Mesotherapy, microneedling, and chemical peels are minimally invasive techniques used to combat facial aging. Chemical peeling is one of the oldest methods of facial rejuvenation. By using different chemicals in various combinations, strengths, and application techniques, plastic surgeons can tailor a patient’s treatment for optimal, safe, and consistent results. Mesotherapy and microneedling have emerged in the plastic surgery literature with increasingly complex indications. Both techniques have increased in popularity although research into efficacy and long-term results is lagging. With a thorough understanding of patients and the modalities available, plastic surgeons can use the appropriate minimally invasive technique to provide patients with desired skin changes.
Key points
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Mesotherapy, microneedling, and chemical peels are three minimally invasive techniques used today to combat facial aging.
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Chemical peels can be used in various combinations, strengths, and application techniques to optimize outcome while minimizing complications.
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Mesotherapy most commonly involves multiple injections of bioactive substances for facial contouring through lipolysis.
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Microneedling utilizes controlled needle penetration of the skin to stimulate the wound healing cascade and induce regeneration of skin components.
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A thorough understanding of the indications and limitations of these techniques will allow the plastic surgeon to maximize their patient’s outcome.
Introduction
Mesotherapy, microneedling, and chemical peels are 3 very different techniques used today for the common goal of facial rejuvenation. Mesotherapy, from the Greek words mesos (middle) and therapeia (to treat medically), uses multiple subcutaneous or intradermal injections of pharmaceutical and homeopathic medications, plant extracts, vitamins, and other bioactive substances into the dermis and/or subcutaneous fat. Proposed indications include vascular and lymphatic disorders, pain, alopecia, and psoriasis. Although first reported in the 1950s, mesotherapy has only recently gained popularity in the United States as a nonsurgical method of rejuvenation, particularly for fat reduction.
Microneedling, also known as percutaneous collagen induction (PCI) or collagen induction therapy, was first described in the 1990s as a novel method of skin resurfacing obviating laser ablation. Rather than the injection of substances used in mesotherapy, microneedling uses the physical trauma of needle penetration to promote regeneration. PCI does not ablate the epidermis nor create open wounds, thereby requiring little downtime and a shorter healing phase compared with ablative modalities, such as laser or dermabrasion. By leaving an intact stratum corneum and basement membrane, microneedling can be used on all skin types with reduced risk of photosensitivity, infection, and pigmentation changes.
In contrast to both mesotherapy and microneedling, chemical peeling is a topical modality in which application of chemicals creates injury to the skin. Purposeful injury to the epidermis and dermis stimulates growth and exfoliation to reverse skin degeneration from time, trauma, disease, ultraviolet, and environmental exposures. Its immense versatility comes from the number of chemicals available as well as the technique used. Chemical peeling is a tried-and-true procedure for skin resurfacing and rejuvenation used for thousands of years and continues to be a cornerstone in the treatment of facial aging.
Today, nonsurgical aesthetic procedures have become increasingly popular and varied from energy-based modalities to physical methods, including injectables, PCI, and chemical peeling. With appropriate understanding of various nonsurgical modalities for facial rejuvenation, plastic surgeons are able to better implement a treatment plant to maximize efficacy and minimize complications.
Introduction
Mesotherapy, microneedling, and chemical peels are 3 very different techniques used today for the common goal of facial rejuvenation. Mesotherapy, from the Greek words mesos (middle) and therapeia (to treat medically), uses multiple subcutaneous or intradermal injections of pharmaceutical and homeopathic medications, plant extracts, vitamins, and other bioactive substances into the dermis and/or subcutaneous fat. Proposed indications include vascular and lymphatic disorders, pain, alopecia, and psoriasis. Although first reported in the 1950s, mesotherapy has only recently gained popularity in the United States as a nonsurgical method of rejuvenation, particularly for fat reduction.
