Improving skin texture in the face is a popular procedure in older women. Procedures using stabilized hyaluronic acid (S-HA) to improve skin texture should be distinguished from volumizing procedures.1 The intradermal injection of S-HA has many benefits, such as being safe from embolism, being easy to inject, and leading to dramatic improvements in skin texture and hydration.2 HA is the main component of the extracellular matrix (ECM) and dermal hydration can help counteract the effects of aging. When the dermis is well hydrated using S-HA, it looks healthier, and this effect can last for more than half a year.1,2 Various intradermal injection techniques have been reported, such as manual injection,3 the blanching technique,4 and automatic injector using multiple needles.2 The dermis can be treated with microdroplets (0.001 cc) of S-HA at a thousand of injection sites using an automatic injector. This unique injection method was named “Microhyaluronicacid” by the author, based on an analogy with Microbotox.5 Microhyaluronicacid and Microbotox were combined by the author. The author invented a unique injection solution in which S-HA is mixed with botulinum toxin A; this solution has been used for dermal hydration and skin rejuvenation since 2009.1,2 To reduce the risk of creating a dermal lump, polydensified monophasic HA and automatic injector were used. In 50 patients, changes in fine wrinkles were measured using a dermascope, and dermal hydration was measured by transepidermal water loss (TEWL) and stratum corneum hydration (SCH) levels.
PATIENTS AND METHODS
The study was a single-center, prospective, in vivo study with dermal injections using a unique mixture of S-HA and botulinum toxin A. From January 2014 to December 2016, 50 women (age range, 31–65 years; average age, 49.8 years) with fine wrinkles and subjective signs of dryness on the face (especially forehead, around the eyelid, and the upper lip) participated in the study. All subjects had been treated with only botulinum toxin in the past (more than 6 months ago) at the author’s clinic and were familiar with the injection processes associated with Microbotox.5 The intradermal injection method of S-HA using an injector (Microhyaluronicacid) was already approved by the Korean Intellectual Property Office as a patented technology.6 Informed consent was obtained from each patient about Microhyaluronicacid and Microbotox, and the study adhered to the tenets of the Declaration of Helsinki. All patients received intradermal injections and were observed to assess (1) changes in the appearance of the facial skin; (2) changes in dermatoscopic findings; and (3) SCH and TEWL values. Subjects were to adhere to their usual skin care routine for 8 weeks before and 6 months after the injections. The subjects who had procedures such as HIFU (Unthera) or RF (Thermage) within 1 year before and after the injection were excluded.
Before the treatment, patients were first prepared with a layer of 9% lidocaine topical anesthetic cream and covered with plastic wrap as occlusive draping to facilitate the infiltration of anesthetic materials into the dermis. After 30 minutes, this was thoroughly washed off.
For reconstitution of the injection material, 1 cc of polydensified monophasic HA (Belotero Balance; Anteis, Geneva, Switzerland, and distributed by Merz Pharmaceuticals) was mixed with 1 cc (40 U) of incobotulinum toxin A (Xeomin, Merz Pharmaceuticals, Germany) and 1 cc of normal saline. This mixture of Belotero and Xeomin was named the “XeoBel hydrotoxin” solution and can be used in a single session for Microbotox and Microhyaluronicacid procedures. During the reconstitution, it is very important to ensure that no air bubbles are present in a 3-cc syringe without forming air bubbles passing 30 times through connector and two 3-cc syringes, because air bubbles collapse with the pressure of the injection and can disturb or delay the injection. In this procedure, 3 cc of the XeoBel mixture was injected in 990 sites on the face. Therefore, the amount of toxin was approximately 0.04 U, and the amount of S-HA was 0.001 cc per injection site. An automatic injector (XeoBel-injector; Contac-Korea, Seoul, Korea) was used to inject the solution into the dermis. The injector ensured the depth was intradermis with 0.001 c of amount for all patients. The depth of the injector was set at 1 mm, and the actual injection depth was approximately 0.8 mm due to bevel on the needle tip.5 This device has nine 32-gauge needles, which were distributed in a way that provided a regular distance (3.5 mm) between the injections of Microbotox and Microhyaluronicacid throughout the face (see video, Supplementary Digital Content 1, which displays the injection method that does not create lumps after injecting S-HA to the dermis: which includes (1) monophasic HA; (2) lessened injection amount per site; and (3) dilution. This video is available in the “Related Videos” section of the Full-Text article at PRSGlobalOpen.com or at http://links.lww.com/PRSGO/A861).
