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AS WE WELCOME A NEW YEAR, WE ARE ALSO STEPPING INTO A NEW ERA of aesthetic medicine; the industry is experiencing an unprecedented transformation. Scientific advancements, cutting-edge biotechnology, and the integration of artificial intelligence (AI) are set to redefine the standards of patient care and treatment outcomes. In this issue, we explore some of the most pressing developments shaping the field today.

The rapid rise of GLP-1 receptor agonists has sparked a revolution in weight management, with profound implications for aesthetic medicine. Initially developed for diabetes treatment, GLP-1 agonists such as semaglutide and tirzepatide have found a new role in non-surgical weight loss. However, rapid weight reduction often comes with aesthetic concerns, such as volume loss and skin laxity. Clinics worldwide are seeing an influx of patients seeking biostimulatory treatments, muscle stimulation, and skin-tightening procedures to counteract these effects. Experts emphasise the need for responsible implementation, ensuring patients receive a holistic approach to weight management that prioritises health and aesthetic balance. For more insights, you can read the full article on page 10.

The combination of GLP-1-induced weight loss and the increasing popularity of buccal fat removal has led to a surge in demand for biostimulatory injectables. Shino Bay Aguilera and Summer Wong discuss how biostimulators such as poly-L-lactic acid (PLLA) and calcium hydroxylapatite (CaHA) offer a long-term solution to facial volume depletion. Unlike traditional hyaluronic acid fillers, these treatments promote collagen production, providing structural support and restoring youthful contours in a more natural way. As the demand for non-surgical rejuvenation continues to rise, biostimulatory treatments are becoming a key tool in the aesthetic practitioner’s arsenal. Read more on page 36.

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International Journal of Aesthetic and Anti-Ageing Medicine

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Editor Balraj Juttla balraj.juttla@informa.com

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Artificial intelligence is revolutionising how aesthetic clinics engage with patients, optimize marketing efforts, and enhance consultations. AI-driven tools now offer hyper-personalised treatment recommendations, advanced facial mapping, and automated patient engagement strategies. However, as AI adoption grows, so do ethical concerns regarding data privacy, misinformation, and authenticity in digital marketing. This issue takes a closer look at how clinics can leverage AI responsibly to improve patient experiences while maintaining credibility and trust. You can read the full article on page 14.

Advancements in regenerative aesthetics are pushing the boundaries of skin and tissue restoration. Experts Aris Sterodimas and Beatriz Nicaretta delve into the integration of stromal-enriched lipograft, helium plasma radiofrequency, and exosome therapy in facial rejuvenation. These innovations not only enhance collagen and elastin production but also improve overall skin health and resilience. With regenerative aesthetics gaining momentum, the future of anti-ageing treatments is shifting towards long-term biological repair rather than temporary cosmetic fixes. Find out more on page 18.

Balraj Juttla Editor, PRIME balraj.juttla@informa.com

January/February 2025

7 FACE 2025: The UK’s premier aesthetic medicine conference returns to London

8 Experts reveal the top 5 trends in aesthetic medicine for 2025

INDUSTRY INSIDER

10 GLP-1: A weight loss revolution reshaping aesthetic medicine

The rise of GLP-1 receptor agonists has revolutionized weight management, dramatically reshaping aesthetic medicine practices. With the potential to improve patient outcomes and boost clinic revenues, experts call for responsible implementation to address both benefits and challenges

14 Practice marketing: The AI effect

Artificial intelligence is changing plastic surgery marketing in ways that help and could hurt a practice’s image. We delve into the potential uses of AI and explore the pitfalls

AESTHETIC FEATURES

18 Advanced use of biotechnology, radiofrequency and exosomes for facial rejuvenation

Aris Sterodimas and Beatriz Nicaretta detail how the integration of advanced modalities such as stromal enriched lipograft, helium plasma RF, and exosome therapy is transforming facial rejuvenation

28 Enhanced facial rejuvenation with poly(l-lactide- co-ε-caprolactone)hyaluronic acid threads

George Sulamanidze, MD, and Igor Gulyaev, MD, describe the results from their 6-month split-face study on the effects of the fourthgeneration of Aptos threads

36 Biostimulatory Injections: Restoring youthful contours after Ozempic and buccal fat removal

With the rise of Ozempic-induced facial volume loss and buccal fat removal procedures, Shino Bay Aguilera and Summer Wong explore the rise of biostimulatory injections as a key solution for restoring youthful contours

42 Recombinant enzymes: a new pathway into facial reshaping and skin rejuvenation

Jan Balczun, MD, highlights the synergistic power of recombinant enzymes in facial reshaping and skin rejuvenation, offering safe, effective, and substrate-specific solutions

46 Injecting neuromodulators into the upper depressor muscles to treat forehead lines

Marcelo Germani, Victor Rogerio, Gabriela Giro, and Victor RM Munoz-Lora present a case study exploring a novel botulinum toxin approach targeting glabellar muscles for smoother foreheads and preserved eyebrow symmetry

50 A round-up of the major industry events around the world over the next 12 months

NEWS

A round-up of news stories in the aesthetic and anti-ageing medicine industry

FACE 2025: THE UK’S PREMIER AESTHETIC MEDICINE CONFERENCE RETURNS TO LONDON

A MUST-ATTEND EVENT FOR AESTHETIC PRACTITIONERS — FREE PASSES ANNOUNCED

FACE, the UK’s premier scientific aesthetic medicine conference, returns to the Business Design Centre, London, on 26–27 June 2025. This year promises unparalleled access to cutting-edge knowledge, including free passes for delegates from the UK and Ireland.

Building on over 20 years of excellence, FACE 2025 is set to deliver the most comprehensive educational programme in the field of minimally invasive aesthetic and anti-ageing medicine. This is a unique opportunity to learn from over 150 world-class national and international speakers, experts you won’t find anywhere else in the UK, sharing the latest scientific advancements, clinical insights, and live demonstrations.

Building on over 20 years of excellence, FACE 2025 is set to deliver the most comprehensive educational programme in the field of minimally invasive aesthetic and anti-ageing medicine.

This two-day event offers delegates at all career stages a chance to refine their skills and expand

their expertise across four focused agendas: Advanced Injectables, Multispecialty Aesthetics, Aesthetics Open Stage, and Industry Workshops. From injectables and regenerative medicine to

threads and business management, FACE covers eight in-depth topics designed to address the core segments of the aesthetic medicine market.

Attendees can expect high-quality scientific content under the supervision of the Aesthetic Multispecialty Society (AMS). FACE 2025 is also an unmissable chance to reconnect with colleagues and grow your professional network within the vibrant aesthetics community.

With free passes available for UK and Ireland delegates, FACE 2025 provides exceptional value, making it accessible to more practitioners than ever. Whether you’re a seasoned expert or just starting your journey in aesthetics, FACE offers something for everyone.

Join us at the Business Design Centre, London, for an unforgettable weekend of learning, innovation, and inspiration.

OLDER AGE LINKED TO COMPLICATIONS AFTER BREAST SURGERY

For women undergoing breast reconstruction after mastectomy, older age is associated with small but significant increases in certain complications, reports a study in the January issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS). The journal is published in the Lippincott portfolio by Wolters Kluwer.

Older women may be less satisfied with the appearance of the reconstructed breasts, but may have better psychologic adjustment after breast reconstruction compared to younger patients, according to the new research by Jonas A. Nelson, MD, MPH, and colleagues of Memorial Sloan

Kettering Cancer Center, New York. ‘These findings clarify how age affects the outcomes of breast reconstruction, which may help in minimising the risks and maximising the benefits for older women considering reconstructive surgery after mastectomy,’ Dr. Nelson comments.

Breast reconstruction has important benefits for women undergoing mastectomy for treatment of breast cancer. Previous studies have suggested that age ‘should not be a deterring factor’ to post-mastectomy breast reconstruction (PMBR), but the true impact of age on patient outcomes remains unclear. While about one-half of patients undergo breast reconstruction after mastectomy, only about 6% are older than 60 years.

Toward ‘a more thorough and rigorous assessment’ of how age affects breast reconstruction outcomes, Dr. Nelson and colleagues analyzed 4,730 patients who underwent PMBR at the authors’ cancer centre between 2017 and 2022. After adjustment for other factors, older patients were at higher risk of three types of complications: infection, breakdown (necrosis) of the skin flap used for reconstruction, and fluid buildup (seroma) under the wound.

For all three complications, risk increased slightly per year of age. For every 10-year increase in age, infection risk increased by 10% while skin necrosis and seroma risk increased by 20%.

CENTRE, LONDON 26-27 JUNE 2025

BUSINESS

DESIGN

Under the scientific supervision of the Aesthetic Multispecialty Society (AMS)

EXPERTS REVEAL TOP 5 TRENDS IN AESTHETIC MEDICINE FOR 2025

PLASTIC SURGEONS IDENTIFY PROCEDURES ON THE RISE IN THE US

The field of plastic surgery and aesthetic medicine continues to evolve, blending science, artistry, and technology to meet patient needs. As 2025 begins, the expert surgeons and founders of Premier Plastic Surgery Partners—Dr Ross Clevens, Dr Steven Ronan and Dr Jeffrey Spiegel—offer insights into the top trends expected to shape the industry in the coming year.

‘With advancements in technology and a growing focus on personalised, natural results, 2025 will be an exciting year for aesthetic medicine,’ says Ross A. Clevens, MD, FACS, a double board-certified facial plastic surgeon and founder of Clevens Face and Body Specialists based in Melbourne and Orlando, Fla. ‘Patients are more informed than ever, and they’re demanding innovation paired with expertise to deliver exceptional results with less downtime.’

Top 5 trends predicted for 2025

1. Preservation and structural rhinoplasty

‘Preservation rhinoplasty with an emphasis on preserving nasal structure and integrity is emerging as a game-changer to provide long term and reliable results for our patients,’ notes Dr Clevens, who is frequently invited to share his expertise at facial plastic surgery meetings around the globe. ‘By conserving the nasal structure rather than removing tissue, this technique delivers beautiful, natural results while reducing recovery time.’

contouring and neck lifts are increasingly in demand. Dr. Jeffrey Spiegel, a globally recognised expert in facial plastic surgery, notes: ‘Patients are seeking subtle yet transformative changes that enhance their confidence on and off the screen.’

Additionally, the deep plane facelift will continue to gain traction. ‘This technique provides more natural and longer-lasting outcomes by repositioning the deeper layers of the face rather than simply tightening the skin,’ says Dr Clevens.

4. Enhanced recovery techniques

Rapid recovery solutions are becoming integral to surgical procedures, with new technologies to minimise downtime. ‘We’re seeing breakthroughs in post-operative care, from advanced pain management to regenerative therapies that accelerate healing,’ adds Dr Ronan.

5. Preventative aesthetic medicine

The younger generation is adopting a proactive approach to ageing. ‘In 2025, more patients in their 20s and 30s will seek treatments such as Botox, skin tightening and fractional laser resurfacing as preventative measures,’ shares Dr Spiegel, founder of The Spiegel Center in Boston. ‘This is about maintaining youthful skin and preventing the need for more invasive procedures later.’

With advancements in technology and a growing focus on personalised, natural results, 2025 will be an exciting year for aesthetic medicine.

2. Personalisation in body contouring

Body contouring is becoming more customised, with technologies like high-definition liposuction, CoolSculpting ELITE and BodyTite tailoured to individual anatomy. ‘Patients want results that look and feel natural, which requires a highly personalised approach,’ says Dr Stephen Ronan, a leader in advanced body sculpting techniques and founder of Blackhawk Plastic Surgery in Danville, Calif., a suburb of nearby San Francisco.

3. Facial optimisation for the digital age With video calls continuing to influence how people perceive themselves, facial optimisation procedures such as chin augmentation, jawline

Meanwhile, injectables will continue to lead the aesthetic market for nonsurgical facial rejuvenation, with a focus on bio-stimulatory fillers and neuromodulators that not only restore volume but also enhance skin health. ‘We’re seeing a shift toward injectables that deliver long-term improvements and collagen-boosting solutions,’ explains Dr Clevens.

A new era of patient-centered care

‘Patients are more educated than ever,’ notes Dr Spiegel. ‘They are seeking not just results but a journey rooted in trust, safety and personalisation.’

As pioneers in the field, Premier Plastic Surgery Partners are committed to staying at the forefront of innovation while delivering the highest level of care, ensuring patients achieve their aesthetic goals in 2025 and beyond.

AMWC 2025 RETURNS ON MARCH 27-29, 2025

The Aesthetic & Anti-Aging Medicine World Congress (AMWC), returns for its 23rd edition on March 27–29, 2025, at the iconic Grimaldi Forum in Monaco. As the world’s premier event in aesthetic and anti-ageing medicine, AMWC 2025 will bring together over 15,000 delegates, 300 speakers, and 900 leading brands from 140 countries, showcasing cutting-edge advancements and evidence-based practices in the field.

AMWC goes beyond traditional conference formats with its exciting AMWC Awards, recognising excellence in clinical practice and innovation in product and device development. Additionally, the Aesthetic Disruptors initiative offers a platform for rising stars in aesthetic medicine, spotlighting the next generation of talent and their groundbreaking research.

This year, AMWC introduces the Aesthetics New Joiners Track, specially designed for practitioners beginning their journey in aesthetic medicine. Directed by Professor Jean-Paul Meningaud, these sessions, held in the Salle en Pinède Room, provide essential training on clinical fundamentals, treatments, and practice management. Attendees will gain insights from global leaders and learn the foundational skills needed for a successful career in this transformative field.

AMWC 2025 offers a science-driven program tailored to deliver cutting-edge techniques, innovative technologies, and academic debate across all aesthetic and anti-ageing disciplines. From injectables to body sculpting, skin rejuvenation to practice management, AMWC ensures a comprehensive learning experience for professionals at every career stage.

There’s also the chance to learn more about the latest devices and products entering the market from the hundreds of companies attending.

You can register at: www.amwcconference.com.

GLP-1: A WEIGHT LOSS REVOLUTION RESHAPING AESTHETIC MEDICINE

THE EMERGENCE OF THE GLUCAGONlike peptide one receptor agonist (GLP-1) has ignited an evolving situation in the Western world that experts suggest may hold tremendous promise in the quest for health and wellness. Physicians say that the phenomenon is legitimate, and as further study illuminates our understanding, even greater possibilities appear on the horizon 1 .

Jonathan E. Schoeff, MD, is medical director of The Longevity Lab, Aesthetics & Wellness (Greenwood Village, Colo., USA). The wellness arm of his practice employs GLP-1 drugs as a tool to achieve weight management and improve body composition as part of a total wellness plan. ‘I won’t put patients through anything I haven’t used myself, so I’ve tried every GLP-1 agent available on the market, as well as those in Phase III trials and not yet commercially available,’ he said. ‘These are powerful tools and they work.’

Many are eager to participate, some due to the exciting possibilities for patients, others driven by financial opportunities. What does this mean for practitioners?

‘GLP-1 has dramatically affected the way aesthetic practices operate and where they generate their business, as well as patient flow,’ said Erik Haines, managing director and head of Qsight (New York, N.Y., USA), a company focused on assembling and analyzing data in aesthetics, medical technology and therapeutics. ‘According to our data, within a matter of 2 years, the monthly estimated sales of weight loss treatments by aesthetic practices has ballooned from about $20 million per month to more than $160 million per month, and at least 90% of that surge is due to GLP-1 drugs,’ he stated, adding that the remainder consists of treatments and services that have been around for a while. ‘This has shuffled things around in terms of how practices market to and acquire new patients, how patient share of wallet is allocated, and in some cases defines the overall performance of aesthetic practices that choose to offer or not offer them. GLP-1 has dramatically disrupted how the industry operates in just the past few years. For example, more than 60% of medspas in the US currently offer GLP-1, and that number was virtually zero a few years ago.’

How GLP-1 works

Semaglutide, tirzepatide, liraglutide, dulaglutide and other similar compounds belong to the class of drugs known as GLP-1 agonists. They are not new and have been known primarily for their application to manage blood sugar for patients with diabetes. According to Dr Schoeff, these are analogs to glucagon-like peptide one, which upregulates the production of insulin in response to the rise in blood sugar associated with food consumption. Common side effects tend to be gastrointestinal in nature and typically manifest early in the use of the agent(s) and as peak dosages are reached, but otherwise treatment is eminently tolerable; there are more serious, but rarer, side effects.

