included positive and negative aspects of CRO experiences, desirable CRO services, and how CROs can be improved. Results: Benefits of working with CROs include project, data, and resource management and availability of technology. Desired functions include rapid study start-up, subject recruitment, and accurate and organized site-related documentation. Other qualities include access to large subject populations close to study locations, use of CRO-based clinical research assistants to support principal investigators across study sites, and scientific consultation, protocol development, medical writing, project management, clinical and medical monitoring, data management, biostatistics, and pharmacovigilance. Conclusion: CROs serve a vital role in the development process of drug, device, and therapeutics; however, it is important that changes to traditional CRO models are made to provide improved interactions with researchers in dermatology and aesthetic medicine.

INDIVIDUAL ARTICLE: Algorithm for Nonenergy and Injectable Treatment Pre-/Post-Procedure Measures.

BACKGROUND: Nonenergy and injectable treatments are frequently used for facial rejuvenation. Many publications have addressed methods to reduce adverse events related to the procedure; however, no algorithm exists on temporol before, during, and after measures for nonenergy and injectable treatments. METHODS: A panel of dermatologists and plastic surgeons convened a virtual meeting to develop an algorithm for measures before, during, and after nonenergy and injectable treatments based on the best available evidence and the panelists' experience and opinion. For the project, a Delphi method was applied, which was adapted from face-to-face meetings to a virtual meeting to discuss the outcome of literature searches to reach a consensus on the algorithm. RESULTS: The four sections of the algorithm address measures for optimizing outcome before, during, and after the procedure. Prevention includes avoiding excessive sun exposure and the use of a broad-spectrum sunscreen with an SPF 30 or higher. Before nonenergy-based and injectable treatments, the avoidance of alcohol, retinol peels, and agents such as acetylsalicylic acid and non-steroidal anti-inflammatory drugs, amongst other agents, is advised. Isopropyl alcohol, chlorhexidine, or hypochlorous acid (HOCl) prepare the skin before nonenergy and injectable treatments. The advisors recognize HOCL as particularly useful as it is active against bacterial, viral, fungal microorganisms and biofilm. The literature is inconsistent about the use of topical agents and skincare before and after the procedure. CONCLUSIONS: The algorithm aims to support an optimal treatment outcome for their patients, providing physicians with guidance on measures before, during, and after nonenergy and injectable treatments. J Drugs Dermatol. 2021;20:11(Suppl):s3-10.

AbobotulinumtoxinA for the Treatment of Moderate-to-Severe Glabellar Lines: A Randomized, Dose-Escalating, Double-Blind Study.

OBJECTIVE: To evaluate the efficacy and safety of AbobotulinumtoxinA (ABO) dose escalation in the correction of moderate-to-severe glabellar lines. DESIGN: Phase 2, 36-week, multicenter, randomized, dose-ranging, double-blind, placebo-controlled study. METHODS: Adults with moderate-to-severe glabellar lines received a single ABO treatment, dosed at 50, 75, 100, or 125 U, or placebo. Primary endpoint was week 4 composite ≥2-grade responder rate among those achieving a severity score of 0 (none) or 1 (mild) at maximum frown, evaluated using concurrent investigator and subject assessments. Secondary endpoints included ≥1-grade severity improvement, duration of effect, and reporting of treatment-emergent adverse events (TEAEs). RESULTS: Overall, 399 subjects were included (88.2% were female). Week 4 composite ≥2-grade ABO responder rate was 80.0% (50 U), 88.8% (75 U), 90.0% (100 U) and 95.1% (125 U), versus 2.6% with placebo (P<0.001). Responder rate (≥1-grade) ranged between 53% (50 U) and 69% (125 U) at week 24 and between 18% (50 U) and 31% (125 U) at week 36. Median time (weeks) to return to baseline severity/worse, among those scoring 0 (none) or 1 (mild), was 32.3 (50 U), 34.3 (75 U), 36.0 (100 U) and 36.6 (125 U), versus 23.7 (placebo). ABO-related TEAEs were reported in 4% of subjects (80% were mild). No seroconversion to ABO neutralizing antibodies was seen. CONCLUSION: A single ABO treatment provided rapid and effective improvements in glabellar line severity at all doses. Higher doses tended to demonstrate elevated response rates and longer duration of effect. All ABO doses were well-tolerated with low TEAE incidence. J Drugs Dermatol. 2021;20(9):980-987. doi:10.36849/JDD.6263.

The Second of Two One-Year, Multicenter, Open-Label, Repeat-Dose, Phase II Safety Studies of PrabotulinumtoxinA for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients.

