Wrinkle injections with filler materials are considered to be one of the most proven and safest methods of smoothing existing wrinkles and rejuvenating the face. A proven filler is hyaluronic acid, a natural molecule that exists in the body between the cells as a filling material. In small quantities, injected under existing facial wrinkles, existing wrinkles can be padded and smoothed. Filler applications are particularly effective in the area between the nose and the corners of the mouth, on the lips and eyelids.

Filler (Hyaluron)

The injection of wrinkles with tissue fillers (synonym: "filler") serves to improve the external appearance without surgery. Fillers can be injected without downtime to correct wrinkles and increase volume.

Today's injection techniques are based on decades of research and experience. Volume build-up with the transplantation of autologous fat tissue from the upper arm into the face was described in the 19th century (Neuber, F. 1893. Kongressband/Deutsche Gesellschaft für Chirurgie). Injection with a filler product to build up facial contours was undertaken at the beginning of the 20th century (Gersuny, J. S. 1903. Zentralblatt für Chirurgie).

Only with the production of safe and effective fillers did tissue injection become one of the most common forms of treatment in plastic surgery. Hyaluronic acid as a tissue filler (Zyderm I) was first approved by the American health authority FDA in 1981 (Ozgentaş H.E., et al, 1994, Ann Plast Surg). The number of filler treatments has more than doubled worldwide from 2010 to 2018. In 2018, an estimated 3.8 million treatments were performed worldwide (ISAPS Global Statistics).

How long does a hyaluron injection last?

The breakdown of the injected hyaluronic acid depends on the following parameters:

  • the concentration of hyaluronic acid,
  • the size of the hyaluronic acid molecules,
  • the treated body region,
  • the amount of hyaluronic acid injected,
  • the metabolism of the respective person and
  • the degree and type of cross-linking of hyaluronic acid.

The effect of hyaluronic acid treatments only lasts for a limited time, depending on the hyaluronic acid preparation used. This can range from three to twenty-four months for the hyaluronic acid preparations commonly used on the face (Fallacara A. et al, 2017, Facial Plast Surg). The result of a hyaluronic acid injection of the cheeks or tear ducts is more long-lasting than the treatment of the wrinkle between nose and mouth (nasolabial fold) (Park KY et al., 2017, Dermatol Surg).

Lipofilling with own fat

Lipofilling is an interesting alternative to the use of hyaluronic acid. On the one hand, the use of the body's own material is a less risky method - there is no danger of nodulation, rejection or allergic reactions. On the other hand, the fat can be removed from places where it is annoying anyway.
Clear advantages result from the fact that the living fat tissue contains different cell types - for example stem cells, which have a regenerative effect and can thus improve the appearance of the skin beyond pure filling. Since the cells grow in large numbers at the transplant site, the beautifying effect of lipofilling usually lasts much longer; post-injection as with hyaluron is usually not necessary.

Is the wrinkle injection painful?

With every treatment, whether surgical or non-invasive, we take care of your relaxation and well-being in a variety of ways. The following measures contribute to your painless hyaluron injections:

  • An anesthetic cream is applied before the treatment so that the needle puncture does not cause pain.
  • If there is no allergy, mixing the hyaluronic acid with a local anesthetic prevents the development of pain.
  • Some background music distracts from the pain and promotes relaxation.
  • To reduce the sensation of pain, we use vibration anesthesia. With a small handpiece (NüeVibe™) vibrations are transmitted to the treated skin region. A vibrating metal rod interrupts the transmission of the pain sensation.
  • The finest cannulas are used for the injection of wrinkles and lip injections. The puncture of these special cannulas is particularly gentle and is usually hardly noticed.

What types of tissue fillers are there?

There are basically 4 categories of tissue fillers:

  • Calcium Hydroxyapatite Tissue fillers (e.g. Radiesse®) are broken down by the natural metabolism after about 12 to 18 months. They are characterized by a high viscosity.
  • Poly-L-lactic acid tissue fillers (e.g. Sculptra®) stimulate the production of new collagen, which leads to more volume. It therefore takes about 6 months until the final result becomes visible.  
  • PMMA (polymethyl methacrylate) and bovine collagen tissue fillers (e.g. Bellafill®) are not degradable by the body.
  • Hyaluronic acid tissue fillers (e.g. Juvéderm® Volbella, Volift, Voluma; Restylane® Volyme, Defyne, Kysse, Skinboosters) consist of naturally occurring glycosaminoglycans.