According to our data, within a matter of 2 years, the monthly estimated sales of weight loss treatments by aesthetic practices has ballooned from about $20 million per month to more than $160 million per month, and at least 90% of that surge is due to GLP-1 drugs.

The impact of the medical use of GLP-1 for weight management on aesthetic medicine and the market is rapidly becoming apparent. Supply issues abound, pharma companies labour to maximize their stake, and the US FDA watches closely.

Erik Haines

The mechanism of action for weight loss is not as well understood but is believed to be threefold, according to Dr Schoeff. ‘First, we see a slowing of movement of food matter through the digestive system,’ Dr Schoeff continued, ‘with markedly slower emptying of the stomach, which we call delayed gastric emptying (and not “stomach paralysis”, which is a misnomer). You feel fuller more rapidly and for a longer period. Next, we have GLP-1 acting on the pancreas itself, regulating secretion of insulin at levels appropriate for, and in response to, the present level of blood sugar. Elevated blood sugar is responsible for so many things, such as heightened inflammation and connected to a growing list of resultant conditions, including diabetes, cardiovascular disease, dementia, and more. An effective agent that impacts insulin resistance

JONATHAN E. SCHOEFF, MD, Medical Director of The Longevity Lab, Aesthetics & Wellness, Greenwood Village, Colo., USA; ERIK HAINES, Managing Director and Head of Qsight (New York, N.Y., USA); STEVEN DAYAN, MD, Facial plastic surgeon, Chicago, IL USA; JOHNNY FRANCO, MD, Plastic surgeon, Austin, Tex., USA

and glucose load is incredibly important.’

‘Lastly,’ he continued, ‘and perhaps where GLP-1 is so effective, is the reduction of cravings. Some call this “food noise,” how our brains impact our desire to consume food in response to boredom, stress, etc., and it seems substantially reduced in GLP-1 users. You have gastrointestinal slowing, more appropriate insulin response, improved insulin sensitivity, and a psychological impact working together, and the overall effect is profound.’

Depending on the application, these are typically administered by subcutaneous injection on a weekly basis. However, this is not necessarily the best way to harness these drugs for weight loss, according to Dr Schoeff, and further study is necessary to determine ideal dosing strategies and other variables. ‘We’re looking hard at microdosing, for example,’ he said, ‘and Big Pharma is not happy with this. As I see it, they want to try to control how we obtain and administer GLP-1 to their financial benefit and to the detriment of clinicians and their patients, which is something to keep an eye on as it develops. Commercially available dosing pens limit options for use.’

Studies indicate that semaglutide and tirzepatide are the best for encouraging weight loss, with liraglutide and dulaglutide trailing close behind, but the situation is rapidly evolving. ‘Pharmaceutical companies are pushing through better, targeted products for weight loss,’ Dr Schoeff said, ‘so our knowledge base and the viable product range are rapidly proliferating.’

‘Aesthetic medicine has tools to help combat the side effects, such as biostimulators, fillers, muscle stimulation, and anything that helps combat laxity,’ said plastic surgeon Johnny Franco, MD (Austin, Tex., USA), who offers GLP-1 through his practice. ‘But that’s not where the story is. That, and the odd way we’ve been on the fringe but driving so many trends such as wellness and regenerative medicine, is rapidly altering the landscape.’

The evolving role of aesthetic medicine

‘The relationship between aesthetic medicine and GLP-1 for weight loss is new, complicated, and rapidly evolving. It reminds me of the rise of injectable neurotoxin for glabellar lines, when nobody understood exactly what we had in our hands,’ said facial plastic surgeon Steven Dayan, MD (Chicago, Ill., USA). ‘What I see is a healthcare revolution, with more than 40% of the US population obese and 70% obese or overweight. Millions are losing weight with GLP-1 drugs, something like more than 13% of the US population is on them or has tried them. These millions may not have been considering aesthetic medicine at first, but many are now.’

The overall impact on life globally will be much greater, Dr Dayan continued. ‘Improved weight and metabolic health, plus the rapidly unfolding laundry list of additional positive effects of GLP-1 that we’re only beginning to learn about, are poised to transform overall population health, leading to savings of billions of dollars in healthcare costs, fewer workdays lost to health issues, and greater quality of life. We’re just scratching the surface.’

We have GLP-1 acting on the pancreas itself, regulating secretion of insulin at levels appropriate for, and in response to, the present level of blood sugar. An effective agent that impacts insulin resistance and glucose load is incredibly important.

Jonathan E. Schoeff, MD

Rapid weight loss leads to skin laxity and loss of muscle mass, and aesthetic medicine has a variety of tools in the armamentarium to address both. However, there may be much more to the story, according to Dr Dayan, co-author of an article2 suggesting that the expected side effects of GLP-1 assisted weight reduction may be more prevalent than if they simply lost weight rapidly through diet and exercise. ‘This is especially true for skin laxity, and we need to take a closer look at how GLP-1s affect adipose-derived stem cells (ADSC). The data suggests that GLP-1 agonists (specifically liraglutide in the study) are capable of inhibiting in vitro proliferation and differentiation of human precursor adipose stem cells, but not mature adipocytes.’

Another study offers a contrasting viewpoint, according to Dr. Dayan. ‘A 2024 paper3 showed that 6-month semaglutide therapy modified ASDC adipogenic potential, promoting the formation of healthier, metabolically active adipocytes with increased glucose uptake. It also lowered blood glucose and induced weight loss without promoting systemic insulin sensitivity.’

To the patient, it always starts with weight loss. ‘People tend to be hyperfocused on weight loss, looking better and fitting into those old clothes,’ Dr Dayan continued, ‘but after they drop 5% to 10% of their body weight they begin to notice issues that aren’t likely to resolve themselves. They become more interested in how they look, and the laxity stands out.’ As time passes, nutritional deficiencies, especially when weight loss is not properly monitored, take their toll. ‘People may lose too much muscle mass, which has its own set of side effects, and may even begin to lose their hair.’

Dr Dayan has performed various aesthetic treatments to alleviate the untoward sequelae of GLP-1 weight loss but does not offer GLP-1 in his practice. ‘If one is to offer GLP-1 and any weight loss treatment or guidance, best practices include monitoring their blood sugars, metabolic profile, and so on as well as providing expert guidance. You can’t just sell it, and I think too many people are doing that right now.’

Offering GLP-1 in the aesthetic practice

Many see GLP-1 as a gateway to other therapies, but they should be treated with the greatest respect, according to Dr Franco. ‘I don’t go a week without outreach from a physician asking about how to integrate this into the practice.’

‘First off, we need to define “weight loss,” clinically and for patients,’ Dr Schoeff added. ‘Clinically, we mean shedding extra fat, but most people focus on scale weight, which includes loss of muscle mass due to caloric restriction. If you’re not careful, you’re losing too much muscle, which is a metabolic disaster. Disproportionate loss of lean muscle versus fat is termed “sarcopenic obesity,” and I believe we’ll see this diagnosis become exceedingly common if we, as an industry, are not fighting to preserve muscle. And it won’t be the fault of GLP-1, it’ll be our fault. Lean muscle mass is essential for an optimized metabolism, as well as our basic health and function.’

‘We offer a full spectrum of services to support offering GLP-1, and we stand out in the market,’ Dr Franco said. ‘However, one cannot simply offer this and be done with it. You need a weight loss arm of your practice, including dedicated staff and people with medical expertise to advise and monitor weight loss patients. Diagnostics are an issue because why is the person overweight? It may be disease- or medicationrelated, a thyroid problem, or any number of things beyond “you just eat too much and don’t move enough”.’

the door to other interventions in the future, especially to patients otherwise naive to aesthetic medicine.’

Another key unknown is how GLP-1 is affecting treatments which may combat issues such as laxity on the face and body, and loss of muscle mass, associated with its use. ‘The information is still mixed overall, but data suggests that in some instances we’re seeing increased spending by more affluent patients on premium treatments that deal with these side effects,’ Haines said.

‘In my eyes, the best way to get into this market is to begin by marketing yourself as being able to treat issues like laxity and muscle loss using our armamentarium,’ Dr Franco concluded. ‘As we learn just how unique this new patient population is, getting in on the ground floor like that is the safest option. There are unresolved questions surrounding the issue of GLP-1 for weight loss.’

The industry overall

The big question in the industry today, according to Haines, is how GLP-1 is affecting that ‘share of wallet’. ‘Are patients now spending on GLP-1 instead of other treatments, or is GLP-1 bringing patients who wouldn’t be there otherwise into aesthetic practices?’ Among conflicting information, there is one clear conclusion. ‘Patient spending on GLP-1 is sapping revenue from other treatments on average in the US, but these patients are also spending more money overall. This is a boon to practices offering these drugs, and intuitively, this opens

Millions are losing weight with GLP-1 drugs, something like more than 13% of the US population is on them or has tried them. These millions may not have been considering aesthetic medicine at first, but many are now.

Steven Dayan, MD

Perhaps the greatest area of uncertainty involves the availability of reliable supplies of viable GLP-1 drugs, Haines suggested.

‘Skyrocketing demand has created supply problems such that the US FDA has repeatedly put many on the shortage list, affecting how and under what circumstances these drugs can be obtained. New formulations are being developed and tested, while pharma companies are battling for the best position in the game as it unfolds. How this all plays out is anybody’s guess and will be interesting to watch.’ ‘It’s time to take responsibility as prescribers and clinicians when it comes to the appropriate use of GLP-1s,’ Dr Schoeff added. ‘Clinicians should take the lead, making sure we’re using and marketing these responsibly to maximize patient safety, confidence, and outcomes. We’re uniquely positioned to help patients navigate this successfully and we must put their wellbeing first, especially with all the hype and new developments to wade through, so that we’re on the right side of this healthcare revolution. The impact of GLP-1 on combating insulin resistance alone is going to transform modern medicine, so long as we act responsibly.’

Written by Kevin Wilson, contributing editor

PRACTICE MARKETING: THE AI EFFECT

Artificial intelligence is changing plastic surgery marketing in ways that help and could hurt a practice’s image. We delve into the potential uses of AI and explore the pitfalls

WHETHER YOU REGARD

artificial intelligence (AI) as the big bad wolf or a saviour, the reality is that AI is infiltrating everything we do, including how plastic surgeons worldwide market their practices.

Depending on how it is used, AI can help to make or break practices’ marketing campaigns.

From reactive to proactive AI has ushered a crucial shift in aesthetic practice

marketing—toward AI-powered, strategy-focused approaches, according to Christopher Suchánek, CEO at Firm Media.

AI’s ability to develop innovative, results-oriented strategies can give aesthetic practices an edge in an increasingly competitive marketplace, he said.

For starters, AI ensures that marketing strategies are not just reactive but proactive, says Mr. Suchánek, who presented ‘What’s Next In Digital Marketing and How is AI Changing the Way You Market Your Practice?’ at this year’s Aesthetic Meet conference in Austin, Texas, US.

‘AI is changing aesthetic practice marketing by excelling

One way aesthetic practices are using AI is in content creation, which includes AI-generated emails, blogs, and social media posts.

in strategy development—an often overlooked but critical component of successful campaigns,’ Mr Suchánek tells PRIME. ‘Unlike traditional tools that focus on executing tactics, AI enables practices to create data-driven, dynamic strategies tailored to their unique goals and patient demographics.’

Among the game-changers associated with AI are AIpowered tools that can analyze trends to uncover opportunities.

‘This allows practices to allocate budgets effectively, choose the right messaging, and identify the best channels for engagement,’ he says.

Content creation

One way aesthetic practices are using AI is in content creation, which includes AI-generated emails, blogs, and social media posts.

According to an American Marketing Association (AMA) survey of more than 1,000 professional marketers, AI assists marketers with writing blog posts, scripts, and articles, allowing these professionals to quickly generate ideas and drafts. About one in four marketers use generative AI for brainstorming and ideation for new campaign angles and more.

‘When it comes to design, AI tools streamline the process of creating visuals, from graphics to videos, allowing marketers to produce designs at a fraction of the cost and time,’ according to ‘Generative AI Takes Off with Marketers,’ published on AMA.org1.

AI practice marketing pitfalls

Human oversight and interaction are keys to successful

marketing campaigns using AI. In fact, experts say human involvement is paramount whether practices use AI to build ad campaigns, for search engine optimization, or write copy.

Facial plastic surgeon Corey Maas, MD, of the Maas Clinic in San Francisco, California, US, and colleagues at the California Society of Facial Plastic Surgery have analyzed AI-generated content quality and accuracy and are concerned.

Content written by doctors may have opinions, but the content is generally cited and supported with data. According to Dr Maas, AI grabs available data from all kinds of sources (not just PubMed) and sometimes generates opinionated and convincing material that is not scientifically based.

‘[AI-generated content] is written as though it is a fact, when in fact, it’s not a fact,’ he says.

Dr Maas says he writes content for his website but agrees that AI can save time by helping to create lists or outlines that help organize thoughts and offer ideas.

AI may, in the future, have some advantage—once the system is able to capture level 1 evidence, according to Dr Maas.

Amy Gwiazdowski, vice president of communications at the Chicago, Illinois-based American Marketing Association, agrees that things like ChatGPT effectively and efficiently help develop ideas and lists for blog posts and more. She also agrees that when used without human review and editing, AI-generated content can be inaccurate and backfire on any business type—especially in healthcare.

‘You see it being used for article [writing], but there needs to be a backstop. We need to make sure there is

and innovation

American Marketing Association, Chicago, IL USA

CHRIS SUCHÁNEK CEO , Firm Media, Ontario, Canada; COREY MAAS, MD, Facial plastic surgeon, Maas Clinic, San Francisco, CA, USA; AMY GWIAZDOWSKI VP, Communications, American Marketing Association, Chicago, IL USA; JEN O’BRIEN Director of research

editing involved—that people are actually looking at the tone. You don’t want to turn people off,’ Ms. Gwiazdowski says. ‘… you also need to make sure the information is accurate. AI may be pulling old information. It may not be pulling the most recent information that is behind a firewall or pay-wall.’

Using AI-generated responses in media relations might do more harm than good. For example, some people use AI to curate quotes in response to media inquiries. That’s a no-no and is unethical, according to Gwiazdowski. Doing so could destroy reporters’ and editors’ trust in expert sources because they are using AI to craft a quote they never said.

Another big AI push is the move from chatbots to agents. Consumers today are using chatbots to research procedures, prices, and provider options. In the future,

we may see consumers using autonomous agents to book appointments, manage care, and make follow-ups.

It is also important to check AI-generated content for bias. There is a lot of bias used in AI training data that may come out. And make sure the information reflects a brand’s (or practice’s) philosophy.

‘The biggest risk I see to healthcare marketers using AI is that it could possibly lead to a loss of customer trust,’ says Jen O’Brien, AMA director of research and innovation and coauthor of the article on AMA.org. ‘We don’t want to expose any personal information to any of the training data.’

Seeming fake or off-brand is another pitfall, according to Ms O’Brien, who cites the recent controversy in which Anthropologie, which is about supporting small creators and small businesses, used AI to design its bags.

‘It really did damage in terms of them not living up to their brand promise,’ Ms O’Brien says.

And AI automation (while it can save time and money) can eliminate personal touch, creating a bad customer experience. Some examples from the corporate world include when McDonald’s failed an attempt to automate

orders, and an Air Canada chatbot provided false information to travellers.

‘Marketers have to be very aware of how things can [and do] go wrong; know what those issues are and stay up on that,’ Ms O’Brien notes.

Mr Suchánek adds that a lack of understanding of AI can result in disjointed strategies, inefficient campaigns, and wasted resources.

‘Many practices focus on execution without realizing how AI can strengthen the foundation of their marketing strategy. Without AI, practices may rely on outdated assumptions or incomplete data, leading to misaligned campaigns and missed opportunities. To avoid these pitfalls, aesthetic providers should invest in understanding how AI can enhance strategy development,’ he says.

AI complements rather than replaces traditional marketing

AI complements, rather than replaces, traditional marketing tactics, according to Mr Suchánek.

