New trends in face rejuvenation by hyaluronic acid injections


Paris-Université Laser Skin Clinic, 157 rue de l’Université, 75007 Paris, France, E-mail:


Background  Injection techniques are growing, thanks to safer and more suitable filling agents. Hyaluronic acid (HA), a biodegradable product, has become the “gold standard” for fillers. With its wide range, it not only improves wrinkles but also restores volume.

Methods  Since 1996, many patients have been injected for wrinkles, fine lines, and nasolabial folds. For 3 years, more viscous HAs have been launched, allowing us to restore volumes. Some new procedures are described. These can correct anomalies of the chin and of the nose, and allow a betterment of the periocular area by correcting hollow and falling eyebrows.

Results  The use of different HAs for each area and indication is suitable and offers real possibilities to rejuvenate the skin without downtime. Longevity of the correction depends on treated areas, HA used, and on the individual.

Conclusion  HAs are safe and suitable for wrinkles and volume restoration, but besides their mechanical properties, they have numerous physiological functions. With the analysis of literature about the action mechanism of HA and its receptors, it is evident that HA also has a stimulating action on different physiological process.


The world's population is aging, and aesthetic demands from patients are increasing. Looking young and feeling fit is considered the norm in all industrialized countries. Surgical techniques were the first ones considered in the past for rejuvenation.

To date, aesthetic dermatology has evolved enormously with the arrival of many new, noninvasive, outpatient techniques that help to improve appearance. Filling agents have become more and more efficient and safe.

Although wrinkle filling remains one of the main indications, the restoration of volumes and contours and the creation of a balanced, natural look must also be taken into account when treating the aging face today.

Apart from signs of aging, some new techniques of correction permit to enhance chin/nose deformities. For aesthetic indications, it is always suitable to choose biodegradable products, because any complications that could arise from these products will resolve themselves most often spontaneously.1

Hyaluronic acid (HA) is, at the moment, the “gold standard” of fillers.2 The range of HAs launched on the market may present some differences in terms of viscosity and duration; however, the safety standards are very high (Tables 1 and 2).

Table 1.   Restylane products (Q-Medical AB, Sweden).
  1. Biphasic product made of beads of different sizes. NASHA, non-animal-stabilized hyaluronic acid (20 mg/mL); VRF, volume restoration factor.

Restylane VitalNASHA1.0 mL Fluid gel
Restylane TouchNASHA0.5 mL500 000 gel particles/mLParticles size, 150 µm
RestylaneNASHA0.5 mL, 1 mL100 000250
Restylane LippNASHA0.5 mL, 1 mL  
Restylane PerlaneNASHA0.5 mL, 1 mL10 0001000
Restylane Sub-QNASHA2.0 mL10002000
Macrolane VRF 20 VRF 30NASHA10 mL, 20 mL  
Table 2.  Corneal-Allergan products.
  1. Monophasic products made of linear hyaluronic acids without beads.

Juvelift1 mL, 13.5 mg/mLMesotherapy
Juvéderm 180.6 mL, 18 mg/mLFine lines
Juvéderm 24 HV0.8 mL, 24 mg/mLWrinkles, folds, lips
Hydrafill Soft Line
Juvéderm Ultra (USA)
Juvéderm 30HV0.8 mL, 24 mg/mLDeep wrinkles, folds, lips, volume augmentation
Hydrafill soft line max
Juvéderm Ultra Plus (USA)
Surgilift Plus1 mL, 13.5 mg/mLMesotherapy
Surgilips0.8 mL, 20 mg/mLLip augmentation
Surgiderm 24 XP0.8 mL, 24 mg/mLWrinkles, folds, lips
Surgiderm 30 XP0.8 mL, 24 mg/mLDeep wrinkles, folds, lips, volume augmentation
Juvéderm Ultra 20.55 mL, 24 mg/mLFine lines, lips
Juvéderm Ultra 30.55 mL, 24 mg/mLWrinkles, folds, lips
Juvéderm Ultra 40.8 mL, 24 mg/mLDeep wrinkles, folds, lips, volume augmentation
Voluma2 mL, 20 mg/mLFolds, volume augmentation