The various products are characterized by manufacturing processes, cross-linking and size of molecules, concentration and viscosity. As a rule, the results of hyaluronic acid preparations last between six months and two years. A major advantage of hyaluronic acid tissue fillers is that they can be rapidly degraded with the enzyme hyaluronidase (Hylase©).

Are fillers medical devices or pharmaceutical products?

Fillers are classified as medical products, such as dressing materials or visual aids. Hyaluronic acid preparations for injections are not subject to the strict drug law. The CE marking for medical products provides for a compatibility check. The approval as a medicinal product is much stricter. It includes, for example, proof of efficacy and safety in meaningful clinical studies. These studies require considerable financial resources as well as extensive human and material resources. Recognised and established companies find it easier to raise these funds.


Who gets to inject Filler?

In principle, licensed doctors and alternative practitioners are allowed to inject hyaluronic acid. For a good result not only the quality of the hyaluronic acid is important, but also the skills and knowledge of the user. The following information should help you to decide who to trust:

  • As before any medical treatment, a consultation and examination is first necessary to establish the exact findings. Making a diagnosis in the field of plastic and aesthetic surgery requires appropriate training and professional experience.
  • Often the combination of different procedures leads to the best possible result (for example microneedling, PRP, Botox). In some cases, completely different treatment techniques are required (for example, autologous fat injection, tightening operations, silicone implants). Knowledge and experience of these techniques are important in order to be able to advise you correctly.
  • Scientific training and constant updating of knowledge are necessary for a careful consideration of different medical treatment methods.
  • A foresighted treatment plan is a basic requirement for a good result. This requires an assessment of the individual health risks and knowledge of preventive measures.
  • An aesthetic treatment is a medical treatment. Before any medical treatment, it is necessary to be informed about possible risks. An education by non-medical personnel is in violation of the German Civil Code, paragraphs 630c paragraph 2 p. 1, 630e paragraph 1, paragraph 2 p. 1 no. 1.
  • The practitioner should be able to control possible complications. Emergency medication such as Hylase® and a medical emergency kit should be available. The type of application and dosage of the emergency medication should be familiar.
  • The treatment requires a precise knowledge of the anatomy, the interaction of the cells, the processes in the tissue and the metabolism. Experience in the implementation and treatment of complications is necessary.
  • Heilpraktiker may call himself any person who has a secondary school leaving certificate and passes an examination at the responsible health office. Training is voluntary. The specialist for plastic and aesthetic surgery has undergone an admission procedure to study medicine. The medical studies comprise 5,500 hours of theoretical and practical instruction and three state examinations. A specialist in plastic and aesthetic surgery has completed practical training of approximately 11,600 hours and passed an oral examination. The European specialist title requires the passing of an additional oral and written examination.

Qualification and experience matter

The popularity of treatment with wrinkle filling materials must not obscure the fact that professional know-how is necessary to achieve optimum results and minimise risks. A secondary school leaving certificate and an examination at the health authority are sufficient for the granting of permission to practice as a non-medical practitioner. The training as a Heilpraktiker is voluntary. Surgery is a craft. However, it does not only require training to be able to practice the profession of a surgeon. Much knowledge and experience is necessary to be able to recognize when a treatment measure is appropriate and when not. Mastering complications and treatment alternatives also requires comprehensive training. The terms "cosmetic surgeon", "aesthetic surgeon" or "cosmetic surgeon" are not protected. The situation is different with the professional title "Plastic and Aesthetic Surgeon", these physicians have all completed a corresponding six-year training course.

What is hyaluronic acid?

When examining the vitreous body of the eye in 1880, a special transparent substance was described and called hyalomucin ("hyalos" ancient Greek for glass) (Beauregard, 1880, J de l'Anat et de la Physiol Norm et Pathol de l'Homme et des Animaux). Later, a building block of this substance was discovered: uronic acid or glucuronic acid (Meyer K., et al. 1934, J Biol Chem). From this the name hyaluronic acid is derived. Hyaluronic acid dissolved in water is called sodium hyaluronate. Hyaluronan is the scientific umbrella term for the dry substance hyaluronic acid and the sodium hyaluronate dissolved in water.