BACKGROUND: PrabotulinumtoxinA is a 900-kDa botulinum toxin type A produced by Clostridium botulinum. OBJECTIVES: The authors sought to investigate the safety of prabotulinumtoxinA for treatment of glabellar lines. METHODS: This was a multicenter, open-label, repeat-dose, 1-year phase II safety study. Adults with moderate to severe glabellar lines at maximum frown, as independently assessed by both investigator and patient on the validated 4-point photonumeric Glabellar Line Scale (0 = no lines, 1 = mild, 2 = moderate, 3 = severe), were enrolled. On day 0, patients received an initial treatment (IT) of 20 U prabotulinumtoxinA (4 U/0.1 mL final vacuum-dried formulation injected into 5 glabellar sites). On and after day 90, patients received a repeat treatment (RT) if their Glabellar Line Scale score was ≥2 at maximum frown by investigator assessment. Safety outcomes were evaluated throughout the study. RESULTS: The 570 study patients received a median total dose of 60 U, that is, 3 treatments. Sixty-one patients (10.7%) experienced adverse events (AEs) assessed as possibly study drug related; 6.5% experienced study drug-related AEs after the IT. With each RT, progressively lower percentages of patients experienced study drug-related AEs. Eight patients (1.4%) experienced study drug-related AEs of special interest: 5 experienced eyelid ptosis (0.9%), 3 eyebrow ptosis (0.5%), 1 blepharospasm (0.2%), and 1 blurred vision (0.2%). Seven patients (1.2%) experienced serious AEs, but none were study drug related. A total of 4060 serum samples were tested for antibotulinum toxin antibodies; no seroconversion was observed. CONCLUSIONS: The safety of RTs of 20 U of prabotulinumtoxinA for moderate to severe glabellar lines was confirmed in this second phase II study based on a broad range of outcomes.

Understanding Facial Muscle Aging: A Surface Electromyography Study.

BACKGROUND: Facial aging is a multifactorial process that involves all tissues of the face, including skin, muscles, fat, ligaments, and bone. Whereas robust evidence is available for age-related changes of bone and facial fat, the influence of age on facial muscle activity is poorly understood. OBJECTIVES: The objective of this study was to investigate the motor unit action potential of facial muscles by utilizing surface-derived, noninvasive electromyography in young and old healthy volunteers. METHODS: The study investigated a total of 32 healthy volunteers with a mean [standard deviation] age of 42.6 [19.6] years (range, 21-82 years) and a mean BMI of 23.9 [2.7] kg/m2 (range, 18.5-29.7 kg/m2) by performing surface-derived, noninvasive facial electromyography. Nine facial muscles were investigated bilaterally, resulting in a total of 1632 measurements of the signal, baseline noise, and signal-to-noise ratio of these muscles. RESULTS: The results of the study revealed that age does not significantly influence the signal (P = 0.234), the baseline noise (P = 0.225), or the signal-to-noise ratio (P = 0.432) of younger individuals (<30 years) vs older individuals (>50 years) in a gender- and BMI-matched statistical model. Exceptions were the zygomaticus major muscle (reduced activity), procerus muscle (increased activity), and corrugator supercilii muscle (increased activity). CONCLUSIONS: The results of this facial electromyography study may help to increase the understanding of facial aging. Future studies need to reproduce the results presented herein to further increase our understanding of facial aging.

Rheology of Polymethylmethacrylate-Collagen Gel Filler: Physiochemical Properties and Clinical Applications.

BACKGROUND: Soft tissue fillers are comprised of a range of materials with differing physiochemical and rheologic (ie, flow) properties. These properties can inform treatment selection for specific anatomic areas, planes of injection, and clinical applications. OBJECTIVES: The aim of this study was to characterize the rheologic properties of polymethylmethacrylate (PMMA)-collagen gel for comparison with other available fillers. METHODS: Commercially available PMMA-collagen gel, hyaluronic acid (HA), and calcium hydroxylapatite (CaHA) fillers were obtained from their respective manufacturers. Measures of complex viscosity (η*) and elastic modulus (G') for each filler were collected at 0.7 Hz in triplicate according to standard procedures on a rotational rheometer fitted with a 40-mm steel plate at 25°C on a Peltier plate (500-µm gap). RESULTS: The measured η* and G' values for HA and CaHA fillers were in agreement with previously published data. The difference in η* between CaHA (mean [standard deviation], 358.9 [21.56] Pa-s) and PMMA-collagen gel (656.41 [68.03] Pa-s) was statistically significant (P < 0.0001), as was the difference between the G' of CaHA (1424.8 [83.3] Pa) and the G' of PMMA-collagen gel (2815.27 [304.07] Pa; P < 0.0001). CONCLUSIONS: PMMA-collagen gel exhibited the highest η* and G' of all tested fillers. These properties likely underpin an increased capacity for lifting and support in areas where long-lasting revolumization is appropriate. In practice, PMMA-collagen gel is well suited for treatment of acne scars, as well as injection into the supraperiosteal plane in the temple, chin, mandible, and piriform by a retrograde linear threading technique. Additional clinical considerations are discussed.