In 1996, HA was launched to the European market. From this point on, HA has become the “gold standard” in fillers, and millions of syringes have been injected for treating wrinkles and hydrating skin, as well as for increasing volumes.2–4

During this period, we used essentially HAs from two different companies: Restylane®, Perlane® (FDA approved), and Sub-Q® (not FDA approved) from Q-Med AB (Uppsala, Sweden), made of beads of HA of different sizes, realizing a biphasic HA (beads of HA within homogeneous HA) (NASHA technology); and Juvéderm® Ultra and Ultra Plus (FDA approved), Surgiderm® (not FDA approved), and Voluma® (not FDA approved) from Corneal-Allergan (Irvine, CA, USA), made of cross-linked HA in a monophasic state (no beads, but only homogeneous HA).

During the early years of HAs patients were treated only for wrinkles, nasolabial folds, and lip augmentation, but, progressively, we combined restoration of volumes and correction of small anomalies of the nose and of the chin.

A questionnaire was prepared for each patient about general medical conditions (autoimmune diseases, allergic past, etc.), and we asked the patients to discontinue any medications that could interfere with clotting tests (if possible), for their safety.

On average, we did not use any anesthesia, except for the perioral area where nerve block is easy to perform. For a few months, we injected Juvéderm Ultra 2, 3, or 4 (a mixture of different stabilized HA and of 0.3% lidocaine launched in the European market by Corneal-Allergan). These products are very effective and allow almost painless injections.

Injections of viscous and long-lasting HAs require a suitable canula or a needle. Blunt canula is safer than needle, but needle is more precise as the sharp bevel permits to place product exactly where we want it to be.

Voluma may be injected through a 21-G green needle or a canula, but Sub-Q requires a thicker needle or an 18-G canula. When using a canula, we perform anesthesia of the entry hole, but with a needle, pinching the skin when injecting avoids the use of anesthesia. Anyway, it is better to avoid any distortion (by infiltration) of areas that we want to enhance.

These products are injected deeply into the hypodermis, muscles, or over bony surface. Injection is better done withdrawing the needle (do not inject into a vessel).

At the end of the procedure, hand massage is useful to perfectly place the product. Pushing the entry areas avoids bleeding and sutures. No dressing is necessary but a plastic waterproof spray is useful.

The upper face

The forehead requires overall botulinum toxin (BT) to correct dynamic lines. The glabelar area, in case of deep furrows, is better treated with an association of BT (into corrugator and procerus muscles) and HA. HA injections in the best scenario are performed 1–2 weeks after BT injections (Botox® 20 U, Dysport® 70 U). As has been reported, one must be prudent when injecting in the glabelar area to avoid intravascular injection and the risk of necrosis.5

With aging, the temples may become hollow: a fanning technique of injection with HA gives good results (in this area, we like to inject Voluma through a canula with an entry in the scalp).

Small dynamic lines of the crow's feet are best improved by filling them with a fluid HA injected very superficially, and BT injections (Botox 15 U, Dysport 50 U into orbicularis oculi muscle).

Correction of the hollows and tear trough was made with Restylane, Juvéderm 24 HP, then Surgiderm 24 XP. These HAs have a suitable viscosity (especially for hollows) and permit a nice correction (Figs 1 and 2), with deep injections over bony surface. In the event of a too superficial injection, a lumpy surface forms with a bluish aspect due to Tyndall effect. In this area, gentle massage (not crushing!) is necessary. As HA is a hydrophilic agent, some swelling may occur during the next day in the hollows, and it is better to undercorrect than to overcorrect. For the lower part of the tear trough, Perlane, Juvéderm 30 HV, Surgiderm 30 XP or now Juvéderm Ultra 4 may be injected because the skin here is thicker.

Figure 1.

Filling of tear trough and increasing of volume of the cheek bones.

Figure 2.

Same technique as Figure 1.

When injecting tear trough, most of the time, we need also to increase volume of the cheekbones. Deep injections adjacent to bone are suitable. Under the superoexternal part of the cheekbone, there is a venous plexus that must be avoided by injecting deeply. Pushing is very important for avoiding bruising. In the case of a great loss of volume of the cheekbones, it is better to use more viscous products, such as Voluma or Sub-Q (Fig. 3). They permit a better volume augmentation with a greater longevity. These areas need expertise before filling it, and remember that it is better to undercorrect than to overcorrect.