Hyaluronic acid is a natural building material of the human body, which occurs in identical form in all vertebrates. Hyaluronic acid consists of a chain of a sugar compound that is repeated 10,000 to 25,000 times (glucuronic acid and acetylglucosamine). Hyaluronic acid is important for the health and function of all organs. Collagen and hyaluronic acid are essential components of a scaffold that connects the cells in the body tissue. Hyaluronic acid is used in medicine as a "lubricant" and "shock absorber" for worn joints (arthrosis), among other things.

Hyaluronic acid binds more water than almost any other substance in nature. The reasons for this are the water-attracting sugar components and the long chain of sugar compounds of hyaluronic acid. It stores moisture and increases the skin's resistance. One gram of hyaluronic acid binds about 500 milliliters of water (Ogston AG, et al. 1966, Fed Proc).

Its ability to store water is interesting for aesthetic medicine. It is also pressure stable. Both these properties make hyaluronan ideal for padding slack skin areas and underfilling wrinkles. Irregularities of the skin and sunken skin areas can be balanced with hyaluron. Hyaluron is also used to define facial or body contours more clearly and to make lips fuller.

Where does hyaluronic acid occur?

Hyaluronic acid is widely distributed in nature: It occurs in humans, vertebrates, molluscs, bacteria, algae and certain yeast fungi (De Oliveira J.D., et al., 2016, Microb Cell Fact). In humans, hyaluronic acid is present in the joints, skin, intervertebral discs, lungs, eyes and brain. In the deepest layer of the skin (stratum basale) there is a high concentration of hyaluronic acid. Interestingly, the highest concentration of hyaluronic acid is found in the umbilical cord (4 milligrams per milliliter).

The body of a 70 kilogram person contains about 15 grams of hyaluronic acid (Stern R. 2004. Eur J Cell Biol). The largest amount of hyaluronic acid (7-8 g in adults) is found in the skin (Reed RK, et al. 1988. Acta Physiol Scand).

Hyaluronic acid fills the space between the cells (extracellular matrix). This space can be imagined as a scaffold consisting of hyaluronic acid, collagen and sugar molecules. Enzymes on the surface of specific cells, also called fibroblasts, produce hyaluronic acid. The enzymes assemble the chain of hyaluronic acid inside the cell. The longer chain of hyaluronic acid is released into the intercellular space (extracellular matrix).

What does hyaluronic acid do in the body?

Many studies are intensively concerned with the role of hyaluronic acid. Hyaluronic acid influences many processes in our body. Hyaluronic acid controls among other things:

  • the cohesion of cells,
  • the migration of cells,
  • the multiplication of cells,
  • the healing of wounds and
  • serves as a lubricant in the joint fluid,
  • the shape of the vitreous body of the eye,
  • the conduction of impulses from nerves and
  • the development and maturation of the child in the womb.

Many processes are controlled by the hyaluronic acid triggering a reaction like a key in a lock on a cell surface. One of the most common "locks" for hyaluronic acid is called CD44. This lock is present on almost all cells of the human body.

The control mechanisms are highly complex and are influenced by many parameters. In fact, in the body one key can open different locks and different keys can open one and the same lock. A variety of different signaling molecules (growth factors, cytokines and extracellular matrix proteins such as fibronectin) can open the CD44 lock. The effect of hyaluronic acid also depends on the length of the hyaluronic acid chain and the concentration of hyaluronic acid (Cyphert J.M., et al., 2015, Int J Cell Biol).

How is hyaluronic acid injected?

A hyaluronic acid injection rarely takes longer than 20 minutes. The preparations are for your comfort and safety. Hygienic work and surgical disinfection are a matter of course for us. Before the injection, make-up is removed and the skin is carefully disinfected.

Depending on the region treated, a different technique of injection is used (linear technique, fan technique, criss-cross technique, vertical technique). Special atraumatic cannulas reduce the risk of bruising. The hyaluronic acid is injected gently and specifically into the corresponding tissue layer.

For the treatment of drooping cheeks or the build-up of cheekbones, the filler is inserted into deeper layers. A superficial treatment serves to correct fine skin wrinkles and improves skin moisture and elasticity.