If the solution is too easily injected and a leaking sound can be heard, the needle has most likely been inserted too superficially. If a leaking sound occurred, the injection depth was increased by 0.2 mm.5 Whereas more bleeding means that the injection depth is too deep under the dermis. If substantial bleeding was noted, the injection was considered to have penetrated the subdermal plexus. With good injection technique and optimal injection depth into the dermis, there is less bleeding and ecchymosis and the possibility of injecting too much in a single location diminished. Very small raised lumps or blanched blebs in the skin should be seen after an intradermal injection (Fig. 1), and these are normal due to the depth of the injection. These lumps disappeared the following day. To reduce dermal lumps, polydensified HA was used because it has a high spreading property and it can integrate with the skin.7
At the end of the procedure, ice cooling and compression were applied on the face to relieve pain and to facilitate in the spread of dermal lumps. Thin skin, such as the lower eyelid, lumps can easily develop, and these lumps should immediately be spread out by compression with a cotton ball or massage (see video, Supplementary Digital Content 1).
Skin Roughness and Morphology
Skin roughness and morphology were evaluated using 5 levels (1: very smooth, 2: smooth, 3: moderate, 4: rough, and 5: very rough) at 2, 4, and 8 weeks using a noncontact method with a dermatoscope (×10, ×50 resolution, Coscam, Sometech, Korea) on the forehead (2 cm above the right eyebrow on the vertical pupil line) and crow’s feet area (2 cm lateral to and 2 cm below the right lateral canthus).
Measurement of Biophysical Parameters (SCH, TEWL) for Dermal Hydration
Before the biophysical measurements were obtained, patients did not use moisturizers at the measurement day and washed their face with the same cleanser in clinic 30 minutes before the measurements. The patients remained in a comfortable emotional state for 30 minutes at room temperature before taking the measurements to avoid confounding factors. Hydration of the dermis was measured using a noninvasive instrument (gpskin-barrier; gpower, Seoul, Korea). Gpskin simultaneously scans the TEWL and SCH levels of the skin. TEWL and SCH were measured on the forehead and crow’s feet area (same areas of dermascope) at 2, 4, and 8 weeks.
Histologic Study of Injected Hyaluronic Acid
Three subjects (38-, 41-, and 45-year-old women) also agreed to allow individual studies with different materials on each side of the face and biopsy samples from the face to be taken on the 28th day after implantation during planned face lifting on the temple area. Polydensified HA was injected on the left side of the face, and biphasic HA (Restylane Vital; Galderma, Uppsala, Sweden) on the right side of the face. The purposes of the biopsy study were (1) to confirm the depth of the deep dermis and to investigate whether an injection technique using an automatic injector for intradermal injection would be successful in terms of providing an even distribution in the deep dermis of the face and (2) to compare the histologic distribution and various features of the collagen fibers displaced by the HA gels after the intradermal injection of polydensified HA and biphasic HA.
Many small lumps were observed in close-up photographs and on dermatoscope at the 990 injection sites immediately after using 3 cc of the XeoBel mixture (Fig. 1), although these lumps disappeared after 1 or 2 days. Microbotox did not disturb facial expressions, and Microhyaluronicacid spread well and did not result in visible lumps. Microbotox and Microhyaluronicacid created vast improvements in fine wrinkles such as the crow’s feet and forehead areas (Figs. 2–5) (see figure, Supplementary Digital Content 2, which displays the microscopic view; the effect of “Hydrotoxin method” is extraordinary: healthy and smooth skin, improved fine wrinkles, http://links.lww.com/PRSGO/A862).