‘While AI excels at developing strategies rooted in data, traditional methods like print ads, social media, and event marketing remain invaluable for building trust and fostering human connections. Together, these approaches create a cohesive, multi-channel marketing plan,’ he explains.

For example, according to Mr Suchánek, AI can identify which demographics respond best to print ads, allowing practices to refine traditional tactics.

The future

The future of AI in marketing lies in its ability to optimize both strategy and execution, according to Mr Suchánek.

‘AI will continue to refine strategic planning, offering deeper insights into market trends while automating repetitive tasks to maximize efficiency,’ he says.

While AI technology is getting better, it does not need to advance for the technology to cause future disruption in business marketing, according to Ms O’Brien.

In 2025, Ms O’Brien foresees AI video generation technology getting better and cheaper. Marketers can leverage this technology to create short-form video ads and social media content, a format ‘that consumers are hungry for and companies are investing in.’

Another big AI push is the move from chatbots to agents. Consumers today are using chatbots to research procedures, prices, and provider options. In the future, we may see consumers using autonomous agents to book appointments, manage care, and make follow-ups.

‘Now is the time to adopt AI because practices that embrace it can develop more effective marketing strategies and achieve better outcomes with less effort,” Mr Suchánek notes.

Do not forget to ask the right questions if you are working with a partner or agency, so that you can make good decisions about where and when to use AI in order to protect your brand, Ms O’Brien adds.

Written by Lisette Hilton, contributing editor

COVERSTORY

ADVANCED USE OF BIOTECHNOLOGY, RADIOFREQUENCY AND EXOSOMES FOR FACIAL REJUVENATION

Aris Sterodimas and Beatriz Nicaretta detail how the integration of advanced modalities such as stromal enriched lipograft, helium plasma RF, and exosome therapy is transforming facial rejuvenation

ARIS STERODIMAS MD, M.SC, P.HD, ARCS, Head of the Plastic & Reconstructive Surgery Department, Metropolitan General Hospital, Athens, Greece; BEATRIZ NICARETTA MD, M.SC, Deputy Head of the Plastic & Reconstructive Surgery Department, Metropolitan General Hospital, Athens, Greece

email: aris@sterodimas.com

ABSTRACT

The pursuit of facial rejuvenation has significantly evolved with the advent of advanced biotechnology, emerging technologies, and the innovative application of exosomes. This review delves into the multifaceted approaches revolutionizing aesthetic plastic surgery, focusing on minimally invasive techniques aimed at restoring youthful skin. Biotechnology advancements, including stem cell therapy, offer groundbreaking methods for enhancing cellular regeneration and repair. Emerging technologies such as helium plasma radiofrequency have refined the precision and efficacy

THE AGING OF THE FACE IS DETERMINED by a complex set of events involving skin and superficial musculoaponeurotic system (SMAS) laxity and redundancy, reabsorption of fat, and the diminution of projection on many facial prominences, as well as thinning of the dermis and decreased quality of the cutaneous draping. The outward signs of aging can be very evident in the face and neck area. Changes aﬀecting the appearance of the face and neck can include an increase or decrease of subcutaneous fat, forehead ptosis, middle face laxity, upper and lower eyelid laxity, platysmal banding, jowling, and generalized neck skin laxity. Depending on the severity, a range of treatment options is available for use alone or in combination for treating the aging face and neck1 .

Facial rejuvenation is increasingly challenging as patients expect minimally invasive procedures and rapid post-treatment recovery, along with fast, tangible, and longterm results. Rejuvenation of the

of aesthetic treatments. Central to these advancements is the utilization of exosomes—nano-sized extracellular vesicles derived from stem cells— that play a pivotal role in cell communication and regeneration. This paper looks at current research and clinical practices, highlighting the synergistic effects of combining these innovative approaches for optimal facial rejuvenation. The integration of these technologies signifies a paradigm shift towards more effective, personalized, and less invasive aesthetic treatments, offering promising avenues for future research and application in cosmetic surgery.

face frequently requires surgery on multiple areas, in addition to the increasing number of procedures involving face sculpturing and biostimulation through fat injection. At our institution, we employ a systematic approach that uses all of these procedures with consistent results. Although the gold standard continues to involve the traditional facelifting surgical procedure, there is a continuous shift toward minimally invasive techniques2,3. Our research group has already described the method of stromal enriched lipograft (SEL) for the face and various parts of the body; a procedure combining fat with enzymebased extraction of the stromal vascular fraction (SVF), with the aim to increase the take and duration of the grafted fat and the related volume, thereby determining a more predictable and stable result in terms of graft survival4,5

Facial rejuvenation is increasingly challenging as patients expect minimally invasive procedures and rapid post-treatment recovery, along with fast, tangible, and long-term results.

Several technologies, including laser, ultrasound, and radiofrequency (RF), have demonstrated some skin tightening. The mechanisms of action for subcutaneous RF devices include the generation of heat through tissue resistance within the dermis and fat that

results in neo-collagenesis, elastin and dermal matrix remodeling, and mild adipocyte loss. The contraction of the subcutaneous tissue by deeper application of helium plasma RF technology is felt to be an additional mechanism that results in additional skin contouring by soft-tissue contraction. The reduction in volume and tissue surface area is the result of protein denaturation and collagen contraction after a thermal energy threshold has been transmitted to the tissue. Recently, a plasma-driven RF device, Renuvion (Apyx Medical, Clearwater, FL), was introduced, and the Food and Drug Administration (FDA) cleared this device as the only device for soft-tissue coagulation and skin contraction. The Renuvion system for the face and neck utilizes cold helium plasma via a gas ionization process to produce a stable, focused beam of energy that results in tissue contraction which reaches the maximum effect at 6-9 months after the application6

Exosomes can modulate essential cellular processes, such as proliferation, differentiation, migration, and cell death, depending on the exosome origin, the physiological and pathological state, and even the precise cellular release site.

membranes and carry important gene information, such as proteins, carbohydrates, lipids, and nucleic acids. Exosomes possess the capacity to function as intercellular transmitters to impact neighboring cells while retaining some of the biological properties of their parent cells2.

Indications for the procedures

The epidermal, dermal, and subcutaneous tissue thickness and the degree of bone recession in the glabella and along the supraorbital rims are documented when analyzing the upper third of the face. The degree of photodamage can also be recorded. Deeper rhytids can be noted for possible sharp-needle intradermal fat grafting (SNIF) technique. Temporal depression is associated with deep fat loss, whereas increased show of the temporal veins is associated with superficial fat loss. Often, both are present in middle-aged men and women.

The upper and lower eyelids and periorbital region are inspected. Loss of fullness of the lateral brow, loss of convexity of the skin caudal to the eyebrow, and supratarsal fold depth can be noted. In the inferior orbit, the rim is evaluated, as is the prominence of the intraorbital fat. The tear trough and lid cheek junction must also be evaluated. The position of the globe is noted from the vertex view to determine the degree of proptosis. The lid to pupil position is noted and the degree of senile enophthalmos is evaluated.

In the middle third, the zygomatic arch and body are outlined. The superior arch corresponds with the inferior temporal region. The deep lateral and medial suborbicularis occuli fat (SOOF) are noted, as is the deep medial fat compartment of the cheek. The degree of buccal hollowing is evaluated. The nose is assessed for any aesthetic deformity and/or aging and the degree of pyriform recession is noted. The lips, perioral tissues, and degree of thinning and rhytids are evaluated.

In the lower third, the marionette basin is evaluated as the chin and labiomental fold. Chin texture may be improved with nanofat microneedling. The prejowl area just lateral to the mandibular retaining ligaments, if scalloped, is addressed as is the inferior border of the mandible and the gonial angle. Chin projection is evaluated, and the neck is inspected for fat excess or degree of subcutaneous loss, deep and fine rhytids and severity of laxity. The skin laxity in the forehead, lower eyelid and neck area are evaluated, and the Renuvion helium-based RF technology can be indicated along with the stromal enriched lipograft technique. Exosomes can modulate essential cellular processes, such as proliferation, differentiation, migration, and cell death, depending on the exosome origin, the physiological and pathological state, and even the precise cellular release site.

Markings and surgical technique

Exosomes are cell-derived nanoscale vesicles with a diameter of 40–160 nm. They are structures with bilayer

Areas to be treated are typically marked with a point in a topographic pattern. Zones of adherence and areas to avoid are marked with hash marks. Grid markings are made in order to standardize resection and reduce contour irregularities. Incisions should be placed in natural creases to minimize visibility. It is important to

review all markings and access incision locations with patients in front of a mirror before performing the surgical procedure.

Markings for Renuvion treatment on the forehead, face, and neck are made while the patient is standing. The procedure, performed under sedation and local anesthesia in the supine position, includes intraoperative intravenous cefazolin. Local anesthetic comprises a saline solution with 1:100,000 adrenaline and 50 ml of 2% xylocaine, injected using a 23G cannula. After 15 minutes, a 2 mm blunt cannula is used to access the forehead area via three incisions behind the hairline. At the supraperiosteal level, the Renuvion 15 mm probe is employed to achieve skin contraction through helium plasma radiofrequency (RF) technology. The target subcutaneous temperature (75–85°C) is maintained for over 120 seconds to ensure optimal contraction. Using a 65% energy setting and 1 liter of helium plasma flow, the device is operated in a retrograde manner with a maximum of five strokes per 2 cm. Helium gas is released through three incision sites and manually expelled or suctioned to prevent subcutaneous emphysema.

For lower eyelid treatment, 15 ml of local anesthetic is injected per side through a precapillary temporal incision. After subcutaneous undermining with a 23 G cannula, three stab incisions are made. The Renuvion 15mm probe, set at 65% energy and 1 liter of helium plasma flow, treats the subcutaneous level of the lower eyelid. The device is moved retrograde, with no more than three strokes per 1 cm, ensuring precision and safety.

When liposuction of the neck is required, the authors inject a saline-wetting solution containing 1:200,000 of adrenaline and 50 ml of xylocaine 2% via a small-bore 21 G cannula into the neck’s subcutaneous tissue. After waiting 15 minutes, a 20 mL syringe attached to a 2mm blunt cannula is inserted through small incisions in the postauricular crease. Fat is aspirated with a 2 mm four-hole aspiration blunt-tip cannula connected to a 20 mL LuerLok syringe. The distal openings of the harvesting cannula are of an appropriate size and shape for harvesting the largest intact fatty tissue parcels that can readily pass through the lumen of a Luer-Lok syringe. The combination of slight negative pressure and the curetting action of the cannula’s motion through the tissues allows parcels of fatty tissue to move through the cannula, through the Luer-Lok aperture, and into the barrel of the syringe with minimal mechanical damage. When liposuction is complete, the specific Renuvion 15 mm probe for the neck region is used. The energy is set to 75%, and a helium plasma flow of 1.5 liter is recommended when treating the neck area. Once engaged, the device is drawn backwards from the end of the treatment area toward the entry site. No more than six strokes are performed for every 1.5 cm. Again, the device is disengaged 1 cm from the entry site to prevent incision burns, and the helium gas needs at least three stab incision sites to have adequate space to escape.

The adipose tissue aspirated by liposuction is processed in the following manner, as previously described in the medical literature by our group7. First, two-thirds of the aspirated fat is used to isolate the SVF. Digestion is obtained with 0.075% collagenase type II GMP grade (ClZyme AS),

Figure 1 Stromal enriched lipografts assigned to anatomic locations according to their sizes: millifat, microfat, and nanofat

Type of fat grafts

Bone onlay grafts

Ligamental support grafts

Fat-lifting

Deep fat compartments

Superficial fat compartments

Subdermal

Intradermal (SNIFF)

Mesotherapy

Microneedling

Topical

Millifat (2.4 mm<) injections Microfat (1.2 mm<) injections Nanofat (400-600<) injections

• Ligamental lifting

• Periperiosteal full face

• Zygomatic arch, mandibular arch, bone onlay

• Ligamental

• Mid-face, pre-zygomatic pre-maxillary deep fat pads

• Sub-orbicularis oculi fat

• Buccal fat space

• Forehead

• Peri-oral

• Chin

• Deep tear trough

• Hands

• Superficial fat replacement

• Intradermal injections

• Peri-oral and peri-orbital mesotherapy

• Topical delivery

produced by VitaCyte LLC (Indianapolis, IN) in buﬀered saline, and agitation for 45 minutes at 37°C is performed.

Separation of the SVF containing adipose-derived stem cells (ADSCs) is then accomplished by using centrifugation at 1,200 rpm for 5 minutes, according to the protocol already published. The SVF is located in the pellet derived

A A B B B

from the centrifuged fat at the bottom of the lipoaspirate. The SVF is derived from the fat processed in an automated cell processing unit.

The remaining one-third of the aspirated fat is treated in the following way: with the syringe held vertically with the open end down, the fat and fluid are separated. Isotonic saline is added to the syringe, the fat and saline are separated, and the exudate is discarded. The procedure is repeated until the fat becomes yellow in color, free of blood and other contaminants, purified, and concentrated; therefore, it is treated as delicately as possible to maintain an intact architecture. The process only involves washing and gravity separation. SVF containing ADSCS and the purified fat are finally mixed and transferred into 20 mL syringes. Each syringe contains 1.5 mL of SVF and 18.5 mL of purified fat. This portion of prepared millifat is set to the side to replenish deep fat compartment loss and facial bone recession. The remaining 40 ml of millifat is transferred into two 20 mL syringes and processed into microfat and nanofat using the Nanocube kit, which has 4 ports that resize fat using a special cutting technique. The adipose tissue graft enriched with SVF is injected through the incisions and delivered as milli, micro and nano fat. The lipograft is injected at various levels of depth, from the subcutaneous–dermal junction down to the deep subcutaneous fat, until the desired projection is obtained. The fat is introduced as the cannula is withdrawn. Fat molding is performed by gentle digital manipulation to achieve a uniform distribution. Placement starts with the deep compartments of the face and progresses superficially, using millifat first, then microfat, and ending with nanofat. Up to 5 puncture sites per side are made with an 18 G needle and are reused whenever possible in delivering the 3 sizes of fat grafts (Figure 1). According to the topographic assessment, fat grafts are assigned to anatomic locations in the face according to their parcel sizes of millifat (2–2.5 mm), microfat (1 mm), and nanofat (500 µm and less).

Postoperative care

Postoperative care consists of analgesia, nonsteroidal anti-inflammatory medications, and arnica for bruising. Direct application of ice is not permitted. Patients can expect facial swelling and mild ecchymosis, which generally dissipate by day 5–7. Immediate postoperative dressing was applied to the lipoaspirated area of the neck. Patients who have undergone the combination of the SEL technique and the Renuvion technology as a part of the innovative minimal invasive protocol for face contouring and rejuvenation have experienced a significant decrease and reversal of tissue decay. The combination of emerging technologies and adipose-derived stem cell fat grafting has proved in the laboratory through animal studies that may boost the regenerative effect of helium plasma on upregulating the number and the survival of adipose stem cells6. As a result, the fat graft survival of the transplanted fat using the SEL technique combined with Renuvion may play a significant role in reversing the signs of aging. Complications from the combination of SEL and Renuvion have been rare and only related to excessive fat grafting and minor burns when the physician is not following the recommended protocol.

Figure 2 A 47-year-old woman requesting facial and neck contouring and rejuvenation. A) Before and (B) after stromal enriched lipograft technique assisted by the helium plasma-based technology as an innovative, minimally invasive approach for face contouring and rejuvenation

Figure 3 A 44-year-old woman requesting facial and neck contouring and rejuvenation. A) Before and (B) after stromal enriched lipograft technique assisted by the helium plasma-based technology as an innovative, minimally invasive approach for face contouring and rejuvenation.

Figure 4 A 62-year-old man requesting facial and neck contouring and rejuvenation. A) Before and (B) after undergoing stromal enriched lipograft technique assisted by the helium plasma-based technology as an innovative, minimally invasive approach for face contouring & rejuvenation.