Cooling pads are then applied to prevent swelling and bruising. You can resume your normal daily routine a few minutes after the treatment. Since hyaluronic acid binds a lot of water, the result can still change slightly until the second week.

How is hyaluronic acid broken down?

Approximately one third of the total amount of hyaluronic acid in the human body is broken down and newly formed every day (Volpi N, et al. 2009, Curr Med Chem). Under normal circumstances, hyaluronic acid is broken down after only a few hours. With age, less and less hyaluronic acid is produced. Between the ages of 19 and 47, the skin consists of 0.03 percent by weight of hyaluronic acid. At the age of 60 or 75 years the percentage decreases to 0.015 or 0.007 percent respectively. Furthermore, the chains of hyaluronic acid become shorter with age (Longas MO, et al. 1987 Carbohydr Res). The consequences are dry skin and wrinkles.

Hyaluronic acid is broken down in the human body by enzymes (hyaluronidases) and by chemical reaction with oxygen. The broken down building blocks of hyaluronic acid are broken down in the liver to water and carbon dioxide. Hyaluronic acid is broken down at different points in the body at different rates. For comparison, the time span is given after which half of the hyaluronic acid is broken down (half-life). The half-life of hyaluronic acid in the skin is 24 hours, in cartilage 1-3 weeks and in the vitreous body 70 days (Schiraldi C., et al, 2010, Biopolymers).

How do hyaluron products differ?

The injection of hyaluronic acid was approved in Europe in 1996 and for the first time in the USA in 2003 for the treatment of facial wrinkles. Hyaluronic acid preparations for wrinkle treatment differ, for example, in the following properties:

  • the concentration of hyaluronic acid (milligram per milliliter),
  • the size of the hyaluronic acid molecules,
  • the proportions of high and low molecular weight hyaluronic acid,
  • the degree and type of cross-linking of hyaluronic acid,
  • the ability to bind water (millilitres per gram),
  • the tendency to return to the original shape (modulus of elasticity: G' in Pascal, the higher the value the firmer the gel),
  • the viscosity of the gel (viscosity module: G'' in Pascal, the lower the value, the thinner the gel or more simply the injection with wafer-thin needles and low pressure),
  • Quotient of viscosity and elasticity (Tan Delta value: the lower the value, the firmer the gel),
  • the cohesion of the gel (cohesiveness),
  • the addition of a local anaesthetic.

A dense cross-linking of the molecules, a high concentration and a high molecular weight of hyaluronic acid slow down the body's normal breakdown. The viscosity of the gel increases with increasing molecule size and concentration. The addition of a local anaesthetic (for example lidocaine) reduces the elasticity and viscosity of a gel. Elasticity and viscosity are measured with a rheometer.

How is hyaluronic acid produced?

Hyaluronic acid is used in medical and medicinal treatments, as a cosmetic product and as a food supplement. Accordingly, the biotechnological production is being researched intensively. The goal of these efforts is the production of pure hyaluronic acid, resource-saving and cost-effective. Therefore, certain bacterial strains are used in the modern production of hyaluronic acid (Tezel A, et al., 2008, J Cosmet Laser Ther). This process is also called NASHA (non-animal stabilized hyaluronic acid). The extraction of hyaluronic acid from animal tissue is time-consuming and labor-intensive and is therefore rarely used. Animal hyaluronic acid has ten to fifteen thousand sugar compounds per chain. Bacterial hyaluronic acid, in contrast, has four to six thousand sugar compounds per chain. The hyaluronic acid produced by bacteria is classified as harmless by the American health authority (FDA: Food and Drug Administration) (Widner et al. 2005).

The degree of cross-linking indicates the percentage of sugar compounds of hyaluronic acid that are linked to another chain of hyaluronic acid. A degree of crosslinking of four percent means that four out of every hundred sugar compounds in a chain are crosslinked. A higher degree of cross-linking is associated with a higher viscosity and a lower ability to bind water. Linked chains of hyaluronic acid are broken down more slowly by enzymes. The effect of hyaluronic acid injections lasts longer.

