Fillers: complete guide to injectable fillers

Fillers: complete guide to injectable fillers

Fillers—also called dermal fillers or injectable fillers—are substances that a doctor injects under the skin to restore lost volume, define facial contours or improve skin quality. Although the term "filler" translates literally as "filler," today it encompasses a much broader family of injectables that includes collagen biostimulators and skin biomodelers. This guide covers the complete landscape: from hyaluronic acid fillers to polynucleotides and autologous fat, through calcium hydroxyapatite, polylactic acid and hybrid products of the latest generation. The goal is for you to understand what each material does, how long it lasts, whether it is reversible and which areas it works best for.

In summary

• Fillers are divided into three functional categories: fillers (immediate volume), biostimulators (gradual collagen production) and biomodelers (skin hydration and quality).
• Hyaluronic acid (HA) is the most used material and the only one reversible with hyaluronidase; calcium hydroxyapatite, polylactic acid and polycaprolactone are not reversible.
• Duration ranges from 6 months (skinboosters, biomodelers) to more than 2 years (polycaprolactone, polylactic acid), depending on the material and treatment area.
• Regulatory agencies—FDA, EMA, COFEPRIS, ANVISA, INVIMA—classify dermal fillers as medical devices, not drugs.
• Safety depends on both the product and the injector: specialized medical training and knowledge of vascular anatomy are as important as material quality.

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What are fillers or injectable fillers?

Fillers are biocompatible substances that are injected into different layers of facial or body tissue to correct wrinkles, restore volume or improve skin texture. The FDA classifies them as Class III medical devices—the category of greatest regulatory control for devices—which means each product must demonstrate safety and efficacy through controlled clinical studies before receiving approval. It is important to distinguish fillers from botulinum toxin (Botox, Dysport). Botulinum toxin is a neuromodulator: it temporarily relaxes the muscles that cause expression wrinkles. Fillers, on the other hand, act on dermal or subdermic tissue, providing volume, stimulating collagen or hydrating from within. They are complementary tools, not interchangeable. The universe of aesthetic injectables has grown enormously over the last decade. It is no longer just about "filling" wrinkles: today there are products specifically designed to stimulate natural collagen production, remodel skin quality or combine both functions in a single injection.

Taxonomy: fillers, biostimulators and biomodelers

There are three functional categories of aesthetic injectables, and understanding them is key to choosing the right treatment. These categories are not mutually exclusive: some products, such as calcium hydroxyapatite, can belong to more than one depending on how they are used.

Fillers (volumizing fillers)

Fillers provide immediate volume to the tissue where they are injected. The result is visible from the same session. They include cross-linked hyaluronic acid fillers (Juvéderm, Restylane, Belotero, Teoxane RHA), calcium hydroxyapatite in standard concentration (Radiesse) and autologous fat. Their main function is to restore volume in cheekbones, lips, chin, jawline or nasolabial folds.

Biostimulators

Biostimulators do not provide volume immediately (or do so in a limited way). Their main mechanism is to activate fibroblasts to produce new collagen gradually over weeks or months. Results are progressive and longer-lasting than conventional fillers. This category includes polylactic acid (Sculptra), diluted or hyper-diluted calcium hydroxyapatite (diluted Radiesse), polycaprolactone (Ellansé) and hybrids like HarmonyCa (which combines immediate filler effect with biostimulation).

Biomodelers

Biomodelers improve overall skin quality—hydration, elasticity, luminosity—without adding volume or changing facial contours. They act at the dermal level, stimulating collagen and elastin production diffusely. They include non-cross-linked hyaluronic acid in high concentration (Profhilo), skinboosters (Restylane Skinbooster, Juvéderm Skinvive), polynucleotides/PDRN (Rejuran, Remedium) and polyrevitalization solutions (NCTF).