Case demonstrations

Case 1

A 47-year-old woman requested face and neck contouring and rejuvenation (Figure 2A). She underwent forehead, lower eyelid and neck treatment using the Renuvion technology. A total of 38 mL of SEL fat (milli, micro and nano) was placed in the temporal area, brows, cheeks, tear trough, nose, nasolabial folds, lips, and marionette lines. Exosome application using RF microneedling was used, too. Her appearance after 2 years of treatment is shown in Figure 2B

Case 3

A 44-year-old woman requested contouring and rejuvenation for her face and neck (see Figure 3A). She underwent treatment of the forehead, lower eyelids, and neck using Renuvion technology. A total of 29 mL of SEL fat (in milli, micro, and nano sizes) was injected into the temporal area, brows, cheeks, tear troughs, nose, nasolabial folds, lips, and marionette lines. Additionally, exosome application was performed using RF microneedling. Her appearance 3 years after the treatment is shown in Figure 3B.

Case 4

A 62-year-old man requested face and neck contouring and rejuvenation (Figure 4A underwent forehead treatment, lower eyelid and neck treatment using the Renuvion technology. A total of 32 mL of SEL fat (milli, micro and nano) was placed in the temporal area, brows, cheeks, tear trough, nose, nasolabial folds, lips, and marionette lines. Exosome application using RF microneedling was used, too. His appearance after 2 years of treatment is shown (Figure 4B).

Discussion

autologous ADSCs offer the possibility of finally fulfilling the key principle of replacing like with like as an aesthetic filler9. ADSCs are multipotent mesenchymal stem cells that display a regenerative capacity by the paracrine release of growth and differentiation factors. ADSCs are responsible for the rejuvenation capabilities of fat grafts, and their use has shown a lower reabsorption rate due to improved angiogenesis and reduced inflammatory response. In SEL, ADSCs are used in combination with lipo injection10. An SVF containing ADSCs is freshly isolated from the aspirated fat and recombined with the adipose scaffold. This process converts relatively ADSC-poor aspirated fat to ADSC-rich fat. ADSCs remain the most widely used by cosmetic surgeons as they have the potential and capability to differentiate into mesenchymal, ectodermal, and endodermal lineages and are easily accessible to harvest. The regenerative effects of ADSCs on facial aesthetics have been shown at the histologic and cellular level11.

Facial aging presents a challenging problem for plastic and aesthetic surgeons; it is a multifactorial, multistep process that involves structural and volumetric changes in the skin, muscles, skeleton, and adipose tissue. Facial tissue descent is caused not only by gravity but also by reabsorption and repositioning of the facial adipose system. Facial rejuvenation with autologous fat has the advantage of replacing or augmenting tissue with equivalent tissue8. Autologous fat transplantation to the face can correct cosmetic defects that are caused by loss of subcutaneous tissue, such as atrophy of the face due to significant weight loss, wrinkles, and facial involution due to aging. Clinical use of autologous fat grafts for facial soft-tissue augmentation has grown in popularity in the plastic surgery community in the past 10 years.

Regenerative cell-based strategies, such as those encompassing the use of stem cells, have shown that

With each stroke of the Renuvion device, the RF energy encounters tissue with varying impedance and will continuously change paths of heat transfer. There is minimal depth of thermal eﬀect and prevention of overtreating tissue even with multiple passes while maximizing treatment of untreated tissue.

The helium-based RF technology into the forehead, lower eyelid and neck areas for a brief interval results in precise, predictable effects on the skin and underlying connective tissue. Rapid heating of the subcutaneous tissue and subsequent skin tightening occurs as the plasma rapidly gives up energy to the surrounding tissue with each pass of the device. With each stroke of the Renuvion device, the RF energy encounters tissue with varying impedance and will continuously change paths of heat transfer. There is minimal depth of thermal effect and prevention of overtreating tissue even with multiple passes while maximizing treatment of untreated tissue. The release of helium gas in the subdermal tissue helps rapidly dissipate the accumulated thermal energy. Because the device rapidly heats a small segment of subcutaneous collagen to 85°C, strong immediate contraction is generated within 0.044 seconds. Results can continue to improve over a year, as infiltration of new collagen within the adipose stroma occurs. Although these devices have proven effective in achieving soft-tissue contraction, the process of heating and maintaining that temperature for extended periods can be timeconsuming. In devices without an external temperature monitor, the skin surface can become overheated, causing occasional blisters or burns. One of the main challenges associated with percutaneous delivery of energy for the purpose of thermal-induced collagen tissue contraction is the balance that must be achieved between heating the internal tissues enough to achieve the desired contraction while maintaining safe external tissue temperatures. Patients unsuitable for Renuvion treatments include those with open sores, poorly controlled diabetes, autoimmune diseases, or severe neck laxity15. The combination of SEL and exosomes, assisted by helium plasma technology, ensures effective contouring and regeneration, with a high success rate and lasting results.

These approaches are also useful adjuncts to surgical treatment of more extreme degrees of skin laxity, suggesting that the future of facial and neck rejuvenation will be a palette of choices and combinations.

The exosome application in the skin contributes to the intercellular communication necessary to maintain cellular function and tissue homeostasis16. Studies have shown that the endogenic exosomes in multiple types of skin cells contributed to the complex molecular mechanisms of chronic inflammatory skin diseases17. Therefore, the exosome contents can be potential biomarkers for treating skin dysfunction and diseases. More importantly, the exosomes from stem cells and other cell types can be therapeutic options in regenerative medicine and aesthetics, especially in scar prevention and reduction, pigmentation regulation, and hair growth18. Exosomes secreted by melanocytes could regulate skin pigmentation, and exosomes originating from other cell types residing in the skin can also influence melanin production in melanocytes19. Exosomes derived from MSCs have also been classified as potentially useful as a topical treatment with no adverse effects. They have also demonstrated the potential of exosomes as therapeutic agents, cosmetic ingredients, and biological agents20 Although the desirable outcome is to produce the requested augmentation and cutaneous biostimulation of the facial region by autologous fat grafting and exosome application in one treatment, the patient should be advised that a secondary procedure may be needed to accomplish the desired result. The combination of SEL and exosomes assisted by helium plasma-based technology for the face and neck contouring and regeneration is safe and eﬀective, and the prolonged duration of the grafted fat is such that repeat procedures are rare, and this may be attributable to a more stable inhabitation of the recipient site thanks to the SEL technique.

Conclusions

This article describes a novel and highly personalized approach to using emerging technologies, like Renuvion, exosomes and fat grafting of the face and neck to address the vexatious issue of fat graft volume loss and skin laxity. The SEL method is a dynamic, anatomy-based approach to address patterns of facial aging, which occurs in specific

References

1. Sterodimas A, Nicaretta B, Boriani F. Composite Face Lifting: The Combination of Stromal Enriched Lipograft With Face Minilift and Upper and Lower Blepharoplasty: A Review of 210 Cases. Ann Plast Surg. 2020 Dec;85(6):e20-e23

2. Sterodimas A. Aging Face: The Role of Stromal Enriched Lipograft™ in Facial Rejuvenation. Clin Surg. 2019; 4: 2337.

3. Gentile RD. Renuvion/J-plasma for subdermal skin tightening facial contouring and skin rejuvenation of the face and neck. Facial Plast Surg Clin North Am. 2019; 27(3):273–290

4. Sterodimas A, Boriani F, Magarakis E, Nicaretta B, Pereira LH, Illouz YG. Thirtyfour years of liposuction: past, present and future. Eur Rev Med Pharmacol Sci. 2012; 16(3):393–406

5. Sterodimas A, de Faria J, Nicaretta B, Papadopoulos O, Papalambros E, Illouz YG. Cell-assisted lipotransfer. Aesthet Surg J. 2010; 30(1):78–81

6. Ruff P 4th, Sterodimas A Enhanced Fat Graft Viability and Remodeling Using a Helium-based Radiofrequency Device to Prepare the Recipient Site.Aesthetic Plast Surg. 2023 Dec 14.

Key points

Combining Renuvion, exosomes, and SEL-based fat grafting offers a dynamic and personalized solution for volume restoration, skin tightening, and improved surface quality.

Innovations such as helium plasma radiofrequency and stem cell-derived exosomes enhance precision and efficacy, setting new standards for minimally invasive facial rejuvenation

The SEL method targets specific fat compartments, addressing unique patterns of facial aging while offering adjunctive benefits to surgical procedures for severe skin laxity

doi: 10.1007/s00266-023-03749-6. Online ahead of print. PMID: 38097690

7. Sterodimas A, de Faria J, Nicaretta B, Boriani F.

Autologous fat transplantation versus adipose-derived stem cell-enriched li-pografts: a study. Aesthet Surg J. 2011; 31(6):682–693

8. Sterodimas A, de Faria J, Nicaretta B, Boriani F.

Autologous fat transplantation versus adipose-derived stem cell-enriched li-pografts: a study. Aesthet Surg J. 2011; 31(6):682–693

9. Sterodimas A, de Faria J, Nicaretta B, Pitanguy I. Tissue engineering with adipose-derived stem cells (ADSCs): current and future applications. J Plast Reconstr Aesthet Surg. 2010; 63(11):1886–1892

10. Sterodimas A, Boriani F, Nicaretta B, Pereira LH. Hand rejuvenation by stromal enriched lipograft. J Plast Reconstr Aesthet Surg. 2018; 71(10):1507–1517

11. Sterodimas A. Adipose stem cell engineering: clinical applications in plastic and reconstructive surgery. In: Illouz

superficial and deep fat compartments of the face and neck. In keeping with current trends of minimally invasive surgical rejuvenation of the face and neck, the authors stress the importance of combinations of techniques and modalities in order to achieve multiple goals: volume replenishment, skin tightening, and improvement in skin surface quality. These approaches are also useful adjuncts to surgical treatment of more extreme degrees of skin laxity, suggesting that the future of facial and neck rejuvenation will be a palette of choices and combinations. For patients with degrees of facial atrophy and skin laxity—a common finding—filling areas of deficiency with reliable fat cell additives has become the primary treatment. As always, it is the experienced practitioner who understands all of the available options—both surgical and minimally invasive—who is best able to meet the often-complex needs of this group of patients.

Declaration of interest The authors of this manuscript have no conflicts of interest to disclose.

YG, Sterodimas A, eds. Adipose Stem Cells and Regenerative Medi-cine. Berlin: Springer-Verlag; 2011:165–179

12. Sterodimas A. The role of stem cells in face contouring. In: Theodorou S, Chia C, eds. Liposuction & Emerging Technologies in Body Contouring. New York, NY: Thieme; 2018

13. Tiryaki T, Cohen SR, Canikyan Turkay S, Kocak P, Sterodimas A, Schlaudraff KU, Akgün Demir I, Agovino A, Kul Y Hybrid Stromal Vascular Fraction (Hybrid-SVF): A New Paradigm in Mechanical Regenerative Cell Processing. Plast Reconstr Surg Glob Open. 2022 Dec 30;10(12):e4702

14. Kølle ST, Duscher D, Taudorf M, Fischer-Nielsen A, Sterodimas Contemplations on Recent Clinical Reports on Fat Grafts Enriched With Adipose Tissue-Derived Stromal Cells. Aesthet Surg J. 2023 Mar 15;43(4):NP300-NP301.

15. Ruff PG, Bharti G, Hunstad J, Kortesis B, DiBernardo B, Gentile R, Cohen S, Martinez A, Shridharani SM. Safety and Efficacy of Renuvion Helium Plasma to Improve the Appearance of Loose Skin in the Neck and Submental Region. Aesthet Surg J. 2023 Sep 14;43(10):1174-1188

16. L. Yin, X. Liu, Y. Shi, D.K.W. Ocansey, Y. Hu, X. Li, C. Zhang, W. Xu, H. Qian Therapeutic advances of stem cell-derived extracellular vesicles in regenerative medicine Cells, 9 (2020), Article 707,10-390

17. S. Gurunathan, M.-H. Kang, M. Jeyaraj, M. Qasim, J.-H. Kim Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes Cells, 8 (2019), Article 307, 10.3390

18. Ku YC, Omer Sulaiman H, Anderson SR, Abtahi AR. The Potential Role of Exosomes in Aesthetic Plastic Surgery: A Review of Current Literature. Plast Reconstr Surg Glob Open. 2023 Jun 12;11(6):e5051

19. Stahl PD, Raposo G. Extracellular Vesicles: Exosomes and Microvesicles, Integrators of Homeostasis. Physiology (Bethesda). 2019 May 1;34(3):169-177

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NAMICA technology threads are coated with nano and microparticles of non-crosslinked HA securely embedded within a P(LA/CL) shell. This unique design allows for the gradual release of HA in the skin, ensuring prolonged hydration and biostimulation, which further enhances skin elasticity and overall quality.

ENHANCED FACIAL REJUVENATION WITH POLY(L-LACTIDE-CO-ε-CAPROLACTONE)HYALURONIC ACID THREADS

George Sulamanidze, MD, and Igor Gulyaev, MD, describe the results from their 6-month split-face study on the effects of the fourth-generation of Aptos threads

ABSTRACT

Thread lifting has gained significant attention as a minimally invasive method for facial rejuvenation, offering mechanical support alongside biostimulatory effects. Aptos has introduced advanced poly(L-lactide-coε -caprolactone)-hyaluronic acid threads with innovative NAMICA technology, enriched with non-crosslinked hyaluronic acid to deliver superior skin hydration and boost collagen stimulation.

Objective

This study aimed to evaluate the safety and effectiveness of hyaluronic acid-enriched P(LA/CL) threads (P(LA/ CL)+HA threads) with NAMICA technology, also known as Excellence Visage with hyaluronic acid (EVHA) with NAMICA technology, in facial rejuvenation compared to the previous generation of P(LA/ CL)+HA (EVHA) threads by assessing the lifting effect, improvement in skin quality and wrinkle severity.

Methods

A total of 25 patients were enrolled in two clinical sites in Tbilisi, Georgia, and Moscow, Russia. Subjects were treated using a splitface design: P(LA/CL)+HA threads (EVHA) were inserted into one face side, and the P(LA/CL)+HA threads with NAMICA technology (EVHA with NAMICA technology) were inserted into the other face side, targeting the midface and the lower face. Assessments were performed at baseline and 1, 3, and 6 months post-treatment using the

Modified Fitzpatrick Wrinkle Scale (MFWS) for wrinkle severity, the Global Aesthetic Improvement Scale (GAIS) for both physician and patient, and the QuantifiCare 3D LifeViz® Mini imaging system for objective measurement of lifting effect and skin quality parameters. Safety was monitored for up to 3 months after the implantation to address side effects and overall health.

Results

P(LA/CL)+HA with NAMICA technology threads (EVHA with NAMICA technology) and the previous-generation P(LA/CL)+HA threads (EVHA) demonstrated a similarly strong lifting effect. At the same time, the study showed a significantly stronger improvement in skin quality with NAMICA threads compared to the previous generation of P(LA/CL)+HA threads. These benefits were consistently maintained over six months, finally resulting in overall superior lifting results, as confirmed by GAIS for the physician. Both treatments were safe, with side effects being expected and mild to moderate in severity.

Conclusion

This study highlights the significant advantages of the new generation of P(LA/ CL)+HA threads with NAMICA technology over previous P(LA/CL)+HA threads in skin quality improvement along with a strong lifting effect and favourable safety profile with a reduced recovery period.

IN THE EVOLVING LANDSCAPE OF AESTHETIC MEDICINE, patient expectations have shifted toward treatments that provide multiple benefits in a single procedure. Modern aesthetic interventions aim not only to restore volume and lift sagging tissue but also to improve skin quality, texture, and elasticity. This trend has given rise to technologies that integrate lifting and biorevitalization effects, addressing various age-related changes simultaneously.

Several modalities offer lifting results in aesthetic practice. Dermal fillers, such as hyaluronic acid (HA), achieve their volumization effect through the hydrophilic nature of HA, which allows it to attract and retain water, thereby increasing tissue volume at the site of injection. However, their primary action focuses on volumization rather than mechanical lifting1-3. Neuromodulators, like botulinum toxin, reduce muscle hyperactivity to soften wrinkles and provide a subtle lifting appearance, yet they do not address tissue laxity or collagen loss4,5.