Clinically apparent improvements after 1 session lasted for 6 months in most cases according to measurements of SCH. Subjective improvements in dryness after face-washing were also reported by patients 1 or 2 weeks after the injections, while SCH increased immediately. It may take some time for the material to diffuse into the ECM from the injection site, causing improved feelings of dermal hydration.8
Ecchymosis was found after the injections; generally, it lasted for approximately 3 days, although it lasted for 7 days or more in 7 patients (14%) who had thin skin. Thirteen patients (26%) who had relatively thick skin did not suffer from ecchymosis. Ecchymosis could have been due to injections into the subdermis, and this can easily occur when patients have thin skin. The likelihood of subdermal injections was therefore greater in patients with thin skin. However, the improvement of fine wrinkles was greater in patients with thin skin than those with thicker skin. The combination of Microbotox and Microhyaluronicacid was safe from infection, allergy, itching, and inflammation on physical examinations and histologic study.
On microscopic views, skin roughness improved from 3.9 to 1.8 on the forehead and lateral canthus. Fine wrinkles and roughness dramatically improved in the face after the procedure, especially in the crow’s feet and forehead areas (Figs. 3–5). All patients experienced improvement of skin roughness after 2, 4, and 8 weeks.
TEWL and SCH
TEWL sensor measures how much water the skin loses. A strong skin barrier keeps moisture in the skin, and a weak barrier does not hold moisture well. The SCH sensor measures how much moisture the skin is holding. TEWL and SCH on the forehead and crow’s feet improved (Fig. 6). TEWL and SCH after treatment showed that the barrier function of the skin became stronger, meaning that skin was retaining more moisture. According to the patients, dryness after face-washing improved, and patients felt less dryness of the skin. The changes between TEWL and SCH on forehead and crow’s feet were of statistical significance (paired t test < 0.05) at 4 and 8 weeks (Table 1).
Histologic Study of the Injected Hyaluronic Acid in Dermis
- (1) With a 1-mm depth setting on the automatic injector, the actual injection depth on the face was approximately 0.5–0.9 mm because of the bevel of the needle tip.
- (2) On the biopsy study, the polydensified HA was placed with minimal displacement of collagen fibers within the dermis, showing infiltration between collagen fibers. In contrast, the microdroplets of biphasic HA were placed with displacement of collagen fibers within the dermis, showing dermal volumizing effect.
- (3) Dermal thickness was measured from the epidermis to skin appendages. Dermal thickness increased more on the right side of the face, which was injected with biphasic HA, than on the left side.
- (4) There were no inflammatory cells (macrophage, eosinophil, mast cell, plasma cell, and giant cell) around the S-HA on both sides, with polydensified HA (Belotero Balance) on the left side of the face and biphasic HA (Restylane Vital) on the right side of the face (Fig. 7).
In manual injections of Microbotox, the injections are delivered into the dermis using insulin syringe with a 30-G needle, raising a tiny blanched wheal at each point, with efforts made to create wheals of the same size/diameter on the dermis. Microbotox refers to the injection of multiple microdroplets of diluted botulinum toxin A into the dermis for skin rejuvenation.5 Microbotox can be used to decrease sweat and sebaceous gland activity and to improve skin texture, such as fine wrinkles, or in Nefertiti lifting. For treatment of the lower face and neck fold, microdroplets of botulinum toxin improve skin texture, smoothen horizontal creases, and decrease vertical banding of the neck; these effects may be caused by a specific mechanism in the dermis and through paralysis of the platysma muscle.5 Microbotox is used to treat various parts of the face (forehead, glabella, the crow’s feet area, the infraorbital area, and cheeks) and neck.5 The Microbotox technique is easy to learn and administer, with fewer side effects and no unwanted muscle effects.