Microneedling, also known as percutaneous collagen induction (PCI) or collagen induction therapy, was first described in the 1990s as a novel method of skin resurfacing obviating laser ablation. Rather than the injection of substances used in mesotherapy, microneedling uses the physical trauma of needle penetration to promote regeneration. PCI does not ablate the epidermis nor create open wounds, thereby requiring little downtime and a shorter healing phase compared with ablative modalities, such as laser or dermabrasion. By leaving an intact stratum corneum and basement membrane, microneedling can be used on all skin types with reduced risk of photosensitivity, infection, and pigmentation changes.
In contrast to both mesotherapy and microneedling, chemical peeling is a topical modality in which application of chemicals creates injury to the skin. Purposeful injury to the epidermis and dermis stimulates growth and exfoliation to reverse skin degeneration from time, trauma, disease, ultraviolet, and environmental exposures. Its immense versatility comes from the number of chemicals available as well as the technique used. Chemical peeling is a tried-and-true procedure for skin resurfacing and rejuvenation used for thousands of years and continues to be a cornerstone in the treatment of facial aging.
Today, nonsurgical aesthetic procedures have become increasingly popular and varied from energy-based modalities to physical methods, including injectables, PCI, and chemical peeling. With appropriate understanding of various nonsurgical modalities for facial rejuvenation, plastic surgeons are able to better implement a treatment plant to maximize efficacy and minimize complications.
Mesotherapy
In the 1950s, Dr Michel Pistor injected intravenous procaine in an unsuccessful attempt to treat an acute asthma attack in a partially deaf patient. Although it was a failure as an asthmatic therapy, intravenous procaine injection temporarily restored hearing and the concept of mesotherapy was born. Since then, a variety of solutions have been used to treat a multitude of conditions. Although popular in Europe and South America, mesotherapy has met resistance in the United States due to a lack of clinical and scientific evidence. In 2005, no substantial clinical scientific studies on the workings of mesotherapy had been published. It was conjectured to work by increasing blood flow as well as lymphatic flow in the mesoderm, resulting in shrinkage of fat cells, which ultimately dissolve and are excreted. Comparatively, the past decade has shown significant advancements in the basic science research of mesotherapy and injection lipolysis, in particular.
Classic Mesotherapy
Injections of vitamins, minerals, homeopathic remedies, and proteins have been the mainstay of mesotherapy. The terms, mesolift and mesoglow , have been developed to describe the result of toning and facial rejuvenation with mesotherapy. Reduction of facial rhytids, increased elasticity, and improved pigmentation have been suggested but never proved. In a 2006 skin rejuvenation study, subjects receiving injections of a multivitamin mixed in hyaluronic acid (HA) demonstrated no significant changes in epidermal thickness, vessel size and density, solar elastosis, and elastin content. Electron microscopy revealed smaller collagen fibers, suggestive of new collagen synthesis, but at 6 months, no clinical change was appreciated. In a similar study, 6 patients underwent injections of a multivitamin solution mixed with a non–cross-linked, high-viscosity HA to the periocular region. Two subjects showed mild changes with increased glowing of the skin, but none reported improvement in skin tightening or wrinkles after 3 months. No difference was seen in epidermal thickness and an insignificant increase in type III collagen was seen, along with a decrease in total elastin.
HA is often chosen for mesotherapy due to its ability to increase hydration and fibroblast activation. HA stimulates fibroblasts to express collagen type I, matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of MMP-1 (TIMP-1). In 2011, Jager and colleagues used fibroblasts from skin biopsies maintained in 5 distinct formulas to help further elucidate molecular and cellular mechanisms. HA and various vitamin cocktails applied to human fibroblasts maintained cell proliferation and enhanced mRNA expression of collagen type I, MMP-1, and TIMP-1 for at least 11 days. Two other solutions, thought to work by stimulating repair mechanisms, led to proapoptotic processes and necrosis. Savoia and colleagues used 2 other HA formulations, 1 with vitamins, amino acids minerals, coenzymes and antioxidants, and the other with idebenone, and reported improved epidermal texture and increased elasticity and brightness of skin. Clinical evaluation with the Global Aesthetic Improvement Scale score and Wrinkle Severity Rating Scale revealed statistically significant results at 2 months although biopsies failed to show any significant difference at the level of the epithelium and of the dermis. Immunohistochemistry revealed a decrease in interleukin 1β, interleukin-6, and MMP-1 and increased collagen type I at 6 weeks after treatment.