Energy-based devices, including ultrasound and radiofrequency, stimulate collagen production, promoting skin tightening over time, though results are often gradual and less dramatic6-8

Barbed threads have emerged as a particularly effective solution for mechanical lifting. These threads feature microscopic barbs that anchor into the dermal and subdermal layers, enabling the physical repositioning of sagging tissues9. In addition to the immediate mechanical effect, barbed threads induce a controlled inflammatory response, stimulating neocollagenesis and improving long-term skin firmness and elasticity10,11. This dual mechanism of action mechanical lifting and collagen stimulation makes barbed threads a cornerstone of minimally invasive facial rejuvenation.

Aptos developed the third generation of absorbable lifting threads, Visage Excellence Method HA (EVHA), poly(L-lactide-co-εcaprolactone) threads combined with non-crosslinked HA12. While crosslinked HA has been widely used in dermal fillers for its durability, non-crosslinked HA offers distinct advantages in thread applications, being more biologically active and providing better hydration, enhanced biostimulation, and reduced risk of complications associated with chemical stabilization13,14.

In recent years, Aptos advanced the technology of hyaluronic acid coating for P(LA/CL) threads, introducing NAMICA, which led to the development of a new, fourth generation of Aptos threads P(LA/ CL)+HA threads with NAMICA technology. NAMICA technology

GEORGE SULAMANIDZE, MD, Clinic of Plastic and Aesthetic Surgery and Cosmetology ‘Total Charm Orbeliani,’ Tbilisi, Georgia; IGOR GULYAEV, MD, Clinic of Plastic and Aesthetic Surgery and Cosmetology ‘Total Charm,’ Moscow, Russia email: aptos@aptos.ge

KEYWORDS Aptos threads, Barbed threads, Visage Excellence Method, Facial rejuvenation, Poly-L-lactide-co- εcaprolactone, NAMICA technology

threads, particularly the Visage Excellence Method HA (EVHA), represent a significant advancement in thread lifting. NAMICA technology threads are coated with nano and microparticles of non-crosslinked HA securely embedded within a P(LA/CL) shell. This unique design allows for the gradual release of HA in the skin, ensuring prolonged hydration and biostimulation, which further enhances skin elasticity and overall quality15. Combined with the barbed structure that provides immediate

Table 1 Percentage of subjects with improvement in Modified Fitzpatrick Wrinkle Scale (MFWS)

MFWS score improvement from baseline 1 month 3 months 6 Months

0.5 points

Assessed separately on the face side treated with NAMICA threads and face side treated with third generation HA threads (N=25)

Table 2 GAIS assessment by patient and by physician

Timepoint Score

1 – Very much improved 8 (32%) 8 (32%) 12 (48%) 15 (60%)

1 month

2 – Much improved 13 (52%)

4 – No change 0 (0%) 0 (0%) 0 (0%) 0 (0%) 5 – Worse 0 (0%) 0 (0%)

6 months 1

Number and percentage of subjects

mechanical lifting, NAMICA technology threads deliver a dual effect: physical repositioning of tissues and long-term improvement in skin texture, elasticity, and pore minimization through collagen stimulation9-17

This study aimed to evaluate the effectiveness and safety of the fourth generation P(LA/CL)+HA threads with NAMICA technology in comparison to the third generation P(LA/CL)+HA threads, specifically, the lifting effect, improvement in skin quality and recovery time after thread implantation.

Materials and methods

Patient selection

The study included adult male and female subjects with moderate to severe facial skin laxity confirmed by assessment with the Facial Laxity Rating Scale (FLRS) and wrinkle severity class 1–2.5 as per the Modified Fitzpatrick Wrinkle Scale (MFWS). Subjects agreed to have no additional cosmetic procedures during the study that might interfere with evaluation in the current study. Patients with chronic disease exacerbations, skin infection diseases, hemophilia, and malignancies, as well as pregnant or breastfeeding women, were not included in the study.

Procedure

The study utilized two models of 190 mm Aptos P(LA/CL) barbed monofilament threads different only in HA coating: third-generation EVHA with ‘plain’ HA coating or fourth-generation EVHA with NAMICA technology. Lifting was performed in the midface and the lower face. In each subject, NAMICA technology threads (1 package, 10 threads) were inserted into one face side, and thirdgeneration EVHA threads (1 package, 10 threads) were inserted into the other side. After disinfecting the treatment zones (midface, lower face, and neck), local anesthesia was administered at the entry points. A puncture site was made using an 18 G lancet needle, and threads were inserted subdermally with 20 G x 150 mm round-tip needles. After insertion, needles were removed, light pressure was applied to minimize bruising, and patients were advised to avoid facial strain for one week.

Evaluation and statistical analysis

The Modified Fitzpatrick Wrinkle Scale (MFWS) was used to evaluate wrinkle severity, categorizing wrinkles into distinct classes from no wrinkles to deep wrinkles, allowing for detailed assessment18:

■ Class 0: No wrinkle. No visible wrinkle; continuous skin line

■ Class 0.5: Very shallow yet visible wrinkle

■ Class 1: Fine wrinkle. There are visible wrinkles and slight indentations

■ Class 1.5: Visible wrinkle and clear indentation, <1 mm wrinkle depth

■ Class 2: Moderate wrinkle. Clearly visible wrinkle, 1–2 mm wrinkle depth

■ Class 2.5: Prominent and visible wrinkle. More than 2 mm and less than 3 mm wrinkle depth

■ Class 3: Deep wrinkle. Deep and furrow wrinkle; more than 3 mm wrinkle depth.

The Global Aesthetic Improvement Scale (GAIS) was used to collect an assessment of the overall aesthetic outcome from both patients and physicians. GAIS evaluates improvements in appearance compared to the pre-treatment baseline using a five-point scale19:

■ 1: very much improved

■ 2: much improved

■ 3: improved

■ 4: no change

■ 5: worsened.

To objectively evaluate the lifting effect and skin quality parameters, including wrinkles, pores, and skin evenness, the QuantifiCare 3D LifeViz® Mini imaging system was used, providing standardized and reproducible measurements.

All assessments, including MFWS, GAIS, and QuantifiCare 3D measurements, were performed at baseline, 1, 3, and 6 months posttreatment. Safety was evaluated up to 3 months after thread implantation and included an assessment of adverse events, thus addressing the treatment safety profile and the subject’s overall health during the recovery period. The Wilcoxon signed-rank and Friedman tests were used for statistical analysis within split-face and timepoint comparisons, respectively.

Results

A total of 25 patients were enrolled in this study conducted at two clinical sites between March 2023 and October 2023: 12 patients in Tbilisi, Georgia and 13 patients in Moscow, Russia. All study subjects were women aged 35 to 64 years. The mean age was 47.1 ± 8.6 years.

Wrinkle severity

as ‘worse’ or ‘no change’. Overall, the subjects’ GAIS assessments were similar for the two face sides (Table 2). GAIS for physicians also demonstrated high satisfaction with both face sides at all time the effect for most patients was assessed as ‘very much improved’ (at 1 month) or ‘much improved’ (3 and 6 months), none of the doctors assessed the effect as ‘worse’ or ‘no change’. Overall, GAIS for physician scores were similar for the two face sides, with a trend for a higher percentage of doctors assigning the best GAIS score ‘very much improved’ to the NAMICA-treated face side, compared to the third generation EVHA threads. The trend showing a greater proportion of subjects receiving the maximum GAIS score from the doctor for the NAMICA-treated side of the face became statistically significant at the 6-month mark (p=0.048, Fisher’s Exact test).

These results highlight the high and sustained performance of HA-enriched P(LA/CL) lifting threads with NAMICA technology achieving greater physician-reported satisfaction over time.

A total of 25 patients were enrolled in this study conducted at two clinical sites between March 2023 and October 2023: 12 patients in Tbilisi, Georgia and 13 patients in Moscow, Russia.

Wrinkle severity, assessed with the MFWS, demonstrated strong improvement on both sides of the face. The 1-point improvement in MFWS was the most frequent – it was observed 3 and 6 months after treatment in more than half of patients on the NAMICA-treated side and the side treated with the third-generation thread. Stronger improvement (by 1.5 points and 2 scores) was, in general, less frequent. Three months after treatment it was observed in 32% of subjects on the NAMICA-treated face side and in 20% of cases on the side treated with the thirdgeneration threads. Six months after treatment, these were 36% and 16%, respectively (Table 1).

Global Aesthetic Improvement Scale

GAIS assessment was performed separately for the two face sides and separately by the patient and the doctor. GAIS for patients demonstrated high patient satisfaction with both face sides at all time points most of the subjects assessed the effect as ‘much improved,’ and none of the subjects at any of the time points assessed the effect

Lifting effect

The lifting effect was measured using the QuantifiCare 3D LifeViz® Mini imaging system by aligning the pre- and post-procedure images and measuring the change in position of numerous points on the face. The measurements were divided into categories of ≥0.5 mm, ≥1.0 mm, ≥1.5 mm, ≥2.0 mm, ≥2.5 mm. Results of measurements are presented in Table 3

Table 3 Percentage of subjects with Quantificare 3D lifting measurements

On both sides of the face, measurable improvement was demonstrated. All subjects experienced a lifting effect of ≥1.0 mm on both face sides and in the majority (>80%) lifting was ≥1.5 mm reflecting the general efficacy of threads. Overall, the size of the lifting effect was similar for both NAMICA threads and the third generation EVHA threads. However, after one month, 80% of the NAMICA-treated sides demonstrated a lifting of ≥2.0mm while it was only 52% for the sides treated with the third generation EVHA threads (Table 3).

Skin quality

Skin quality parameters, including wrinkles, evenness, and pores, were evaluated using the QuantifiCare 3D LifeViz® Mini system which provided objective measurements of skin texture, enabling a detailed analysis of treatment effectiveness over time. Separate assessments were conducted for wrinkles, skin evenness, and pores.

Face wrinkles

The QuantifiCare system applies specific algorithms to identify wrinkles on the skin’s surface and analyze wrinkle depth, length, and other parameters. Both thread types demonstrated statistically significant wrinkle reduction (Friedman’s test, p<0.001), with all patients (100%) showing improvement at 1 month and 3 months, and 96% of patients maintaining improvement at 6 months for both groups.

Both thread types demonstrated statistically significant wrinkle reduction (Friedman’s test, p<0.001), with all patients (100%) showing improvement.

The wrinkle scores at baseline and study timepoints are presented in Figure 1 While both treatments were effective, the effect of NAMICA technology was stronger than that of the third generation threads. By 1 month, the improvement in the skin quality on the NAMICAtreated face side was significantly higher than on the side treated with third generation threads (Wilcoxon test, p<0.01). This superiority was retained at 3 and 6 months, with NAMICA threads showing greater improvement compared to the EVHA third generation threads (Figures 1–2).

Skin evenness

The QuantifiCare 3D LifeViz® Mini system measures skin evenness by analyzing the uniformity of skin tone and texture across the facial surface. The evenness scores at baseline and study timepoints are presented in Figure 3 Both thread types significantly improved skin evenness over time (p<0.01, Friedman’s test). The improvement in evenness with the NAMICA technology threads was significantly greater than that of the EVHA threads (Wilcoxon test, p<0.01), which was retained for up to 6 months (Figures 3–4).

Figure 1 Wrinkles assessment with Quantificare 3D LifeViz® Mini system

Figure 2 Evaluation of wrinkles with QuantifiCare 3D LifeViz® Mini imaging system

Skin pores

The QuantifiCare 3D LifeViz® Mini system measures skin pore quality by analyzing pore size, density, and distribution on the skin’s surface using advanced 3D imaging and analysis tools. Improvement in skin pores was statistically significant for both NAMICA- and third generation EHVA-treated sides. The duration of changes was similar on the NAMICA- and EHVA-treated sides, however stronger improvement from baseline was noted on the NAMICA-treated sides 6 months after implantation (p<0.05, Figures 5-6).

Thus, this pilot study demonstrated a strong lifting effect and wrinkle improvement as well as high GAIS scores from the patient and doctor for both thread types. One month after implantation, the NAMICA threads attracted a greater proportion of the highest GAIS score assigned by the physician compared to the third generation EVHA threads. Using the Quantificare 3D LifeViz® Mini system the study demonstrated stronger improvement in skin quality (wrinkles, pores, evenness) in the sides of the face treated with the fourth generation of EVHA threads with NAMICA technology compared to the previous generation.

Adverse events

All adverse effects of thread implantation were evaluated for severity, frequency, and mean duration. Overall, adverse events were mild to moderate and resolved within a short time, and there were no severe events reported on either side.

All adverse effects observed in the study, were expected and typical for thread lifting. The most frequently occurring were swelling and edema. Mild swelling was observed both after NAMICA threads insertion (in 92% of patients) and after third generation EVHA treads (in 76%), as well as mild erythema (in 92% and 88% for NAMICA and third generation HA theads, respectively). Moderate swelling was more rare and occurred in 24% of subjects on the third generation HA-treated side and in 8% of NAMICA-treated sides, respectively. Other adverse events, such as pain, discomfort, bruising, and the feeling of warmth, were predominantly mild on both sides (Figure 7).

The duration of swelling was an average 8.4 days for the third generation EVHA threads and 6.6 days for the NAMICA threads. Pain lasted an average of 3 days for the third generation EVHA threads and 2.3 days for NAMICA threads. Discomfort persisted a little bit longer after the procedure with third generation EVHA threads (9 days) than in cases using the NAMICA threads (6.3 days) (Figure 8).

Thus, the safety profile of EVHA with NAMICA threads was close to the third generation EVHA threads with an overall trend toward shorter symptom duration.

Discussion

Thread lifting is an effective, minimally invasive procedure offering significant aesthetic improvements with reduced downtime compared to surgical options. This study evaluated the effectiveness and safety of the fourth generation of Aptos Visage Excellence P(LA/CL) threads enriched with hyaluronic acid by means of NAMICA technology. Each of the study subjects was implanted

Figure 3 Evenness assessment with Quantificare 3D LifeViz® Mini system

Figure 4 Evaluation of evenness with QuantifiCare 3D LifeViz® Mini imaging system

Data

A) Face side treated with NAMICA threads, before the procedure and after 6 months. B) Face side treated with third generation EVHA threads, before the procedure and after 6 months.

5 Pore assessment with Quantificare 3D LifeViz® Mini system

with NAMICA threads on one side of the face and with third generation EVHA threads on the other side. This split-face design, including side-by-side comparisons of the same patients and objective Quantificare 3D imaging assessments, allowed the authors to reduce potential bias. Assessments focused on the lifting effect, skin quality, and patient safety. Overall, the threads used in the study provided a strong lifting effect. The fourth generation NAMICA technology threads and the third generation EVHA threads were similarly highly effective in lifting, which was expected as the lifting procedure methodology, thread composition and physical properties of these thread types, aside from HA coating, were the same. At the same time, the study showed that fourth generation NAMICA technology threads outperformed third generation EVHA threads in all skin quality parameters, measured with the Quantificare 3D imaging system, including wrinkles, skin evenness and

pores. This is in line with the main feature of NAMICA technology involving gradual HA release and associated enhanced hydration, elasticity, and better skin texture. Finally, the beneficial effect of NAMICA threads was reflected in the greater percentage of study subjects receiving the highest GAIS score from the physician.

Our findings align with previous data comparing P(LA/ CL) threads to Visage Excellence Method P(LA/CL)+HA threads and add to evidence of high effectiveness of HAenriched P(LA/CL) threads15,20. The adverse effects observed in this study were expected, which means they have been reported previously, analyzed and considered typical for thread lifting procedure21. Mild swelling was the most common side effect in our cohort, there were no complications such as thread extrusion or dimpling. This highlights the safety and tolerability of NAMICA

References

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Figure 6 Evaluation of pores with QuantifiCare 3D LifeViz® Mini imaging system

A) Face side treated with NAMICA threads, before the procedure and after 6 months.

B) Face side treated with 3rd generation EVHA threads, before the procedure and after 6 months.

Figure

technology threads, attributable to their advanced design and gradual HA release, which minimizes inflammation and enhances recovery. Overall, the use of NAMICA technology would be beneficial for patients seeking skin quality improvement in addition to face lifting.

Conclusion

This study highlights the significant advantages of fourth generation EVHA threads with NAMICA technology over third generation EVHA threads in skin quality improvement along with a strong lifting effect. These findings suggest NAMICA threads may be a better option for thread lifting. NAMICA technology threads, with their combined mechanical lifting and biorevitalization effects through gradual HA release, provided superior lifting results, as confirmed by physician provided GAIS scores. Future research should explore larger cohorts and longer follow-ups to further establish its long-term benefits and mechanisms.

