Know your options: Dermal Fillers

Everything you need to know about choosing the right dermal filler for fine lines, wrinkles, elasticity or lip enhancement from Botox to Hyaluronic Acid (HA) the best, and worst. Make an informed decision with guidance.

The topic of dermal fillers is high on the agenda for Cosmetic manufacturers, wholesalers, retailers and buyers. Women are constantly looking for the most effective method of maintaining youth and beauty as they age – the most natural way possible. There have been rapid development in the field of dermal fillers since their introduction with the highly sought collagen fillers in the late 80s. Today, hyaluronic acid is one of the most popular ingredients in dermal fillers, biologically synthesised to mimic a naturally occurring compound there are little to no side-effects.

Dermal fillers

What You Should Know About Wrinkle Fillers

Injectable wrinkle fillers can give you a more youthful look for a fraction of what a traditional face lift costs. Most will fill lines and wrinkles in less than 30 minutes with results that can last from four months to more than a year.

Injectable wrinkle fillers, unlike Botox injections that relax the muscle under a wrinkle, fill the line or crease with one of several different substances. As a result, the line or crease seems to have nearly disappeared.

Wrinkle fillers can also be used as “volumizers,” plumping and lifting cheeks, filling out thin lips, and plumping sagging hands.

The treatment is fast and easy. But all wrinkle fillers have a downside, including the risk of allergic reaction and the formation of tiny bumps under the skin. In some cases, those bumps may be permanent. A bluish skin discoloration known as the Tyndall effect is also possible. The color change can last for several months, but there are treatments available. In very rare cases, skin cells may die if the wrinkle fillers are not used properly. Typically, the wrinkle fillers with longer-lasting effects are the ones more likely to cause side effects.

Not every wrinkle is right for every type of wrinkle filler. The least risks and best results come from using the right wrinkle filler correctly. That’s one reason why you should only have wrinkle fillers injected by a board-certified dermatologist or plastic surgeon.

To help you discuss your options with your doctor, here is a breakdown of the wrinkle fillers currently available. It includes their basic ingredients, how they work, their risks and benefits, and the best areas for treatment. Your doctor can help you choose the right one for you.

Hyaluronic Acid Wrinkle Fillers

The most popular category of wrinkle fillers is hyaluronic acid. Each type of hyaluronic acid wrinkle filler works in a slightly different way with varying results.

Side effects are rare, but they can include redness, swelling, and bruising at the injection site. The filler may also be seen beneath the skin as tiny bumps. This is a problem that often improves over time.

How long the results last varies from several months to over a year. Some research shows that repeated injections may help stimulate the body’s own natural production of collagen. That will help reduce the number of lines and wrinkles. There is also some evidence that less filler is needed over time to achieve the same look.

Hyaluronic wrinkle fillers include: (see more of this later) 

Wrinkle Filler: Juvederm Ultra/Juvederm Ultra Plus
Ingredient: Gel made of hyaluronic acid
Effects: Up to one year
FDA Approved for: Moderate to severe facial wrinkles and folds
FYI: Not recommended if you have severe allergies, particularly if you’re allergic to bacterial proteins

Wrinkle Filler: Restylane/Perlane
Ingredient: Hyaluronic acid particles suspended in a gel
Effects: Six months or longer
FDA Approved for: Moderate to severe wrinkles and folds.
FYI: Not recommended if you have severe allergies.

Collagen: Effects rarely last beyond 3-6 months, there is significant risk of allergic reaction, there are new approaches to the delivery method which are proving more successful with less chance of developing an allergic reaction;

Bovine Collagen: Injectable (ZyDerm, ZyPlast ) has been around the longest and is the least expensive. It is the most common form of collagen people develop an allergy to due to the steuctural difference between human collagen and bovine collagen. People suffering connective tissue diseases (rheumatoid arthritis, systematic lupus, scleroderma and dermatomyositis) are more likely to develop an allergic reaction. Bovine is used mainly for wrinkles of varying delth and depressed scars. Collagen is gradually degraded by the body’s enzymes so the effects tend to disappear after 3-6 months, with maintenance of the treatment required for long term results.