HA is the main component of the ECM. Intradermal injection of HA has many benefits, such as being safe from embolism, being easy to inject, and leading to more dramatic results on the superficial dermis. A well-hydrated dermis looks healthier, and dermal hydration can help counteract aging of the skin1,2; injection of S-HA can be used to hydrate the dermis at the same time. As we age, the amount of HA associated with collagen and elastin decreases slowly, and the use of realistic replacement ingredients to remediate dermal deficiencies in a safe manner is the goal of HA treatments in most clinics.9
With increasing aspirations to treat the skin surface and to rejuvenate the dermis, advancements in hyaluronic acid technology have led to the introduction of new dermal fillers for injection into the dermis, such as Restylane Vital, Belotero Balance, Neuramis light, and Y-solution 360. For intradermal injections, less reticulated gels with lower concentrations of HA or small-particle HA are often intended to treat fine wrinkles or thin-skin areas such as crow’s feet, vertical wrinkles on the upper lip, and the horizontal neck fold. Belotero Balance is produced by 2 cycles of cross-linking with butanediol diglycidyl ether (BDDE), and results in zones of greater and lesser density inside the filler gel.10,11 Unlike other S-HA fillers for which the intradermal plane is suggested, a new form of S-HA with a polydensified monophasic HA gel may be more appropriate for the superficial dermis, because it has a high degree of spreading with lower viscosity, cohesiveness, and elasticity. These properties of S-HA may promote more extensive integration with the dermis, creating more plasticity and reducing the chance of lumps developing in the dermal layer, which is composed of high-density collagen and elastic fibers (Fig. 7). However, these properties have a disadvantage, in that when Belotero Balance is injected into the dermis, it appears to spread inside the dermis and migrate into the subdermis, also without forming nodules or clumps.12 Therefore, the spreading property of Belotero Balance resulting in less longevity than biphasic HA.12 Although biphasic HA has greater longevity after intradermal injections, the likelihood of creating lumps may also be greater.2 There is no currently available filler with a high degree of spreading and longevity.
Various intradermal injections have been reported, one of the most common methods being the blanching techniques.2–4 To inject HA into the superficial dermis, the blanching technique was presented by European physicians13 in 2011. It has been mentioned in recent articles in the clinical literature,10 and has been deployed in many clinics over several years, with no consequential adverse events.4 With this technique, blanching is caused both by vasoconstriction by to the proximity of the transparent gel to the skin’s surface; other reasons for blanching techniques success could include tissue distention and blood displacement.4,10 To achieve blanching, the amount injected into a single site is too much and causes a lump, which, combined with the above-mentioned reason reduces the appearance of wrinkles. Blanching means that the injection was into the intradermis, and it is a good indication of depth, but it is a less ideal injection method for dermal hydration than automatic injection with microdroplets because of uneven distribution that makes blanching.
When a physician injects S-HA and botulinum toxin separately, it takes more time and is tiresome. Since 2009, when the author’s technique was first developed, the author has treated over 2,000 patients with the hydrotoxin method1,2 and the author has obtained a patent from the Korean Intellectual Property Office6 (see figure, Supplementary Digital Content 3, which displays the newspaper from Money Today. My method that we address in this article is a trend in Korea. In the left-bottom picture, Dr. Fravert (developer of Xeomin) visited our hospital to congratulate on the development of XeoBel method, http://links.lww.com/PRSGO/A863; see figure, Supplementary Digital Content 4, which displays the patent from the Korean Intellectual Property Office. The author has treated over 2,000 patients with the hydrotoxin method, http://links.lww.com/PRSGO/A864).
With an automatic injector and the XeoBel mixture, patients felt less pain and the procedure took less time. It was like “killing two birds with one stone.” The XeoBel mixture has been used in more than 300 patients in the author’s clinic to improve fine wrinkles and dermal hydration. The author’s unique combining method of Microbotox and Microhyaluronicacid at 990 injection sites did not result in visible lumps (lumps disappeared when treated by cold compression and the spreading property of HA); it was safe from vascular problems, infection, irritation, and inflammation.
- (1) The combination of Microbotox (0.04 U) and Microhyaluronicacid (0.001 cc) injected in 990 sites did not create visible lumps and disturb facial expression, and the procedure was very safe from vascular problems and inflammation, confirming it to be a safe method. In histologic study, there were no inflammation cell around S-HA.
- (2) Fine wrinkles on the crow’s feet and forehead areas improved after the procedure.
- (3) TEWL and SCH improved after the treatment; the skin became hydrated and healthier with a strong barrier with statical significance at 4 and 8 weeks.
- (4) With the automatic injector, the actual injection depth on the face was found to range from 0.5 to 0.9 mm in the dermal layer. By using an injector, the time for the procedure involving 990 injection sites can be reduced.
The author expresses his thanks to his Mother (Shin, Choon-Ja) and his hopes for her to get well, with full recovery from lung cancer.
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6. Title of invention: injection technique using S-HA and automatic injector for dermal hydration and rejuvenation. Patent number: 10-1790405, Certificate of patent of Korean intellectual property office.
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Copyright © 2018 The Author. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.