Declaration of interest Dr. George Sulamanidze has ownership interest in medical products and techniques of Aptos LLC. Dr. Igor Gulyaev is APTOS’ methods trainer.

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Figure 8 Duration of adverse effects (recovery symptoms)

Key points

NAMICA technology threads combine mechanical lifting with gradual HA release, enhancing skin quality, elasticity, and hydration alongside a strong lifting effect

Compared to thirdgeneration EVHA threads, NAMICA threads demonstrated significantly better results in reducing wrinkles, improving skin evenness, and minimizing pores, as shown through QuantifiCare 3D imaging.

NAMICA threads exhibited shorter durations of side effects like swelling and discomfort, highlighting their advanced design and superior safety profile.

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14. Goomer RS, Leslie K, Maris T, Amiel D. Native Hyaluronan Produces Less Hypersensitivity Than Cross-linked Hyaluronan. Clinical Orthopaedics and Related Research. 2005;&NA;(434):239-245. doi:https://doi.org/10.1097/01. blo.0000152443.04202.43

15. Kajaia A, Facial Rejuvenation with a New Generation of Combined Poly-L-Lactic Acid and Polycaprolactone Threads with HA. Prime Journal. 2024; January/February:18-22.

16. Lee D, Choi H, Yoo K, et al. Assessment of current practices and perceived effectiveness

The employment and ownership relationships have neither any interference with the activities and the results of this study nor the ability of the authors to process the reported material fairly, rationally and without any kind of bias.

Ethical Statement This research study was approved by the Ethics Committee of the Clinic of Plastic and Aesthetic Surgery and Cosmetology ‘Total Charm Vake’, Tbilisi, Georgia and Ethics Committee of the Clinic of Plastic and Aesthetic Surgery and Cosmetology ‘Total Charm Moscow’, Moscow, Russia, Written consent to reproduce their recognizable photographs, use anonymized clinical data for analysis and consent for publication was obtained from every study subject before initiation of any study procedure.

of injectable polynucleotide for enlarged facial pores among cosmetic physicians: A survey‐based evaluation. Skin Research and Technology. 2024;30(9). doi:https://doi. org/10.1111/srt.13738

17. Marefat A, Dadkhahfar S, Tahvildari A, Robati RM. The efficacy of polycaprolactone filler injection on enlarged facial pores. Dermatologic Therapy. 2022;35(8). doi:https://doi.org/10.1111/dth.15600

18. Shoshani D, Markovitz E, Monstrey SJ, Narins DJ. The Modified Fitzpatrick Wrinkle Scale: A Clinical Validated Measurement Tool for Nasolabial Wrinkle Severity Assessment. Dermatologic Surgery. 2008;34(s1):S85-S91. doi:https://doi. org/10.1111/j.1524-4725.2008.34248.x

19. Narins RS, Brandt F, Leyden J, Lorenc ZP, Rubin M, Smith S. A Randomized, Double-Blind, Multicenter Comparison of the

Efficacy and Tolerability of Restylane Versus Zyplast for the Correction of Nasolabial Folds. Dermatol Surg 2003; 29:588–95. org/10.1046/j.1524-4725.2003.29150.x.https://doi.

20. Jendrysik B, Kadjaia A, Sulamanidze G. Comparison of the Influence of New Generation Threads P(LA/ CL) HA And P(LA/ CL) on Convalescence and Clinical Effects in Patients Undergoing Minimally Invasive Anti-Aging Treatments. Clinical Dermatology Open Access Journal. 2020;5(1). doi.org/10.23880/cdoaj-16000204doi:https://

Niu Z, Zhang K, Yao W, et al. A Meta-Analysis and Systematic Review of the Incidences of Complications Following Facial Thread-Lifting. Aesthetic Plastic Surgery. 2021;45(5):2148-2158. org/10.1007/s00266-021-02256-wdoi:https://doi.

BIOSTIMULATORY INJECTIONS

RESTORING YOUTHFUL CONTOURS AFTER OZEMPIC AND BUCCAL FAT REMOVAL

With the rise of Ozempic-induced facial volume loss and buccal fat removal procedures, Summer Wong, Kawaiola Cael Aoki, Simona Bartos and Shino Bay Aguilera explore the rise of biostimulatory injections as a key solution for restoring youthful contours

SUMMER WONG, Doctor of Osteopathic Medicine (D.O.) Candidate, Fort Lauderdale, FL, USA;

KAWAIOLA CAEL AOKI, Doctor of Osteopathic Medicine (D.O.) Candidate, Fort Lauderdale, FL, USA; SIMONA BARTOS, DO, Imperial Dermatology, Hollywood, FL; SHINO BAY AGUILERA, MD, Shino Bay Cosmetic Dermatology and Laser Institute, Fort Lauderdale, FL, USA; email: shinobay@yahoo.com

KEYWORDS

Ozempic, Biostimulators, facial volume loss, fat loss

ABSTRACT

The escalating global challenge of metabolic syndrome has led to an increased interest in pharmacological interventions such as Ozempic (semaglutide) for glycemic management and weight loss. Although lifestyle interventions remain the first-line treatment for Type 2 Diabetes, sustainability is often difficult, leaving medications as a frequent alternative. Ozempic, approved by the Food and Drug Administration (FDA) for Type 2 Diabetes and cardiovascular disease risk reduction, continues growing in popularity for its off-label use in waeight loss, a trend prominently featured on social media and endorsed by online ‘influencers’. However, this widespread use has visible consequences, such as youthful volume loss, creating a prematurely aged appearance in a characteristic phenomenon

THE FIELD OF FACIAL AESTHETICS SHIFTS with changing norms and beauty standards. Currently, social media plays an outsized role in shaping the intersection of health and beauty trends and, therefore, on aesthetic disciplines and their practitioners. The widespread adoption of offlabel uses for medications like Ozempic for weight loss and the surging popularity of buccal fat removal procedures have created novel challenges in aesthetic dermatology. While inarguably effective in their intended purposes, these interventions have unintended consequences on facial aging, leading to phenomena often referred to as ‘Ozempic Face’ and concerns about midface distortion following buccal fat removal. The momentum of these trends on platforms such as TikTok and Instagram necessitates equally met solutions that effectively correct and compensate for facial volume loss and contouring. This review explores the anticipated shift towards biostimulatory injectables, including Radiesse (calcium hydroxylapatite), Sculptra (poly-L-lactic acid), and Renuva (allograft fat matrix) as a response to the changing norms in facial aesthetics. These injectables, known for stimulating a body’s innate collagen production and fat production

some now refer to as ‘Ozempic Face.’ In a global moment of parallelism, aesthetic trends such as buccal fat removal reshape facial contours but accelerate facial aging, a less discussed but increasingly evident concern. In response to these new challenges in aesthetic dermatology, we predict a trend towards biostimulatory injectables such as calcium hydroxyl apatite (CaHA), poly-L-lactic acid (PLLA), polycaprolactone (PCL), and off-the-shelf allograft adipose matrix. These injectables, known for stimulating collagen production and de novo fat production, providing longer-lasting results, will likely come to represent a cornerstone in aesthetics as practitioners and patients seek a way to restore natural facial contours and effectively address the accelerated aging associated with the widening footprint of weight loss and cosmetic trends.

providing durable results, are vital for restoring natural facial contours and addressing the accelerated aging associated with these trends. This shift will also highlight the need for further research into these treatments’ long-term efficacy, safety, and patient satisfaction in facial rejuvenation.

The triangle of youth

The youthful face is conventionally described as an inverted triangle shape, where the tip points downwards. It is customary to assess its symmetry and balance by dividing the face into horizontal thirds: the top third extends from the hairline to the glabella, the middle spans from the glabella to the subnasal region, and the bottom from the subnasal region to the mentum1. A youthful facial appearance is characterized by the harmonious interplay of superficial and deep fat, culminating in a well-rounded three-dimensional structure distinguished by graceful arcs and convexities2. Understanding the different adipose compartments is imperative for evaluating, appreciating, and treating facial aesthetics. Each region has specific characteristics, roles, and functions that are essential in maintaining

The widespread adoption of offlabel uses for medications like Ozempic for weight loss and the surging popularity of buccal fat removal procedures have created novel challenges in aesthetic dermatology.

balanced beauty in the face. These compartments include the nasolabial, medial cheek, orbital, and buccal fat1. The buccal fat compartment is essential in facial aesthetics, as excessive buccal extension can result in a rounded face, overly prominent cheeks, or the perception of a ‘baby face’3.

Facial fat alterations and aging

Facial fat alterations, both interventional and natural, play a significant role in visual aging, leading to changes in volume, atrophy, and migration of fat compartments. These changes result in a loss of contours and volume, leading to an upright triangle shape compared to a more youthful face1. The aging process manifests as a loss of soft tissue fullness in specific areas such as the periorbital, forehead, malar, temporal, mandibular, mental, glabellar, and perioral sites, coupled with the persistence or hypertrophy of fat in regions such as the submental, lateral nasolabial fold and labiomental crease, jowls, infraorbital fat pouches, and the malar fat pad.

Furthermore, the midface experiences age-related loss of subcutaneous fullness in the malar prominence, contributing to progressive buccal hollowing and a less healthy facial proportion2. While some individuals may experience loss of subcutaneous tissue in the eyelid, leading to a sunken appearance, the malar region can be affected by the loss of buccal fat volume, situated between the masseter muscle anteriorly and the buccinator muscle posteriorly. Atrophy of fat over the frontal process of the zygomatic bone and superior zygomatic arch particularly affects the upper region of the orbit and contributes to a sunken, aged appearance.

It is also important to understand the essential role that subcutaneous fat plays in maintaining the health and appearance of the skin. Subcutaneous fat is a protective cushion, absorbing mechanical impacts and minimizing external damage. It supports the skin’s natural barrier function by producing lipids necessary for maintaining the stratum corneum, the outermost layer of the skin. This layer shields against environmental stressors like pollutants, UV radiation, and pathogens, all contributing to premature aging. Beyond providing volume, subcutaneous fat is a structural cushion and a source of essential fatty acids, supporting skin cell regeneration and protecting against oxidative damage4. Additionally, subcutaneous fat contains adipose-derived stem cells (ASCs) that promote collagen production and skin repair, enhancing elasticity and slowing the aging process. These stem cells secrete growth factors that improve collagen and elastin production, supporting wound healing and overall skin quality. Therefore, the stem cells within the subcutaneous fat layer are particularly valuable for skin regeneration, making them a key focus in anti-aging and regenerative treatments in aesthetic medicine5

Patients experiencing significant weight loss often experience accelerated cervicofacial aging and can appear up to five years older than peers of a similar age without a history of extensive weight loss.

The age of Ozempic

Diabetes represents a significant and growing public health challenge worldwide. Current estimates indicate that approximately 415 million people globally are affected by this condition, with projections suggesting a rise to 642 million by 20406. Although lifestyle interventions such as diet and exercise are the historical mainstay of diabetes management and weight loss, sustainability proves difficult for many. Given these challenges, coupled with global trends toward quick fixes and instant gratification, injectable solutions have exploded in recent years. Ozempic, known generically as semaglutide, is a glucagon-like peptide-1 (GLP-1) receptor agonist. GLP-1 agonists effectively delay gastric emptying, suppress appetite, stimulate insulin release from pancreatic islets, and inhibit post-meal glucagon secretion. At its maximum dosage of 2 mg injected subcutaneously once weekly, Ozempic can lead to significant long-term weight loss and improved glycemic control7. The FDA approved Ozempic in 2017 for treating Type 2 Diabetes and reducing cardiovascular disease risk. Yet, its off-label use for weight loss is on the rise, especially in the last two years8

Ozempic has gained widespread popularity in the United States, highlighted in mainstream and social media for its dramatic weight loss effects9. Models and ‘influencers’ increasingly and loudly promote injectable weight loss medications on their TikTok and Instagram accounts. Weight Watchers, the top physician-recommended weight loss program, has also openly endorsed these medications and recently introduced a new GLP-1 program on their website to educate users and provide support10. Over the past five years, the relative search volume (RSV) for ‘Ozempic’ has increased exponentially, indicating a growing public interest in this class of medications9.

The ‘Ozempic Face’

Patients on Ozempic report an up to 20% loss in their total body mass10. However, excessive weight loss can lead to undesirable changes in facial structure, such as the depletion of lateral temporal and middle-fat pads and decreased skin laxity, resulting in an increased hollowedout appearance. Celebrity dermatologist Dr. Paul Jarrod Frank subsequently coined the term ‘Ozempic Face’ to describe this characteristic phenomenon8. Patients experiencing significant weight loss often experience accelerated cervicofacial aging and can appear up to five years older than peers of a similar age without a history of extensive weight loss11. This mimics the volume changes associated with natural aging, particularly the thinning of subcutaneous tissue in critical facial regions. Moreover, the rapid loss of fatty acids and essential nutrients may compromise the skin barrier, affecting

texture and leading to a deflated and dull appearance. Therefore, patients experiencing more skin laxity tend to experience more pronounced wrinkles. Across all age groups, patients frequently and inappropriately escalate their Ozempic dosage to the maximum, resulting in a significantly reduced appetite. Such aggressive weight loss, especially when combined with a protein-deficient diet, can exacerbate facial ageing by creating muscle wasting in the face and fat loss12. These effects are particularly pronounced in older adults, whose skin naturally contains less collagen and elastin8. The loss of facial fat in critical areas like the temples, cheeks, tear troughs, and jawline due to Ozempic-induced rapid weight loss can significantly impact facial structure.

Weight loss in adipose tissue is not site-specific; it can occur in problematic areas such as the thighs or abdomen as readily as in the youthful, healthy adipose tissue of the cervicofacial regions. Current clinical trials fail to report changes in facial structure as a potential adverse effect of this medication. As a result, cosmetic dermatologists are increasingly tasked with addressing rapid, sometimes progressive, facial volume loss caused by Ozempic and similar drugs8.

Buccal fat removal

On the surgical end of interventions, buccal fat removal is a trend gaining significant traction in aesthetic circles and is vocally touted by influencers on social media. The buccal fat pad is a biconvex, encapsulated structure situated in the buccal space, bordered medially by the buccinator muscle, anterolaterally by the deep cervical fascia and facial expression muscles, and posteriorly by the parotid gland. It consists of three lobes: anterior, intermediate, and posterior. The posterior lobe features four extensions, including the buccal, pterygopalatine, pterygoid, and temporal processes. For midfacial contouring, only the body and buccal extension of the BFP are typically removed, which together represent 55% to 70% of the BFP’s total volume.

Individuals who have undergone buccal fat removal have taken to social media platforms, sharing personal accounts and online reviews, to seek treatment for the hollowed and gaunt-like appearance that resulted from their procedure.

lower thirds of the face, and enhancing features like the zygomatic bone and jawline. Injuries to the facial nerve branches, which can cause symptoms like ptosis, facial numbness, tingling, and even a metallic taste in the mouth, are rare but well-known and reported complications. Despite the initial positive effects on facial aesthetics and low postoperative complication rates, the lack of long-term data should warrant caution in using buccal fat pad resection for mid-face enhancement until more research becomes available14

Buccal fat removal midface distortion

Buccal fat removal also seems to inadvertently replicate volume changes observed during aging, which is a less frequently discussed but important long-term consequence15. Buccal fat pad growth increases between the ages of 10 and 20 (4000 to ) and then decreases over the next 30 years (declining to 7000 mm3); surgical excision of this fat pad will likely result in hanging jowls, midface distortion, and altered facial proportions over time; thereby echoing the age-related loss of subcutaneous fullness and progressive buccal hollowing in natural aging16. Individuals who have undergone buccal fat removal have taken to social media platforms, sharing personal accounts and online reviews, to seek treatment for the hollowed and gaunt-like appearance that resulted from their procedure. There is a gap in the literature regarding the long-term sequelae of buccal fat removal in facial aging, which needs to be addressed15

According to the Aesthetic Plastic Surgery National Databank, buccal fat removal procedures saw a 68% increase from 2020 to 2021 and a further 7% increase between 2022 to 202313. Celebrities such as Chrissy Teigen, Bella Hadid, and Zoe Kravitz have reportedly undergone this procedure. Excision of the buccal fat pad is known for creating a more aesthetically pleasing mid-face, slimming the middle and

Biostimulatory injectables

The recent surge in weight loss injectables and buccal fat removal has presented a unique novel set of obstacles for cosmetic dermatologists. While effective for weight loss and facial contouring, respectively, these methods often lead to accelerated cervicofacial aging in the long run.