Human Collagen: (CosmoDerm, CosmoPlast, Autologen) similar to Bovine in terms of uses, durability and other properties. It has a lower risk of immune reactions and oesnt require allergy testing. Human collegen in more expensive, sources vary depending on the brand and include human tissue culture, cadaver tissue obtained at the time of death and partients own excess skin removed during cosmetic procedures.

Human acellular dermal matrix: This is a hman derms stripped of all cells and specially treated to increase stability and reduce the risk of immunological reactions. Acellular dermal matrix is typically obtained from the skin of human cadavers. Donor matrix serves not only as a filler but also to provide the scaffolding for the recipients’s own cells to attach to. The result is better tissues integration and durability. Still, as it is made up of collagen primarily, it is still gradually broken down by the body. This is used to repair deep lines, folds or furrows, it requires implantation via a small incision lasting 1-2 years. It can be injected but lasts only 6months via this method.

Fibroblast injections: Injected collagen is gradually broken up by the proteolytic enxymes and can only be replenished by more injections. An alternative approach is to inject collagen-producing cells (fibroblasts) instead of collagen itself. If injected fibroblasts take hold of the skin, they can keep producing collagen for a long time.. The downside to fibroblast method is that the tissue is faced with rejection problems. Companies like Isolagen (patented therapy) is harvesting the patients own fibroblast (from a small skin sample) and growing them in tissue culture, this is then injected into wrinkles and scars

Overview of Hyaluronic Acid based fillers: 

Long lasting, non toxic, fully biocompatible ( doesnt trigger immune responses).

Easy to remove, or adjust non invasively, easy to standadize and mnufacture. Affordable and available. HA is a nontoxic, biodegradable, biocompatable poymer naturally found in human skin. Com,pared to proteins, HA has a simple structure and is more stable, easy to produce.

A number of wrinkle fillers have been developed on the basis of HA. The most common HA based filler is the ‘stabalized non-animal hyaluronic acid gell) (NASHA)

NASHA brands:
Restylane (and variants)
Restylane (perlane – deep lines, facial contouring, lip engancement.
Restylane Touch  – very thin, superficial lines.
Restylane SubQ – replace fat loss in the face and create of restore a more defined facial contour
Juviderm –  smoother consistency than Restylane. Claim greater patient satifaction and reduced side-effects
NASHA has a number of advantages. The structure if very similar to human HA, very few people develop allergic or other immune reactions. HA is a synthesized by bioengineered bacteria, there is no reisk of contamination by animal or human pathogens. If the patient develops any bumps or irregularitits, HA can be broken down by hyaluronidase, which can naturally break down the HA and cause the filler to degrade quickly.

NASHA must be injected ever 6-12 months for maintained results.
Chronic allergic, inflammatory or other reactions may offur, Inflammation and swelling at injection site is common, usually resolving on its own in a few days.

OTHER HA sources:

There are a number of animal HA based fillers on the markets, Hylaform and Hylaform Plus contain HA extracted from rooster combs. The advantages and disadvantages are similar to NASHA, the main difference is that they come from animal sources and might present a somewhat higher risk of contaminnation with pathoens potentially harmful to humans.

$$ NASH (Restylane, Captique, Juvederm ) cost around 500-600 per cc (cubic centermeter) typical dosage per treatment is 3/4 – 2cc. Maintenance requires treatment every 6-12 months. Fillers based on animal origin can be 20-30% cheaper than NASHA.

Hydroxylapatite-based wrinkle fillers 

Chemically, hydroxylapatite is a calcium phosphate based mineral with characteristic hexagonal crystalline structure. The best known brand of cosmetic fillers based on hydroxylapatite is Radiesse, which consists of small hydroxylapatite microspheres (particles) suspended in a gel-like solution. The most common uses of hydroxylapatite-based cosmetic fillers are moderate-to-deep wrinkles, facial folds, loss of facial fat (lipoatrophy) and similar problems.