The most commonly used substance for cross-linking hyaluronic acid is 1,4-butanediol diglycidylether (BDDE). BDDE has been used since 1986 (Weiss C. et al., 1986, Bull Hosp Jt Dis Orthop Inst). The stable compound of BDDE extends the hyaluronic acid effect up to one year. Through a complex purification process, the unbound BDDE is removed up to the detection limit. Traces of BDDE occur in concentrations of 1 to 2.46 micrograms per liter (ppb: parts per billion) (Figaldo F., et al., 2018, Med Devices Auckl). The BDDE is degraded in the liver by a specific enzyme (Cytochrome P450) into glycerol and butanediol. Both substances will in turn be broken down into carbon dioxide. Other substances such as divinyl sulfone are hardly used anymore, as BDDE is more compatible than divinyl sulfone (De Boulle K, et al., 2013, Dermatol Surg).

Which hyaluronic acid is the best?

A high quality product should have the following characteristics:

  • There should be no doubt about the safety of the filler.
  • The product should be well tolerated by the tissue.
  • It should not cause allergies.
  • The filler should be easy to use.
  • The substance should be durable.
  • The result of the injection should look natural.
  • The tissue filler should not spread throughout the body.
  • The filler should be dissolvable if necessary.
  • The product should not be too expensive.

The selection of the optimal tissue filler depends on the individual needs. A filler for treating lips has different properties than a filler for improving sagging cheeks.

Approval by the US Food and Drug Administration (FDA) is subject to more stringent requirements. The data from good scientific studies, experience over many years and the approval of the US Food and Drug Administration (FDA) are quality features of a filler product. Published scientific studies exist almost exclusively on FDA approved products. Nevertheless, there are hardly any independently financed studies of treatment results. Fact-based objective differences in treatment results with Belotero® Balance, Juvéderm® Voluma and Restylane® could not be proven (Santer V., et al., 2019, Dermatol Surg).

Hyaluronic acid as a food supplement

Hyaluronic acid as a food supplement is absorbed by the body to about ten percent and stored in various organs (Balogh L., et al., 2008, J. Agric. Food Chem. 2008). Several comparative studies show that the intake of 40 to 240 milligrams of hyaluronic acid over four to twelve weeks leads to an improvement of skin hydration (Kawada C., et al., 2014, Nutr. J.). There is also evidence that supplementation with hyaluronic acid relieves knee pain (Oe, M., et al, 2016, Nutr. J.). The number of persons examined and the duration of the examination are not always very meaningful. The independence of the investigators is also questionable in certain studies (Göllner I., et al, 2017, J. Evid. Based Complement. Ageing. Med.). For the improvement of the skin appearance the combination of food supplement, skin care cream and a hyaluronic acid injection seems promising (Kawada C., et al, 2015, J. Photochem. Photobiol. B.).


What should be considered before an injection?

Hyaluron injections are a safe treatment with few side effects. The risks are even lower if you take certain precautions.

Blood-thinning medications such as aspirin or diclofenac affect blood clotting. If you can do without these medications, you will prevent the development of bruising. Certain vitamins (vitamins E and A) and food supplements (ginkgo biloba, green tea, garlic capsules, omega-3 fatty acids, echinacea, St. John's wort) also inhibit blood clotting. As a rule, it is sufficient to stop these blood-thinning substances ten days before the injection.

Postpone the treatment if you are currently suffering from cold sores. If the cold sore has healed completely, but you are particularly susceptible, preventive treatment may be considered.

Thorough but gentle skin cleansing on the day of treatment reduces the number of germs on the skin. Remember that immediately before the treatment make-up must be removed for hygienic reasons.

What should be considered after a filler treatment?

Gentle cooling after a filler treatment prevents the development of reddened skin. The treated areas should not be massaged. Alcohol consumption, especially red wine, causes dilation of the vessels, which in turn promotes the development of bruising. It is therefore advisable to avoid excessive alcohol consumption after a treatment.

There is no published evidence that the use of make-up after treatment increases the likelihood of inflammation. Nevertheless, we advise caution, as even the smallest puncture in the skin can allow germs to enter the body and cause inflammation.

Author's statement

Author: Stéphane Stahl, MD, PhD. There are no financial relationships with the pharmaceutical or medical device industries that could have influenced the above text. Any reproduction, even partial, is permitted for personal use only. All texts used on this website are protected by copyright.

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