The fat adipose matrix can imitate autologous fat with collagen, and clinicians are embracing it as a like-for-like approach. Such treatments not only restore natural facial contours but also improve skin texture, address facial lipoatrophy and wrinkles, and aid in balancing facial proportions.

Biostimulatory injectables, including calcium hydroxylapatite (CaHA), poly-L-lactic acid (PLLA), and allograft fat matrix, may offer a personalized approach for the affected population. When injected, these biodegradable, volumizing injectables induce a foreign body inflammatory response, which promotes collagen synthesis by fibroblasts in the extracellular matrix. This process stimulates the body’s natural collagen and elastin production, leading to outcomes that may last for up to two years. In a similar vein, the fat adipose matrix can imitate autologous fat with collagen, and clinicians are embracing it as a like-for-like approach. Such treatments not only restore natural facial contours but also improve skin texture, address facial lipoatrophy and wrinkles, and aid in balancing facial proportions17

Hyaluronic acid fillers may be used to address volume loss, though they offer only a temporary and potentially expensive solution. In comparison, biostimulatory injectables provide a more cost-effective and long-lasting approach, yielding sustained results through continuous collagen stimulation. While pursuing both weight management and cosmetic enhancement, a trend toward using biostimulatory injectables should be anticipated and encouraged as a promising solution for preserving or even restoring youthful facial contours.

The rapidly evolving trends in cosmetic dermatology pose significant challenges for practitioners, highlighting the need for ongoing research and innovation. These

References

1. Coimbra DDA, Uribe NC, Oliveira B. Facial squaring in the aging process. Surg cosmet Dermatol. 2014;6:65-71.

2. Coleman SR, Grover R. The anatomy of the aging face: volume loss and changes in 3-dimensional topography. Aesthetic surgery journal. 2006;26(1_ Supplement):S4-S9.

3. Moura L-B, Spin J-R, Spin-Neto R, Pereira-Filho V-A. Buccal fat pad removal to improve facial aesthetics: an established technique? Medicina oral, patologia oral y cirugia bucal. 2018;23(4):e478.

4. Wollina U, Wetzker R, Abdel-Naser MB, Kruglikov IL. Role of adipose tissue in facial aging. Clin Interv Aging. 2017;12:2069-2076. doi:10.2147/CIA.S151599

5. Ritter A, Friemel A, Roth S, et al. Subcutaneous and Visceral Adipose-Derived Mesenchymal Stem Cells: Commonality and Diversity. Cells. Oct 21 2019;8(10) doi:10.3390/cells8101288

6. Al-Lawati JA. Diabetes Mellitus: A Local and Global Public Health Emergency! Oman Med J. May 2017;32(3):177-179. doi:10.5001/omj.2017.34

7. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in

Key points

The popularity of weight loss medications like Ozempic and procedures like buccal fat removal is reshaping cosmetic dermatology, presenting challenges such as accelerated facial aging and altered facial structures.

Treatments such as Radiesse, Sculptra, and Renuva are gaining prominence for their ability to restore facial volume, stimulate collagen production, and address the effects of volume loss caused by these trends

Ongoing advancements in cosmetic treatments are essential to meet the dynamic demands of modern aesthetic standards while ensuring safety, efficacy, and patient satisfaction

dynamic demands of the contemporary medical landscape require practitioners striving for optimal outcomes to stay updated on the latest advancements and techniques to provide optimal patient care.

Conclusion

The rising use of weight loss medications like Ozempic and aesthetic procedures such as buccal fat removal has significantly impacted the field of cosmetics. While these interventions offer benefits in weight management and facial contouring, they also present hurdles, particularly in accelerating facial aging and altering facial structures. Biostimulatory injectables provide a key solution for the immediate concerns of facial volume loss and offer a longerterm strategy to preserve youthful facial contours. This predictable trend will highlight the importance of ongoing research and development in cosmetic dermatology, ensuring that treatments keep pace with evolving aesthetic trends and the needs of diverse patient populations.

Declaration of interest The authors of this manuscript have no conflicts of interest to disclose.

Acknowledgements The authors would like to thank Chris Kowalczyk for his contribution to the manuscript.

Adults with Overweight or Obesity. N Engl J Med. Mar 18 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183

8. Humphrey CD, Lawrence AC. Implications of Ozempic and Other Semaglutide Medications for Facial Plastic Surgeons. Facial Plast Surg. Dec 2023;39(6):719-721. doi:10.1055/a-2148-6321

9. Han SH, Safeek R, Ockerman K, et al. Public Interest in the Off-Label Use of Glucagon-like Peptide 1 Agonists (Ozempic) for Cosmetic Weight Loss: A Google Trends Analysis. Aesthet Surg J. Dec 14 2023;44(1):60-67. doi:10.1093/asj/sjad211

10. Jewell ML. Commentary on: Aesthetic Surgery Journal Articles on Injectable Weight Loss Medications and Their Role in Plastic Surgery. Aesthet Surg J. Dec 14 2023;44(1):80-83. doi:10.1093/asj/sjad263

11. Couto RA, Waltzman JT, Tadisina KK, et al. Objective Assessment of Facial Rejuvenation After Massive Weight Loss. Aesthetic Plast Surg. Dec 2015;39(6):847-55. doi:10.1007/s00266-015-0540-6

12. Suran M. As Ozempic’s Popularity Soars, Here’s What to Know About Semaglutide and Weight Loss. JAMA. May 16 2023;329(19):1627-1629. doi:10.1001/ jama.2023.2438

13. The American Society of Plastic Surgeons (ASPS). ASPS 2023 Procedural Statistics Release. 2024.

14. Traboulsi-Garet B, Camps-Font O, Traboulsi-Garet M, Gay-Escoda C. Buccal fat pad excision for cheek refinement: A systematic review. Med Oral Patol Oral Cir Bucal. Jul 1 2021;26(4):e474-e481. doi:10.4317/medoral.24335

15. Benjamin M, Reish RG. Buccal Fat Pad Excision: Proceed with Caution. Plast Reconstr Surg Glob Open. Oct 2018;6(10):e1970. doi:10.1097/ GOX.0000000000001970

16. Rohrich RJ, Stuzin JM, Savetsky IL, Avashia YJ, Agrawal NA, Prada M. The Role of the Buccal Fat Pad in Facial Aesthetic Surgery. Plast Reconstr Surg. Aug 1 2021;148(2):334-338. doi:10.1097/PRS.0000000000008230

17. Haddad S, Galadari H, Patil A, Goldust M, Al Salam S, Guida S. Evaluation of the biostimulatory effects and the level of neocollagenesis of dermal fillers: a review. Int J Dermatol. Oct 2022;61(10):1284-1288. doi:10.1111/ijd.16229

RECOMBINANT ENZYMES A NEW PATHWAY INTO FACIAL RESHAPING AND SKIN REJUVENATION

Jan Balczun, MD, and Nuria Ramirez, MD, highlight the synergistic power of recombinant enzymes in facial reshaping and skin rejuvenation, offering safe, effective, and substrate-specific solutions

email: info@balczun.de

KEYWORDS

Facial aesthetics, injectables, non-surgical facial rejuvenation, enzymes

ABSTRACT

Advances in biotechnology have revolutionized aesthetic medicine, introducing recombinant enzymes as safe and effective tools for facial reshaping and skin rejuvenation. These enzymes, including collagenase, lipase, and lyase, act synergistically to address various tissue concerns

OVER THE PAST FEW DECADES, AN ever-growing number of technological advancements have provided us with a broader range of methods to treat our patients, ensuring optimal results and high patient satisfaction.

One notable advancement over the past 30 years is the research and subsequent development of proteins. These proteins, specifically enzymes, have become valuable tools in a variety of industries, and their medical applications are the focal point of this article1.

Facial reshaping and skin rejuvenation are primary concerns within the field of facial aesthetics. These issues stem from numerous underlying causes, such as changes in all layers of facial tissues, including bone resorption, subcutaneous fat pad repositioning due to ligament laxity and hypertrophy, and skin atrophy and sagging2

The lower third of the face is often targeted for facial reshaping. However, it presents a significant challenge due to the complexity of addressing multiple structures when establishing a treatment plan. The use of recombinant enzymes in this context has proven to be a safe and effective treatment option.

For starters, what is a recombinant enzyme?

In vivo enzymatic production is a complex mechanism closely entwined with gene expression, the process in which the information encoded in the DNA polymer is translated. The resulting proteins are tightly regulated through various mechanisms to meet specific needs3

such as fat deposits, collagen degradation, and extracellular matrix remodeling. Their substrate-specific action ensures minimal side effects and high patient satisfaction. This review highlights the mechanisms, applications, and benefits of enzymatic treatments, underscoring their transformative potential in modern aesthetic practice.

The increasing demand for enzyme availability across different industries for larger quantities, faster production, and lower costs has led to the creation of in vitro systems, or so-called heterologous expression, where these proteins can be created on demand: recombinant technology

To achieve a specific, safe, and effective enzyme, the most popular host known so far is gram-negative However, other types of surrogates are also used depending on the field of application. The popularity of E. coli in the genetic engineering field is mainly due to its well-known characterization, complete genome sequence knowledge, and understanding of its biological and metabolic pathways, making it a widely recognized workhorse for genetic manipulation5

Mahmoud (2007) best describes the process of recombination in his article6: ‘To produce a protein heterologously in a living host, the target DNA-coding sequence must be known, and a suitable transformation and selection strategy must exist. Cloning the coding DNA into a suitable vehicle is a prerequisite for introducing it into the selected host. This vehicle is usually called a vector. This vector is typically an independently replicating DNA or at least a DNA segment that can integrate into the expression host genome.’

Enzymes in aesthetics

For as many enzymes that have been developed within the medical field, our focus in this article is the introduction of those entering the field of aesthetics, specifically collagenase G/H PB 220, lyase PB72K,

JAN BALCZUN, MD, Facial Plastic Surgeon , Bochum, Germany; NURIA RAMIREZ, MD, Aesthetic Medicine, Madrid, Spain

reducing the molecular weight of these fragments8

Another significant enzyme is recombinant lipase, a protein that belongs to the triacylglycerol acylhydrolases. Its mechanism of action is to catalyze the hydrolysis of triacylglycerols to glycerol and free fatty acids on its ester bonds in the adipose tissue. E. coli is the most widely used host for the heterologous expression of this particular enzyme9

Lipase’s significant safety and strong differentiating element set it apart from other lipolytics, as it keeps the cell membranes intact and healthy, only affecting the fat droplet within. It is also important to note that recombinant lipase is not hormone-dependent.

This results in minimal side-effects, reduced clinical complications, and the achievement of good results in a short period of time.

Finally, recombinant lyases are enzymes that catalyze the breaking of a chemical bond between two parts of a molecule by pathways other than hydrolysis and oxidation, often forming a double bond or adding a new ring to the targeted structure10

Their mechanism of action involves directly acting on

demand for enzyme availability across different industries for larger quantities, faster production, and lower costs has led to the creation of in vitro systems, or so-called heterologous expression, where these proteins can be created on demand: recombinant technology.

Their breakdown results in two main situations: liquefaction of the matrix, allowing other substances to travel more efficiently in a more physiological environment, and the release of growth factors, cytokines, and chemokines, which act as key modulators for tissue remodeling and development, restoring signaling pathways and cell-to-cell interactions11

A synergistic machinery

As described previously, recombinant enzymes have very specific functions based on their substrates. However, their true value within the medical and aesthetic fields lies in the combination of all three enzymes.

The integration of different metabolic pathways provides a synergistic approach to treatment. To expand, collagen degradation through recombinant collagenase is instrumental in breaking down non-functional collagen, which leads to the stimulation of fibroblast proliferation, chemotaxis, and angiogenesis. These processes directly impact skin rejuvenation and tightening, enhancing the skin’s overall appearance and texture.

When aiming for fat tissue lysis, recombinant lipase

targets the adipocyte without causing any harm to the cell membrane. This safety feature minimizes side-effects, making it an ideal option for fat reduction treatments. Lipase catalyzes the hydrolysis of triacylglycerols to glycerol and free fatty acids, effectively reducing localized adipose tissue.

Glycosaminoglycan fragmentation, related to recombinant lyase acting on the proteoglycan family, stimulates the repair and remodelling of the extracellular matrix, creating a more physiological intercellular space. This enhanced environment allows other enzymes to perform more effectively at their target sites and strengthens the structural scaffold of the tissue.

The combination of these enzymes forms a synergistic mechanism that addresses some of the main issues in the aesthetic field, such as localized adipose tissue, skin laxity, fibrosis, and scarring. When used together, these enzymes act at different tissue levels, resulting in more harmonious and effective solutions for both patients and doctors12

The synergistic effect of combining the three enzymes leads to improved outcomes in aesthetic treatments. For example, the degradation of proteoglycans by lyase within the extracellular matrix not only tightens the skin but also creates an optimal environment for lipase to reduce fat deposits without damaging cell membranes. Meanwhile, collagenase’s action ensures that the skin remains healthy and well-structured, promoting overall tissue repair and regeneration.

In summary, the integration of recombinant collagenase, lipase, and lyase in aesthetic treatments offers a comprehensive and effective approach. By targeting different aspects of tissue health and regeneration, this combination provides enhanced results, ensuring higher patient satisfaction and better clinical outcomes. This multifaceted approach represents a significant advancement in the field of aesthetic

Facial reshaping is a highly demanded yet complex procedure as it involves many structures, from bone resorption and ligament laxity to the descent of facial fat pads and skin sagging. This is where enzymatic usage plays a key role in restoring facial harmony.

medicine, showcasing the potential of recombinant enzymes to revolutionize treatment protocols14

Facial reshaping

As a result of the rising demand, the biotech field has developed many practical devices, mostly safe but sometimes carrying side-effects or leaving unwanted aesthetic marks. Recombinant enzymes, with their extensive background and research investment, are fundamental tools in the medical office when devising a treatment plan and making decisions regarding the physician’s treatment pathway. These enzymes can be used solo or in combination with other biocompatible agents.

Skin sagging can be targeted using a combination of all three enzymes with a higher concentration of collagenase. When applied at a dermal level, lyases will restructure and restore the extracellular matrix, lipase will target any surrounding fat deposits, and collagenase will play a key role by breaking down non-functional collagen and activating the signaling pathway in which fibroblasts undergo replication, consequently starting the neocollagenesis process.

Jowls and double chin can be addressed with a similar enzymatic cocktail but with a higher lipase concentration, targeting the fat tissue by degrading the triglyceride content and thus reducing its volume and weight, resulting in a

Keratinase

more contoured mandibular and/or neckline. Additionally, since collagenase is included in the cocktail, skin laxity due to fat loss will not be evident due to the previously explained process.

This enzymatic combination can be applied to any area of the face, neck, and body where reshaping and skin rejuvenation are desirable.

Regarding safety, enzymatic treatments have proven to be safe, with very few or no side effects, and are easy to use in practice. Their safety is attributed to the fact that enzymes are substratedependent.

In the field of aesthetics, there are a variety of feared adverse effects associated with the injector, technique, and product properties. However, if the enzymatic product migrates or is misplaced in a different layer than intended, no action will occur because there is no substrate for the enzyme to work on.

Additionally, the recombinant origin of these enzymes, which produces smaller molecules with fewer glycosylations, significantly reduces the risk of an allergic reaction, making it almost negligible.

In practice

In a clinical, open-label study, 18 patients were treated with a cocktail of recombinant enzymes (collagenase, lipase, and lyase), together with high molecular weight hyaluronic acid (HA), results showed significant improvement after 36 days of treatment, effective against skin flaccidity in 92%, improved firmness in 92% and reduced fat in 84%. Patient satisfaction was 93% and the procedure well tolerated15.