Some of the advantages of hydroxylapatite-based cosmetic fillers are similar to those of non-animal stabilised hyaluronic acid gel. Both are biocompatible and do not require allergy testing prior to use; both are not derived from human or animal tissue, which minimizes the risk of contamination with pathogens.

Hydroxylapatite-based cosmetic fillers are biodegradable (i.e. they slowly disintegrate after injection) but they last relatively long (about 12 – 18 month), which is more than collagen-based fillers (3-6 mo) or hyaluronic acid-based fillers (6 – 12 month). Therefore, fewer treatments are generally required to maintain results. If the injections of a hydroxylapatite filler have created any unacceptable irregularities, they tend to eventually dissipate on their own, even though it may take a relatively long time (longer than for most other biodegradable fillers).

Hydroxylapatite-based filles appear to stimulate the production of the body’s own collagen at the injection site, which may partly explain why a lesser volume of hydroxylapatite-based filler seem to equal or exceed the effects of a greater volume of other biodegradable fillers. In one study conducted in Germany and Spain, researchers compared hydroxylapatite-based filler Radiesse with a leading hyaluronic acid-based filler Restylane. It was reported that “although requiring approximately 33% less injection volume, the calcium hydroxyapatite product yielded significantly increased aesthetic improvement vs hyaluronic acid in 63% of patients at 6 months. Only 4% of patients achieved better results with hyaluronic acid; 33% achieved equal improvement with both agents.” More independent comparison studies are needed to put this result in perspective.

$$ Radiesse costs from $650 to $800 per syringe. It usually takes 1-2 syringes per treatment. The cost per unit volume is higher than for most other biodegradable filler. However, since Radiesse last longer and a smaller amount of it may be required for an equivalent effect, the total cost over time may actually be less that for alternative biodegradable fillers, such as Restylane or Juvederm.

While relatively long lasting, hydroxylapatite-based fillers do degrade and have to be re-injected every year or so to maintain results.

A short-lived inflammation and/or swelling at the injection site is relatively common. It usually resolves on its own in a day or two. Chronic allergic, inflammatory or other reactions seem to be very rare – at least as rare as with other common biocompatible filler/implant materials.

Occasionally, a hydroxylapatite-based filler injection may create a bump or an irregularity under the skin (as most other fillers might do). This is often a result of improper filler selection, incorrect dose or insufficient experience of the administering practitioner. In such a situation, hydroxylapatite-based filler is at a disadvantage compared to a hyaluronic acid-based filler. Correcting the result of hydroxylapatite injection will generally require a long wait or an invasive intervention. On the other hand, misapplication of hyaluronic acid-based filler can often be corrected by injecting hyaluronidase, an enzyme that breaks down hyaluronic acid

The idea to transplant the patient’s own tissue to correct cosmetic imperfections is not new. Indeed, the benefits of such approach would seem obvious. The implant should survive permanently, cause no allergy or rejection, and carry no intrinsic risk of disease transmission because, after all, it is your own “flesh and blood”. Other short and long-term risks are low as well. Sounds ideal. Unfortunately, the reality is somewhat messier. Typical cosmetic transplant-based fillers survive only partially after the injection and often require re-treatment. There results are often inconsistent and procedures are costly and more complicated than for most fillers. Still, successful transplant-based filler may provide good long-term results at low level of risk. The autologous (one’s own) transplant-based fillers currently on the market include autologous fat and cultured fibroblasts (key cells of skin dermis). Note that when we talk about transplant-based fillers we only refer to the ones containing live cells. The fillers lacking physiological activity cannot be categorized as a transplant, even if made of one’s own tissue

Cultured autologous fibroblast

One of the primary causes of wrinkles is the breakdown of the skin matrix components, most importantly collagen. A common way to quickly replenish lost collagen is to inject it. However, injected collagen is broken up by the proteolytic enzymes within about 2-4 months, after which the injection needs to be repeated. An alternative is to inject collagen-producing cells (fibroblasts) instead of collagen itself. If the injected fibroblasts take hold in your skin, they can keep producing collagen for a long time. However, the use of fibroblasts from donor skin is difficult because of tissue rejection problems. A better approach is to inject autologous (patient’s own) fibroblasts. The problem is that it would take a relatively large skin graft to obtain enough fibroblasts to inject. A far less invasive alternative is to take a small skin sample from a patient, extract the fibroblasts, grow them in tissue culture in sufficient quantities, and then inject into wrinkles and scars.