Injection Lipolysis
Although HA is considered a key component in mesotherapy for facial rejuvenation, other agents are used when targeting unwanted adiposity for injection lipolysis. Since a 2001 report by Rittes described injecting phosphatidylcholine (PC) to improve lower eyelid bulging, numerous studies have contributed to the understanding of injection lipolysis with 2 agents: PC and deoxycholic acid (DC). DC acts as a detergent, disintegrating the fat cell membrane. This results in cellular oncosis, a process characterized by swelling and formation of blebs, resulting in increased permeability. Lysosomes eventually leak hydrolase, which damages the cell membrane, resulting in cell lysis. DC has been shown nonspecific in its toxic behavior, affecting adipocytes, skeletal muscle cells, keratinocytes and fibroblasts. It is thought that protein binding in nonadipose tissue may neutralize its effects to these other key structures. Furthermore, PC has been shown to have a buffering effect, leading to a reduction in inflammation and tissue damage. This is ideal for larger areas to be treated, such as hips and thighs. When treating the face or neck, however, isolated DC is most beneficial in focal areas, such as submental fullness.
Several companies have conducted clinical trials involving various lipolysis products. On April 29, 2015, the US Food and Drug Administration approved ATX-101 (Kybella) (Allergan, Irvine, CA) for improvement in the appearance of moderate to severe convexity or fullness associated with submental fat in adults. More than 20 clinical trials with more than 2600 patients were carried out by a global clinical development program. Phase I trials demonstrated that ATX-101 is relatively safe, with a transient increase of plasma DC, which normalizes after 24 hours. Adverse events included edema/swelling (87%), hematoma/bruising (72%), pain (70%), and numbness (66%). Two phase 3 trials where patients received ATX-101, 1 mg/cm 2 and 2 mg/cm 2 , or placebo, were conducted in Europe and their pooled results are as follows: 58.8% and 63.8%, of those receiving 1 mg/cm 2 and 2 mg/cm 2 , respectively, had improvements in clinician reported measures versus 28.6% in those receiving placebo. Treatment did not lead to worsening of skin laxity. Five cases of injection site nerve injury occurred and all spontaneously resolved. Similar results have been found in the US phase 3 trials, with 68.2% of patients having at least a 1-point increase in clinician-reported and patient-reported submental fat rating scales. The manufacturer recommends a maximum of 50 injections, 0.2 mL each (up to 10 mL), spaced 1 cm apart. Using this method, up to 6 single treatments may be administered at intervals no less than 1 month apart. Another agent undergoing clinical trial is salmeterol xinafoate (Lipo-202) (Neothetics, San Diego, CA). This injectable formulation of a long-acting ß 2 -adrenergic receptor agonist may achieve lipolysis by triggering the metabolism of triglycerides stored in the fat cells and causing shrinkage. It is used specifically for abdominal bulging, but given its different mechanism of action, there are theoretically fewer side effects and less inflammation. An upcoming agent, Aqualyx (Marllor International, Marignano, Italy) is a DC-based solution with a lactose-based delivery system. It has received the European Conformity mark for localized fat reduction, and shows promising and significant results in multiple areas of the body when performed by fully trained practitioners.
Complications
Although mesotherapy is relatively new in the literature, complications have been reported, with infection the most commonly reported. More than 198 separate cases of associated infections have been documented, all of which were caused by atypical mycobacteria. Late consequences of injecting DC include necrobiosis of the reticular dermis and death of adnexal glands, blood vessels, and nerves in the deep dermal layer. Most mesotherapy patients experience minor side effects postinjection, including erythema, edema, and ecchymosis. Despite this, patient satisfaction has been reported at more than 85% for those receiving treatment in the orbital fat compartments, neck, submental, and jowl fat areas.