Types of fillers by material

Hyaluronic acid (HA)

Hyaluronic acid is the most widely used material in dermal fillers worldwide. It is a natural polysaccharide present in the skin, joints and connective tissue, with an extraordinary capacity to retain water—up to 1,000 times its weight. In injectable fillers, HA is cross-linked (chemically cross-linked) to form a stable gel that resists enzymatic degradation and provides volume for months. Formulations vary in degree of cross-linking, concentration, cohesivity and elasticity, which allows designing products specific to each area: firm gels for cheekbone or chin projection, soft gels for lips or periorbital area. The most established brands include Juvéderm (Allergan/AbbVie), Restylane (Galderma), Teoxane RHA and Belotero (Merz). Main advantage: it is the only material reversible with hyaluronidase, an enzyme that dissolves it in a matter of hours. This makes it the option with the greatest safety margin. Duration: between 6 and 18 months depending on the product and area of application. For a detailed comparison between hyaluronic acid brands, consult our guide to hyaluronic acid brands.

Calcium hydroxyapatite (CaHA)

Calcium hydroxyapatite is a biocompatible mineral naturally present in bones and teeth. Radiesse (Merz) is the reference product: it consists of CaHA microspheres suspended in an aqueous carboxymethylcellulose gel. In its standard concentration, Radiesse functions as a volumizing filler with immediate effect. Once injected, the carrier gel provides initial volume; over time, CaHA microspheres stimulate neocollagenesis (production of type I and III collagen) before being reabsorbed by the body. In its diluted or hyper-diluted form—mixed with saline and lidocaine—Radiesse transforms into a pure biostimulator: it distributes over broader areas to improve skin quality, firmness and elasticity without providing localized volume. This dual-function versatility (filler or biostimulator depending on dilution) is unique to CaHA. Reversibility: it is not reversible with hyaluronidase or any other injectable enzymatic agent. The material is reabsorbed naturally over time. Duration: 12 to 18 months as a volumizing filler; the biostimulation effects on skin quality can extend several more months.

Polylactic acid (PLLA)

Poly-L-lactic acid is a synthetic biodegradable polymer used for decades in absorbable sutures and other medical devices. Sculptra (Galderma) is the reference aesthetic product based on PLLA. Sculptra does not provide significant immediate volume. PLLA microparticles cause a controlled inflammatory response that activates fibroblasts, generating new collagen production gradually over weeks and months. Results begin to be visible between the second and third month, and reach their maximum effect between 4 and 6 months after the last session. The usual protocol requires 2 to 3 sessions separated by 4 to 6 weeks. The cumulative effect of the sessions is what produces the gradual and natural volumetric restoration. Reversibility: it is not reversible. PLLA biodegrades naturally. Duration: up to 24-25 months after completing the protocol.

Polycaprolactone (PCL)

Polycaprolactone is a biodegradable polyester that, like PLLA, stimulates the production of type I collagen. Ellansé (Aqtis Medical/Sinclair) is the main product in this category. Ellansé offers a dual effect: immediate volume thanks to the carboxymethylcellulose carrier gel, plus gradual biostimulation as PCL microspheres induce neocollagenesis. Unlike PLLA, it usually requires only one session. Objective studies with 3D volumetric analysis have documented an increase in volume of 50-150% above baseline at two years, indicating significant levels of new collagen formation. Ellansé is available in variants with different durations: Ellansé S (up to 18 months) and Ellansé M (up to 24 months), differentiated by the initial length of the PCL polymer chain. Reversibility: it is not reversible. Duration: 18 months to more than 2 years depending on the variant. Availability: approved with CE marking in Europe and available in Latin America and Asia, but does not have FDA approval in the United States.

Hybrid fillers: CaHA + HA

HarmonyCa (Allergan Aesthetics/AbbVie) is the first hybrid injectable that combines calcium hydroxyapatite microspheres suspended in a hyaluronic acid gel in a single syringe, without the need for reconstitution. This design offers a dual mechanism: HA provides an immediate filling and support effect, while CaHA microspheres induce neocollagenesis in the medium and long term. The result is an immediate lifting effect that improves progressively as new collagen integrates into the tissue. Reversibility: partial. The HA component may respond to hyaluronidase, but the CaHA component is not reversible. Duration: up to 2 years.