Such an alternative is indeed available under the brand name Isolagen. In theory, such approach should provide lasting results without the need to repeat the treatment. The results so far seem reasonably encouraging but this process is far more expensive than conventional collagen injections. Also, fibroblast injections for skin rejuvenation are still relatively new and more research is needed to better quantify the benefits.

Autologous Fat

Autologous fat transfer (a.k.a. structural fat grafting, fat injections, etc.) is a procedure whereby a patient’s own fat is harvested (e.g. from the abdomen), processed and injected into the subcutaneous tissue to add extra volume to depressed areas. In particular, far grafting is often used to restore lost facial volume in the eye area, cheeks, lips, under deep smile lines and so forth. Since the procedure involves autologous (patient’s own) fat, there is no risk of rejection or disease transmission. Generally, some of the injected fat integrates in the treated area and stays permanently (for at least a year and often much longer) while the rest dissipates over a few months. Until late 90s, autologous fat transfer had been the only widely-used transplant-based procedure to fill cosmetic facial defects.

The procedure, which is usually done on an outpatient basis within one day, is more complicated than typical fuller injection but still relatively straightforward. The fat is harvested under local anesthesia using suction and a special aspiration needle. Then it is purified, homogenized and treated to prepare for injection. Finally, the fat is injected under local anesthesia in the subcutaneous tissue in the desired area. However, due to many subtleties of the technique, the surgeon’s skill and experience are important. The biggest issue is that only a percentage of the injected fat takes hold in the treated area. Furthermore, this percentage may vary widely: from about 10% to 50% depending on a variety of factors. Many surgeons have their favorite harvesting and injection techniques and claim higher than average clinical longevity of the grafts. However, the factors specific to the individual patient and area treated play at least as big a role. If you are interested in fat injections you do need to find an experienced dermatological surgeon but be aware that the longevity of the graft is hard to predict and may be below your expectation. You may have to undergo multiple treatments until sufficient fat has integrated long-term in the treated area – with commensurate inconvenience and expense

Synthetic polymer-based wrinkle fillers 

In a perfect world, a wrinkle fillers should be completely biocompatible, i.e. they should be as biochemically close to the patient’s own tissue as possible. Some of the fillers on the market, such as human collagen or hyaluronic acid gel, are virtually identical to biopolymers found in normal human skin. The problem is that if you inject polymers derived from or biochemically similar to natural skin matrix, they will “age” just as skin matrix does. In particular, they will be degraded by the skin’s own enzymes and/or react with damaging metabolites or free radicals. As a result, the effects of such “natural” fillers as collagen or hyaluronic acid gel usually lasts just a few month, after which a costly re-treatment is required to maintain results.

The more permanent alternative is to use synthetic polymers that are either non-biodegradable or degrade slowly. However, developing a synthetic polymer suitable as a dermal filler presents a number of challenges: it should have a very low risk of allergic and immune reactions; it should not migrate outside the treated area; it should not be toxic and should be mechanically similar to natural skin matrix. There has been some degree of success on that path, although the perfect long-lived filler remains elusive. Below we discuss some of the more successful types of permanent fillers in use today.