Microneedling
In contrast to mesotherapy, microneedling uses direct mechanical trauma to modify tissues. Traditional ablative techniques injure tissue beyond the epidermal-dermal junction, effectively disrupting the basement membrane and causing fibroblast deposition of collagen in a parallel orientation inherent in visible scars. PCI is believed to induce more regenerative effects by inducing the normal wound healing cascade of inflammation, proliferation, and remodeling within normal skin architecture. Microneedling devices applied to the skin create a controlled depth of microchannels, which close within minutes, during which time topical substances can be delivered and captured. Shortly after the microneedles penetrate the skin, platelets release chemotactic factors causing invasion of other platelets, neutrophils, and fibroblasts. The neutrophils are replaced and monocytes change into macrophages within the first 48 hours. Macrophages release numerous growth factors, including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and transforming growth factor (TGF)-α and TGF-β, which stimulate the migration and proliferation of fibroblasts. In particular TGF-β1, TGF-β2, and TGF-β3 are involved in promoting scar collagen production and regeneration of normal collagen lattice structure and scarless healing. Keratinocyte-fibroblast interactions enhance the production of laminin and collagen types IV and VII at the level of an intact basement membrane. In the final stage of remodeling, fibroblasts continue to form and break down collagen in the upper dermis. Patients undergoing PCI can, therefore, expect continued improvement in overall skin quality, thickness, and obliteration of superficial wrinkles over several months in contrast to the more dramatic short-term results achieved by ablative laser resurfacing. Histologically, hematoxylin-eosin studies of treated skin have shown a significant increase in collagen deposition at 6 months as well as a 40% increase of the epidermis and normal rete ridges at 1 year after treatment ( Fig. 1 ).
In addition to dermal rejuvenation, PCI has been reported as a successful treatment modality for several skin conditions. Patients with postacne atrophic scars were shown to have increased collagen types I, III, and VII, resulting in significant improvement of scar appearance, skin tightness, and overall skin texture after 2 to 6 sessions of PCI over 1 to 3 months ( Fig. 2 ). Hair density in patients with androgenic alopecia and alopecia areata were also increased, presumably from increased vascularization and follicular and fibroblastic activity through multiple growth factors, including vascular endothelial growth factor, PDGF, and FGF-7. There is also potential to help patients with stretch marks by increasing elastin fiber density with microneedling treatments and theoretically reducing the striae gap distance to improve overall appearance. In the rat model, by pretreating skin with microneedling, subsequent fat grafts placed in those areas had greater integrity, vascularity, and overall survival compared with controls.
More recently, microneedling technology has been augmented with additional modalities. Bipolar radiofrequency devices have been used to treat acne vulgaris and oily skin by inhibition of sebaceous gland through heat production; however, the distance between electrodes limits the penetration of standard bipolar radiofrequency. Fractionated radiofrequency microneedling overcomes this limitation by applying direct thermal injury to the dermis between paired microneedles to precisely administer bipolar radiofrequency at specific depths. This has resulted in overall clinical improvement of acne scar and acne vulgaris and related erythema. When used in conjunction with platelet-rich plasma, PCI increased survival rates in skin flaps created in rat models.
Equipment
There is a significant range of equipment available for PCI techniques. Standard tattoo devices require accurate control of depth by the user at all times and are, therefore, unlikely to provide a consistent depth of needling for larger areas. Stamp devices allow spot treatment of smaller areas and localized scars. Electronic stamp devices allow the user to select both penetration speed and needle depth, decreasing patient discomfort and allowing the same instrument to be used on various areas of skin. Tip cartridges on stamping devices are disposable. Drum-shaped rollers have great variation in needle material (gold, titanium, and so forth), length, diameter, and overall surface density, depending on the manufacturer. Rollers are 1-time-use devices best for open flat surfaces, such as the cheek, but are more challenging in narrow channels, such as the perioral or scalp area, where hair can become entangled. Medical needle depths range from 0.5 mm to 3 mm although home-care devices with needles less than 0.3 mm are available for self-treatment. In addition to varied design styles, features, such as vibration, light-emitting diodes, and radiofrequency, are dependent on the manufacturer. Regardless of the type of equipment, a quality build is essential for minimal risk of needle breakage into the skin, ease of use, and maximum results.