HA biomodelers: Profhilo and skinboosters

Profhilo (IBSA) is ultrapure hyaluronic acid with high concentration (64 mg in 2 ml) produced using NAHYCO technology, which thermally stabilizes cooperative hybrid complexes of high and low molecular weight HA without chemical cross-linking agents. It is not a conventional filler or revitalizer: it is defined as a biomodeler. Injected at 5 points per hemiface (BAP technique), Profhilo diffuses through the dermal tissue, providing deep hydration and stimulating the production of collagen, elastin and even adipocyte viability. The standard protocol is 2 sessions separated by 4 weeks, with maximum effect visible 2 months after the second session. Skinboosters—such as Restylane Skinbooster and Juvéderm Skinvive—use low or non-cross-linked HA injected into the superficial dermis through multiple micro-injections. Their goal is to hydrate, improve texture and provide luminosity without modifying facial volumes. Duration: Profhilo, approximately 6 months per cycle. Skinboosters, 4-6 months with maintenance sessions.

PDRN and polynucleotides

Polynucleotides (PN) and PDRN (polydeoxyribonucleic acid) are fractions of DNA of biological origin (usually from salmon) that act as tissue regenerators. Rejuran (Pharmaresearch) and Remedium are representative products. Their mechanism includes stimulation of fibroblasts, promotion of collagen synthesis, improvement of skin elasticity and a documented anti-inflammatory effect. Unlike HA biomodelers, polynucleotides work at the level of deep cellular repair and reconstruction of the skin barrier. The typical protocol requires 3 to 4 sessions separated by 2 to 3 weeks. Results are progressive and manifest in better texture, firmness and reduction of fine lines. Duration: effects accumulate with sessions; maintenance is usually recommended every 3-6 months.

Polyrevitalization: NCTF

NCTF 135 HA (Fillmed/Filorga) is an injectable polyrevitalization solution that contains free hyaluronic acid (non-cross-linked, 5 mg/ml) combined with 60 active ingredients: 12 vitamins, 24 amino acids, 6 coenzymes, 6 minerals, 5 nucleosides and glutathione. This formula creates an optimal cellular environment for fibroblast activity and natural collagen stimulation. It is injected intradermically and the usual protocol consists of 3 sessions every 3 weeks, followed by periodic maintenance. NCTF is positioned as a global revitalization treatment—improving skin density, luminosity, hydration and texture—rather than as a filling or remodeling product.

Autologous fat (lipofilling)

Lipofilling uses the patient's own fat, extracted via liposuction and processed before being re-injected into the face or body. It is the only "filler" completely autologous—it does not involve synthetic or external materials. Its advantage is complete biocompatibility and the possibility of permanent graft integration. Its disadvantage: it requires a surgical procedure (extraction + processing + injection), graft reabsorption is variable (30-50% of volume can be reabsorbed) and results are less predictable than with manufactured fillers. Lipofilling is not part of the office treatments that are usually associated with fillers, but deserves mention as an alternative within the complete spectrum of filling materials.

Comparative table of types of fillers

Where are fillers applied?

Fillers are applied in multiple areas of the face and body, and the choice of product depends on the specific anatomy of each area.

Lips

Lips require soft and flexible products that allow natural movement. Low to medium cross-linked HA fillers are used to increase volume, define the vermilion border, correct asymmetries or hydrate lip tissue. Products such as Juvéderm Volbella, Teoxane RHA Kiss or Restylane Kysse are specifically formulated for this area.

Cheekbones and middle third

The malar area requires products with high projection and support capacity. High cross-linked HA fillers (Juvéderm Voluma), CaHA (Radiesse) or biostimulators are used to recover the zygomatic arch and restore the structure of the middle facial third.

Jawline and chin

Defining the mandibular contour and projecting the chin requires firm gels with high cohesivity. Juvéderm Volux is specifically designed for this indication. CaHA and hybrids such as HarmonyCa are also used in this area.

Nasolabial folds and marionette lines

These deep creases are treated with medium to high cross-linked HA fillers or CaHA, injected in the subdermal or supraperiosteal plane to smooth the fold without creating an artificial appearance.

Periorbital area (dark circles)

The infraorbital region is one of the most delicate. It requires low cross-linked HA products, low hygroscopicity and predictable behavior, such as Teoxane Redensity 2 or Restylane Eyelight, applied by doctors with specific experience in this area.

Temples

The temples become hollowed with age due to loss of fat and temporal bone. They are restored with high cross-linked HA or CaHA in a deep plane.

Hands

The back of the hands loses subcutaneous tissue, revealing tendons and veins. Radiesse has specific FDA approval for rejuvenation of the back of hands. HA fillers are also used.