Poly-L-lactic acid

One approach to developing nontoxic synthetic polymers is to use natural nontoxic monomers. (Monomers are repeating chemical units comprising a polymer.) Should such a polymer degrade into monomers inside the tissue, no or little toxicity would result because its monomers are nontoxic substances found naturally in the body. One reasonably successful implementation of such approach is poly-L-lactic acid (sold under the brand of Sculptra), a slow-biodegradable polymer made up of L-lactic acid. L-lactic acid is a nontoxic, natural by-product of anaerobic metabolism of glucose. If you ever had sore muscles after excessive workout, you have survived a lactic acid overload. The amount of L-lactic acid released by poly-L-lactic acid filler is far less than that and is considered quite safe. While poly-L-lactic acid does gradually degrade inside the human body, it does so much slower that more common biodegradable fillers, such as collagen or hyaluronic acid. The average durability of Sculptra is 2 years, as opposed to 3-6 month for collagen. Sculptra is used mainly for deep wrinkles or to fill out facial contours (e.g. cheeks, jaw line) affected by loss of fat due to disease or natural aging. Sculptra has been developed as a less invasive and more consistent (in terms of results and durability) alternative to fat grafting.

Sculptra is generally well tolerated and requires no allergy test. The most common side effects of Sculptra include tenderness, redness, bruising, or swelling upon injection. These side effects are usually temporary, and if present tend to decrease over the next 3 to 15 days. Other side effects may include small bumps under the skin in the treated area which may appear over time. These bumps are not always visible, and often are only detected by pressing on the skin. Notably, the results of Sculptra injections are not obvious immediately after treatment and tend to fully develop over the next 6-8 weeks. The reason is that the filling effect of poly-L-lactic acid is more due to the reactive synthesis of new collagen rather than the injected polymer itself

Polyacrylamide and Polyalkylimide gel

Polyacrylamide (Aquamid) and polyalkylimide (Bio-Alcamid) are synthetic polymers that can hold large amounts of water, forming a gel with mechanical properties resembling some human tissues. Such gel is injectable and non-biodegradable. The results are permanent, although the manufacturers claim the fillers can be removed by aspiration in case of overtreatment or other problems. These gels are typically used to treat relatively large defects, such as deep lines, folds and furrow, pitted scars and fat loss due to aging or disease. They are not used for fine lines or small wrinkles. Even though the monomers that make up polyacrylamide or polyalkylimide are toxic, the polymers themselves are chemically inert. The manufacturers and many experts believe that they degrade in the body so slowly that the risk of toxicity is very low. So far, there seems to be no evidence to the contrary. Both of these polymers, but especially polyalkylimide are believed to integrate into the skin matrix (they get encapsulated by the body’s own collagen) and, as a result, rarely migrate away from the treatment site. Polyacrylamide and polyalkylimide may be something to consider for those who wish permanent results and have relatively large defects to correct but would like a “back-out” option. As mentioned, these polymers can be removed or adjusted via aspiration. However, it is unclear whether a complete removal can be easily accomplished


Polymethylmethacrylate (PMMA) is a synthetic polymer with a long history of use in medical implants. It has been used in bone cement, dentures, pacemaker covers and so forth. It is considered nonbiodegradable, relatively nontoxic and chemically inert. As a dermal filler, it is being used under the brand of ArteFill (a.k.a. ArteColl), which, in essense, is PMMA microspheres (microscopic particles of spherical shape about 30-40 microns in diameter) suspended in bovine collagen solution. The role of collagen solution is to provide a smoother suspension and possibly aid in skin matrix integration. After the injection of ArteFill, the bovine collagen is degraded over about 2-3 month. At the same time, PMMA gets encased in the patient’s own collagen produced in response to foreign material and bovine collagen. This results in good integration of the filler and produces highly durable results with low risk of filler migration. There have been reports of cases when the injections area became hardened or bumpy, possibly due to excessive formation of the scar tissue. Whether this was primarily to the reaction of PMMA or bovine collagen remains unclear. ArteFill requires prior allergy test due to bovine collagen component

Other synthetic polymeric wrinkle fillers

Many other fillers based on synthetic polymers have recently come or are about to come to the market. Covering every possible brand is beyond the scope of this article. However, it is worth keeping in mind that most of these synthetic newcomers have little or no long-term data, even when approved by the FDA. Before opting for a cutting-edge, newly branded filler, it is prudent to look at better established ones first.


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