Figure 3.

Cheek bones augmentation with Voluma (Corneal-Allergen), 18 months later.

In cases of overcorrection, hyaluronidase injections are very efficient.5 At present, we use only animal-derived product, which needs skin testing for detecting allergic reactions. In the near future, we will use recombinant human hyaluronidase, which is a hundred-fold less reactive.

Correction of falling eyebrows is quite an effective technique for rejuvenation. Face lift is the main surgical indication, but patients often only have a falling eyebrow with heavy upper eyelid. To keep a very natural look and just to open the eyes, fat-grafting or HA injections with viscous products (Voluma, Sub-Q, because of longevity) are a real alternative (Figs 4 and 5).6 We prefer Voluma because it is the easiest to incorporate on site over a bony surface compared to Sub-Q beads.

Figure 4.

Remodeling of eyebrows.

Figure 5.

Enhancement of the “look.”

The procedure consists of two sessions. The first one is performed under local anesthesia (troncular supratrochlear/supraorbital): one syringe of 2 mL of Voluma is injected on both sides under the whole surface of the eyebrows. Massage is important to well place the product. The next day, swelling appears and, sometimes, bruising. The second session is performed, if necessary, 2 weeks later. Final placement is 1 month after the last session, and duration of the improvement is more than 1 year for a “good clinical correction” (50% of persistent correction). Except for burning sensation and lumps, which will disappear progressively, the only drawback is bad placement of the product. The combination of these two techniques around the eyes permits a great natural enhancement of the eye zone.

The nose

Hyaluronic acid is easily injected into the nasal ridge to correct small defects (Figs 6 and 7). Fluid HA can be injected through a thin 30 G needle with no anesthesia needed. Enhancement is immediate and lasts a long time, depending on the injected HA (after Juvéderm 24 HV or Surgiderm 24 XP injections, a touch up 10–12 months later is sufficient).

Figure 6.

Nose correction.

Figure 7.

Nose correction.

In some cases, you can combine this treatment with BT injection into the depressor septi nasi (5 U Botox, 15 U Dysport) to raise the tip of the nose. This technique also permits without risk correction of postrhinoplasty defects.

The lower face

Nasolabial folds filling procedure is well known; it can be done either by multipunctures or threading technique. HAs of different viscosity are used.

Filling fine lines around the mouth (upper/lower lip) is not the best technique for this area, but it may bring some improvement for patients who do not want to undergo resurfacing. In this area, Juvéderm Ultra 3 or 4 permits almost painless injections, and in cases of dynamic lines, BT injections may be combined (1–2 U Botox into fine lines).

Marionette lines are easily filled, but correction is sometimes better in association with BT injections (into depressor anguli oris muscles), which raise the corners of the mouth (5 U Botox, 15 U Dysport).

Lip augmentation is also a “classical” indication and gives marvelous results if the physician has good expertise. In this area, swelling and bruising are more frequent than elsewhere and the procedure is painful without anesthesia. Injections may be done into the vermillion border and/or into the red part. Longevity of HA is less important here than in other areas. Restylane lipp and Surgilips are quite suitable.

Hollow cheeks are best filled with more viscous HAs (Voluma, Sub-Q).

Remodeling of the chin and, particularly, the lateral parts, which become hollow with aging, is of great importance. Filling this area permits reshaping of the oval outline of the face (jaw line). Any type of HA may be used but HAs with a long duration are more suitable.

With Voluma or Sub-Q products, it is easy to enhance the chin's profile (Fig. 8), which can avoid the placement of a surgical prosthesis.

Figure 8.

Chin remodeling.


Fillers are one of the major tools for rejuvenation of the skin. Bovine collagen was the first filler, which was used and safe to use (after double skin testing) for wrinkles and lip augmentation.2,7

In aesthetic dermatology, it is safer to use biodegradable agents rather than permanent. Complications of permanent agents are also permanent and much more difficult to treat than those observed of biodegradable agents.8

Since 1996, HA has been used as a filling agent. HA is a glycoaminoglycan polysaccharide present in the human body. Nowadays, HA is produced by bacterial fermentation (Streptococcus equinus principally); there is no risk of animal-derived contamination. As HA has no species specificity, there is no need for skin testing.