In another 2024 study, 9 out of 10 patients showed a considerable reduction of 22.8% in the patient-reported

References

1. Gomes C, Silva AC, Marques AC, Sousa Lobo J, Amaral MH. Biotechnology Applied to Cosmetics and Aesthetic Medicines. Cosmetics. 2020; 7(2):33. https://doi.org/10.3390/ cosmetics7020033

2. Braz A, Eduardo CCP. Reshaping the Lower Face Using Injectable Fillers. Indian J Plast Surg. 2020 Aug;53(2):207218. doi: 10.1055/s-0040-1716185. Epub 2020 Aug 29. PMID: 32884187; PMCID: PMC7458843.

3. Tripathi NK, Shrivastava A. Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development. Front Bioeng Biotechnol. 2019 Dec 20;7:420. doi: 10.3389/fbioe.2019.00420. PMID: 31921823; PMCID: PMC6932962.

4. Shashi Kant Bhatia, Narisetty Vivek, Vinod Kumar, Neha Chandel, Meenu Thakur, Dinesh Kumar, Yung-Hun Yang, Arivalagan Pugazendhi, Gopalakrishnan Kumar, Molecular biology interventions for activity improvement and

Key points

Recombinant enzymes, including collagenase, lipase, and lyase, target specific substrates, ensuring minimal side effects and improved clinical outcomes

The combination of enzymes enhances fat reduction, collagen remodeling, and extracellular matrix restoration for comprehensive facial reshaping and skin rejuvenation

Enzymatic treatments effectively address jowls, double chin, skin laxity, and other facial or body concerns, providing safe and harmonious results

sub-mental fat impact scale, while 9 of 10 expressed overall satisfaction with the treatment. Submental fat reduction of more than 10% was observed in 9 out of 10 patients and as the study concluded the enzymatic mixture of lipase, collagenase and hyaluronidase is an effective and safe minimally-invasive method for the reduction of submental fat16.

Conclusion

With many years of research investment in the field of biotechnology, specifically in recombinant enzymes and enzymatic systems, recombinant enzymes have proven fundamental in clinical practice. They demonstrate excellent results in both facial reshaping—targeting jowls, double chin and skin sagging—and overall skin rejuvenation.

This success is attributed to the synergistic effect of combining collagenase, lipase, and lyase, which act on different tissue structures to produce harmonious results without leaving aesthetic marks.

Moreover, this approach allows practitioners to use these enzymes in combination with other devices, ensuring high safety and proven efficacy.

In conclusion, the use of enzymatic treatments has demonstrated both efficacy and safety in skin rejuvenation and facial reshaping, making it a reliable and valuable option for practitioners.

Declaration of interest The author of this manuscript has no conflicts of interest to disclose.

production of industrial enzymes,

5. Mital, S., Christie, G. & Dikicioglu, D. Recombinant expression of insoluble enzymes in Escherichia coli: a systematic review of experimental design and its manufacturing implications. Microb Cell Fact 20, 208 (2021). https://doi.org/10.1186/s12934-021-01698-w

6. Mahmoud, K. (2007). Recombinant protein production: strategic technology and a vital research tool. Research Journal of Cell and Molecular Biology, 1(1), 9-22.

7. Starkweather, K. D., Lattuga, S., Hurst, L. C., Badalamente, M. A., Guilak, F., Sampson, S. P., ... & Wisch, D. (1996). Collagenase in the treatment of Dupuytren’s disease: an in vitro study. The Journal of hand surgery, 21(3), 490-495.

8. Cerveró, R. S., Herrero, D. G., & Hueso, F. J. C. (2016). Mechanism of action of collagenase clostridium histolyticum for clinical application. European journal of clinical

pharmacy: atención farmacéutica, 18(4), 263-272.

9. Contesini, F. J., Davanço, M. G., Borin, G. P., Vanegas, K. G., Cirino, J. P. G., Melo, R. R. D., ... & Carvalho, P. D. O. (2020). Advances in recombinant lipases: Production, engineering, immobilization and application in the pharmaceutical industry. Catalysts, 10(9), 1032.

10. Stern, R., & Jedrzejas, M. J. (2006). Hyaluronidases: their genomics, structures, and mechanisms of action. Chemical reviews, 106(3), 818-839.

11. Silva, J. C., Carvalho, M. S., Han, X., Xia, K., Mikael, P. E., Cabral, J. M., ... & Linhardt, R. J. (2019). Compositional and structural analysis of glycosaminoglycans in cell-derived extracellular matrices. Glycoconjugate journal, 36, 141-154.

12. Fierro-Arias, L., Campos-Cornejo, N. G., Contreras-Ruiz, J., Espinosa-Maceda, S., López-Gehrke, I., Márquez-Cárdenas, R., ... & Rodríguez-Alcocer, A. N. (2017). Productos enzimáticos (hialuronidasa, colagenasa y lipasa) y su uso en

Dermatología. Dermatología Revista Mexicana, 61(3).

13. López Gehrke I, Soto Montenegro AE, Santaella E, Prada Castellanos Y, López Berroa J. Degree of Satisfaction of Patients Treated Cosmetically with Recombinant Enzymes; Clinical Experience. Lat Am J Clin Sci Med Technol. 2024 Mar; 6: 47 - 55.

14. Berroa JL. Hyaluronic Acid and Recombinant Enzymes Pbserum Low for the Treatment of Sagging Body Skin. LJMHR [Internet]. 2024 Jul. 8 [cited 2025 Jan. 6];24(6):1-11.

15. Jabbour R, Farah F, Mallat F, Saad E, Semaan K, Haber R, Helou J. Efficacy and safety of the enzymatic mixtureLipase, collagenase and hyaluronidase - In the treatment of moderate to severe submental fat: A prospective cohort study. Heliyon. 2024 Feb 10;10(4):e25759. doi: 10.1016/j. heliyon.2024.e25759. PMID: 38375282; PMCID: PMC10875420.

MARCELO GERMANI DDS, M.SC, PH.D, Department of periodontology and implantology, University of Guarulhos, São Paulo, Brazil; VICTOR ROGERIO DDS, M.SC, Let’s HOF Academy, São Paulo, Brazil; GABRIELA GIRO

DDS, M.SC, PH.D , Department of periodontology and implantology, University of Guarulhos, São Paulo, Brazil; VICTOR R. M. MUNOZLORA DDS, PH.D, Department of periodontology and implantology, University of Guarulhos, and Let’s HOF Academy, São Paulo, Brazil

email: margermani@hotmail.com

INJECTING NEUROMODULATORS INTO THE UPPER DEPRESSOR MUSCLES TO TREAT FOREHEAD LINES

Marcelo Germani, Victor Rogerio, Gabriela Giro, and Victor

R.M. Munoz-Lora present a case study exploring a novel botulinum toxin approach targeting glabellar muscles for smoother foreheads and preserved eyebrow symmetry

ABSTRACT

The use of neuromodulators is currently the leading minimally invasive aesthetic treatment worldwide. Typically, these are applied across all facial muscles, with the main goal being to enhance the appearance by reducing muscle contraction at the specific injection site. The frontal region can benefit greatly from the temporary cessation of the frontal muscle’s contraction, which reduces wrinkles. However, as part of the muscle acts as a lifter and is responsible for eyebrow positioning, excessive doses in the area can lead to unsatisfactory effects, especially concerning the upper periorbital region and eyebrow placement. The objective of this case series was to isolate applications to only the antagonistic muscles to the frontal muscles, specifically the corrugator and procerus muscles, which are depressors. This approach demonstrates that by reducing the contraction ability of the region, its antagonist also benefits, thus decreasing muscle contraction and consequently improving the appearance of the region with a lower dose.

BOTULINUM TOXIN TYPE-A (BONT-A) APPLICATIONS FOR FACIAL aesthetics are one the top five non-surgical procedures according to the 2023 international survey on aesthetic/cosmetic procedures (ISAPS), accounting for 8,877,991 treatments performed in 2023 1 .

Aesthetic BoNT-A treatments are traditionally aimed at improving facial wrinkles. However, new concepts of facial biomechanics have also demonstrated tissue repositioning as an important outcome for facial rejuvenation following BoNT-A treatments2,3 . It was previously demonstrated that BoNT-A applications into lower depressors muscles (i.e. platysma and depressor anguli oris) resulted in lower and medial tissue repositioning2, as well as improvement of infraorbital hollows3. Additionally, short4 and long-term cumulative effects5 of BoNT-A application into the upper depressor muscles (i.e. procerus, corrugators, and orbicularis oculi) can lead to an improvement in the eyebrow height due to a muscle rebalancing in this area.

KEYWORDS

Forehead, neuromodulators, glabellar

Along with these facial lifting results, upper-third treatments with BoNT-A solely into the depressor muscles may improve forehead lines even without targeting this elevator muscle. Frequently, the frontalis muscle is targeted with high doses of BoNT-A for forehead line improvement6; however, this may not be convenient for long-term results of soft tissue cranial repositioning and eyebrow height since the frontalis is the only elevator of the upper third and the eyebrows. With this, we present five cases of improvement of forehead lines after solely treating the glabellar muscles, using a refined 3-point injection technique.

Improving forehead lines targeting solely glabellar muscles

Five patients attended the clinic looking for glabellar and forehead line improvement. After a detailed clinical evaluation, all patients were indicated for BoNT-A treatment on the upper third. A signed informed consent and authorization for photo use were obtained. The five participants were 39, 27, 35, 43, and 42 years old, respectively, and had not received neuromodulators for over 6 months prior to the present treatment.

BoNT-A was injected into the patients’ procerus and corrugator muscles and always administered by the same

Short and long-term cumulative effects5 of BoNT-A application into the upper depressor muscles (i.e. procerus, corrugators, and orbicularis oculi) can lead to an improvement in the eyebrow height due to muscle rebalancing in this area.

clinician. For this, abobotulinumtoxinA (Dysport, Galderma, Uppsala, Sweden) was prepared on the same day of treatment using 2 ml of sterile saline solution for each 500 sU of the toxin. Asepsis of the treated region was performed using 2% chlorhexidine, and topical anesthesia was applied

to the determined injection points. Injections were performed using a 31 G, 6 mm syringe (Becton Dickinson, Franklin Lakes, NJ, US). A refined 3-point injection technique7 was used to treat the procerus and corrugator muscles (Figure 1). For the corrugators, a single injection point was used at the medial and inferior margin of the upper orbit, with a 45-degree insertion angle of the needle in the direction of the midline and in contact with the bone. For the procerus, a deep injection point located between the medial canthal ligaments and in contact with the nasal bone was used. All injection points were caudally located to the eyebrow line, and 12.5 sU was used at each point.

Figure 1

The three-point injection technique to inject the procerus and corrugator muscles

Two dimensional and 3D photographs (Quantificare) were taken before and 30 days after BoNT-A injections. 3D photos were assessed using stereophotogrammetry software (DermaPix, Quantificare) for semi-quantitative analysis of tissue displacement in the frontal region. The results obtained are illustrated in Figures 2–4. The software was adjusted to display red arrows indicating a displacement of 5 mm or more with the participant in maximum contraction of the frontal region.

Fourteen days after treatment, the photographs of all five participants highlighted a significant improvement in the forehead lines. Additionally, 30 days after treatment, a noticeable reduction of red arrows pointing to a cranial direction was found (Figure 5). It is worth noting that there

was no caudal displacement of the eyebrow at rest in the post-treatment period, and the eyelid opening remained unchanged, as demonstrated in Figure 6. However, upon contraction of the frontal muscle, an unaltered displacement of the eyebrow is observed, indicating that the frontal muscle maintains its activity, as illustrated in Figure 7.

Discussion

The aesthetic application of BONT-A is a successful, wellestablished, minimally invasive procedure for treating facial wrinkles. However, new anatomical concepts, primarily related to facial biomechanics, must be considered when planning the areas of application if a lifting effect needs to be obtained8

Further emphasizing the concept of balance and movement among facial muscles, Germani and colleagues in 20232 demonstrated, through a clinical study, volumetric improvement and tissue displacement towards the upper third of the periorbital region in 35 patients. These individuals underwent BONT-A application along the jawline. In addition to quantitative analysis, positive qualitative evaluations regarding the treatment were also observed and reported by the participants themselves in the study.

Fourteen days after treatment, the photographs of all five participants highlighted a significant improvement in the forehead lines.

On the other hand, Ramos and colleagues, in a retrospective analysis, emphasize that whenever a muscle in a specific region is weakened, the balance of forces shifts, and the resulting vector is pulled more strongly in the opposite direction. According to the authors, when a muscle is paralyzed, other muscles may be activated with greater force, altering the direction of vectors and thus favoring the formation of wrinkles. However, what both the current literature and our series of cases demonstrate is quite the opposite9

Following the same concept, Solish and colleagues emphasize the importance of avoiding the application of BONT-A in the frontal muscle during the treatment of glabellar lines due to the adverse effects it can have on the position and symmetry of the eyebrows. When the lower part of the frontal muscle is exposed to BONT-A, it can disrupt the balance of forces between the elevators and depressors of the eyebrows, resulting in undesirable aesthetic outcomes such as excessive elevation of the lateral eyebrow compared to the medial, or drooping eyebrows, giving a tired or sad appearance10.

The reduction of wrinkles in the frontal region, observed after the application of botulinum toxin in the muscles of the glabellar complex (corrugators and procerus), can be attributed to the mechanism known as reciprocal inhibition11. This phenomenon occurs when botulinum

Figure 2 (A) Before and (B) after treatment

Figure 3 (A) Before and (B) after treatment

Figure 4 (A) Before and (B) after treatment

toxin reaches the muscles and prevents muscle contraction, resulting in the loss of muscle tone. Consequently, the affected muscle relaxes and elongates.

This increases the amplitude of movement in the target muscle of the botulinum toxin. On the other hand, the fibers of the antagonist muscle become shorter, increasing its tonus but diminishing its amplitude of movement12. This explains, for example, why the patient’s eyes appear to open further after injecting the toxin in the glabella and not injecting the frontalis muscle. The glabella muscles elongate, and the frontalis shorten. Furthermore, when the patient raises their eyebrows, the frontalis muscle works with less effort; this happens because the procerus and corrugators are partially paralyzed and offer less resistance than before. So, the frontalis muscle raises the eyebrows, using less effort and, consequentially, fewer wrinkles. The balance between elevator and depressor has changed and the frontalis muscle is now the predominant muscle working in the reciprocal inhibition mechanism11. This knowledge may also be applied to the whole face, as was seen in the lifting effect provoked by the botulinum toxin injected into the platysma muscle by Rogerio et al. 20223 That happened because the platysma is the major depressor of the face, and its blockage by the botulinum toxin changed the predominance in the reciprocal inhibition mechanism to the elevators of the medium and upper third of the face.

Conclusion

This series of clinical cases explored the application of BONT-A specifically in the depressor muscles of the face, such as the corrugator and procerus muscles, while avoiding the frontalis muscles. Preliminary results indicate a significant reduction in tissue displacement in the frontal region and aesthetic improvement in the area, with a noticeable decrease in muscle contraction. This approach not only smoothens dynamic wrinkles but also preserves eyebrow symmetry and aesthetics without any undesirable side effects.

Declaration of interest None

References

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2. Germani M, Almeida CCMS, Munoz-Lora VRM, Rogério V, Moelhoff N, Freytag DL, Green JB, Alfertshofer M, Davidovic K, Cotofana S. How to improve infraorbital hollows with neuromodulators-A clinical prospective interventional study about the application of facial biomechanics. J Cosmet Dermatol. 2023 Nov;22(11):2950-2956. doi: 10.1111/ jocd.15970. Epub 2023 Aug 26. PMID: 37632259.

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Figure 5 (A) Before and (B) after treatment. Red arrows indicate a displacement of 5 mm or more with the frontal region in maximum contraction. 30 days after treatment, a noticeable reduction of red arrows pointing to a cranial direction was found

Figure 6 (A) Before and (B) after treatment. There was no caudal displacement of the eyebrow at rest in the post-treatment period, and the eyelid opening remained unchanged

Figure 7 (A) Before and (B) after treatment. Upon contraction of the frontal muscle, an unaltered displacement of the eyebrow is observed, indicating that the frontal muscle maintains its activity