Technique
Prior to treatment, patients should avoid prolonged sun exposure or sunburns for at least 24 hours to avoid excessive inflammation and injury. Topical products are discontinued 12 hours prior and the skin must be clean and free from cosmetic products. Any patient with active or resolving infection should have treatment delayed until resolution.
When preparing a patient, the skin is first cleaned with a gentle cleanser with or without exfoliation. Topical anesthetic is applied and left on the skin for 20 minutes prior to removal with rubbing alcohol. Areas that are sensitive or require aggressive treatment, such as the upper lip, may benefit from local nerve blocks. A topical hyaluronic-based gel is then layered on the skin as a lubricant, with the added benefit of being an active ingredient that is microinjected into the skin through microneedling action. Depending on the device used, appropriate needle length and speed are chosen for the planned treatment area. Areas of thin skin overlying bony surfaces, such as the forehead, nasal, periocular, and upper lip area, require shorter needle lengths ranging from 0.25 mm to 0.5 mm. Patients with thicker skin or scarring can tolerate deeper needle lengths from 0.5 mm to 2 mm. Areas of thick skin, such as the face, chest, and trunk or with significant scarring, can be treated with depths up to 2.5 mm. Increasing speeds are used with longer needle lengths to help minimize discomfort. The method of needle application is user-dependent with the common endpoint of mild swelling, evenly spread erythema, and transient punctate bleeding ( Fig. 3 ). This is achieved by applying appropriate pressure, speed, and needle depth for the skin quality and thickness of the area being treated. Multiple passes over the same area in different vectors are recommended to avoid track marks from repeat needle insertions into the same microchannel. This creates unintentionally larger wounds and undesirable cicatricial healing. On completion, the skin is washed with sterile water to remove residual serum and debris. At this point, transdermal delivery of substances, such as topical vitamins, peptides, growth factors, and other active ingredients, can be immediately applied while microchannels are still patent. An additional layer of petrolatum-based skin protectant can be applied. Multiple sessions are spaced at 1-month intervals to allow sufficient epidermal and dermal proliferation and to achieve the desired clinical effect. Other techniques, such as subcision or punch elevation, may be combined for optimal results for difficult skin conditions, such as deep acne scars.
Postprocedural Care
There may be the feeling of a sunburn-like discomfort for the first few hours post-treatment that can be treated with over-the-counter analgesics or an HA-based hydrating serum. Sunscreen and cosmetic products are to be avoided for at least 12 hours. The patient can return to work the next day although swelling may persist into the second or third day. Erythema and mild desquamation can last up to 5 days after which regular skin care, including tretinoin, can be restarted. By 1 week, patients can expect to be free of postprocedural side effects although they should avoid any alcohol, acid-based toners, and direct sun exposure for 2 weeks. Antiviral medication is indicated to prevent herpes simplex outbreak.
Complications
There are a few reports of complications in the microneedling literature given its minimally invasive, superficial mechanism of action. Multiple treatment sessions using a 1.5-mm needle depth have shown to initiate collagen synthesis with no interference of the patient normal lifestyle. Increasing needle depth to greater depths (up to 3 mm) has demonstrated improved results but with longer downtime and greater swelling, bruising, and bleeding. Careful cleansing and preparation of the skin is important to avoid introducing immunogenic particles into the dermis, which may initiate local or systemic hypersensitivity reactions. Soltani-Arabshahi and colleagues described 3 cases of foreign body–type facial granuloma formation due to intradermal tattooing of topical moisturizer during microneedle therapy. Two of these patients also had positive patch test reactions to vitamin C serum. Steroid therapy was ineffective with only partial improvement after doxycycline hydrochloride and minocycline hydrochloride treatment. In a case report by Pahwa and colleagues, a female patient formed tram track scars; multiple lines of pigmented punctate hypertrophic scars were formed in the direction of microneedle roller application predominantly over the bony prominences of the zygoma, forehead, and temporal area. Slight improvement occurred after topical silicone gel treatment. Special considerations should be given to patients with a history of keloid or hypertrophic formation, particularly if treatment is planned over bony prominences. In these patients, setting a more superficial needle depth and avoiding repetitive passes over the same areas can reduce trauma.
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