Experience with HAs is now substantial; we know that adverse events are rare, and, in most of cases, they will disappear with the product (biodegradability).1,9

The range of HAs available is wide, from slightly to highly viscous products. HAs give opportunity not only to fill wrinkles but also to increase volume; this is why it has progressively replaced collagen to become the “gold standard” among fillers.

With HA, we can do a broad rejuvenation of the face: thin HAs can be injected by mesotherapy to hydrate skin's surface, thicker HAs are useful to improve wrinkles, nasolabial folds, hollow under eyes, for lip augmentation and thickest HAs are used for increasing volumes.

Longevity depends on treated areas, stabilization and viscosity of injected HAs, and taking also into account the possibility of an individual response.

Longevity of natural human HA in the skin is very short (24–48 h); cross-linking increases this longevity. Degradation depends on thermal effect, enzyme (hyaluronidase), and free radicals interaction.

In vivo, from numerous recent studies, we learned the importance of HA in human physiology. HA is the main agent of the extracellular matrix, and apart from its hydrophilic structure, it has a lot of physiological functions. Specific cell receptors have been reported (CD44, RHAMM/CD168). By means of CD44 and HA interactions, mesenchymal stem cells are recruited to injured renal tissue and enhance renal regeneration.10 HA provides not only a physical scaffold to facilitate localization and retention of hemapoietic stem cells to the stem cell niche, but also directly affects the cellular functions of hemapoietic stem cells through specific receptors.11 HA induces vascular smooth muscle cell migration through CD168 receptors.12 HA through binding to CD44 and CD168 receptors acts on the formation of new blood vessels.13,14 HA inhibits osteoclasts differentiation and plays an important role into the regulation of bone metabolism.15

Anomalies of HA have been reported in fibromyalgia16 and sclerodermia,17 and it has been proven that, after ischemic stroke in humans, there is an increased production of low molecular HA and of hyaluronidase. In ankylosing spondylitis, it has been found that HA levels are increased and that they may be a biomarker of axial inflammation and disease severity.18

In vivo, endogenous HA fragments have wide-ranging and often opposing biological functions. Degradation of HA induces formation of polymers of decreasing sizes. Large fragments have a role of filler, are antiangiogenic, immunosuppressive, and impede cell differentiation. Smaller HA fragments are inflammatory, angiogenic, immunostimulatory, stimulate cell proliferation, and act as “danger signals.”19

In vitro, a recent study has demonstrated HA binding to CD44 receptor.20 This article demonstrated that HA significantly decreases expression of pro-inflammatory cytokine in rotator cuff disease.

In rabbit, it has been reported that after cartilage defects with microfracture, adjunction of HA gel resulted in regeneration of a new thicker and more hyaline-like cartilage.21 In mice dermatitis, HA has demonstrated some anti-inflammatory and antiallergic effects on skin lesions.22

Very few studies of in vivo physiologic actions of exogenous HA have been reported. Wang et al. did not find HA binding with specific CD44 receptors after injections for rejuvenation.23 They conclude that collagen production could be secondary to stretching by a mechanical effect.

We know that low-molecular HA is more prone than large-size HA to link to CD44 receptor in the skin and to stimulate fibroblasts. Following HA molecular size, some different physiologic actions may be encountered. With stabilized HAs, natural degradation process may create smaller fragments, which may have opposing biological actions.

In addition to a filling effect by its mechanical properties, exogenous HA may demonstrate several physiological functions, which interfere with healing process and rejuvenation.

Future research will give us a better understanding of all mechanisms of action.


For 10 years, we have used HA in aesthetic dermatology in Europe. This agent is safe, and we can choose from a wide range of HAs for enhancing the face.

We started first to fill wrinkles but progressively new procedures permitted us to restore facial volumes. However, we need to bear in mind that successful aesthetic treatments also require a minimum of artistic talent in order to achieve an overall natural look.

Better knowledge of physiologic HA functions will offer us in the near future the possibility to discover and to propose refinements in antiaging techniques.