Neck and décolletage

These areas respond well to biostimulators (diluted Radiesse, Sculptra) and biomodelers (Profhilo, skinboosters, polynucleotides) to improve skin quality, reduce fine lines and provide firmness without volume.

Reversibility and safety

Reversibility is one of the most important factors when choosing a filler. Only hyaluronic acid fillers are reversible through the injection of hyaluronidase, an enzyme that degrades cross-linked HA and dissolves it within hours. This applies both to elective situations (correction of asymmetries, product excess) and to vascular emergencies.

Why does reversibility matter?

Vascular occlusion—when the filler compromises the blood flow of an artery or arteriole—is the most feared serious complication in aesthetic injectables. If the material is HA, rapid administration of hyaluronidase in the affected area can dissolve the product and restore tissue perfusion, preventing skin necrosis. In extreme cases (retrograde injection toward the ophthalmic artery), timely intervention can be determinative for preserving vision. Fillers made of CaHA, PLLA and PCL are not reversible with any enzymatic agent. Once injected, only the body's natural metabolism can degrade them over time. This does not make them unsafe—they have years of clinical use with well-documented safety profiles—but it does require greater precision in the injection technique and a thorough knowledge of facial vascular anatomy.

The importance of the injector

The product is only part of the equation. The training of the injecting physician is equally determinant for safety:

• Anatomical knowledge: identifying the location, depth and variations of the main blood vessels of the face.
• Injection technique: use of cannulas (which reduce the risk of vascular puncture), slow injection at low pressure, small volumes per point.
• Ability to manage complications: immediate availability of hyaluronidase, early recognition of ischemic signs (blanching, disproportionate pain, slow capillary filling), emergency action protocols. A certified aesthetic physician with specific training in injection anatomy and complication management offers a safety margin that no product alone can substitute.

Regulation of fillers: FDA, COFEPRIS, EMA and more

Dermal fillers are regulated as medical devices in most regulatory frameworks, not as drugs (unlike botulinum toxin, which is regulated as a biological drug).

FDA (United States)

The FDA classifies dermal fillers as Class III medical devices with product code LMH (dermal implant for facial aesthetic use) and PKY (dermal implant for aesthetic use on hands). They require pre-market approval (PMA) based on controlled clinical trials. The FDA approves each product for specific anatomical indications: approval for nasolabial folds is not the same as approval for lips, cheeks or chin.

EMA / AEMPS (Europe)

In the European Union, dermal fillers are regulated as medical devices under MDR Regulation 2017/745 and bear the CE mark. The AEMPS (Spanish Agency for Medicines and Health Products) supervises post-market surveillance in Spain.

COFEPRIS (Mexico)

In Mexico, COFEPRIS regulates fillers as medical devices. Products must have a valid health registration. It is the physician's responsibility to verify that the product used has COFEPRIS registration and verifiable chain of custody.

ANVISA (Brazil) and INVIMA (Colombia)

ANVISA in Brazil and INVIMA in Colombia follow similar frameworks, classifying dermal fillers as medical devices that require prior health registration before marketing.

How to verify that a product is legitimate

• Request from the doctor the exact trade name, manufacturer and batch number of the product.
• Confirm that the product has current registration with your country's regulatory agency.
• Verify that the syringe is opened in front of the patient and that the packaging is intact with authenticity holograms (when applicable).
• Be suspicious of prices significantly below market: original products have established manufacturing and distribution costs.

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Frequently asked questions

What are fillers?

Fillers are injectable substances applied under the skin to restore volume, smooth wrinkles or improve skin quality. The term encompasses a broad family of products with different materials and mechanisms of action. Although the word "filler" is translated as "filler," today it includes not only classic volumizing fillers (hyaluronic acid, calcium hydroxyapatite), but also collagen biostimulators (Sculptra, diluted Radiesse) and skin biomodelers (Profhilo, skinboosters, polynucleotides). They are applied by an aesthetic physician using a needle or cannula, usually at the office and with topical or local anesthesia. The procedure usually lasts between 15 and 45 minutes depending on the areas treated.

What are facial fillers?

Facial fillers are injectable fillers designed and approved specifically for use on the face: lips, cheekbones, chin, jawline, nasolabial folds, temples and periorbital area, among other areas. Each area of the face has distinct anatomical characteristics—skin thickness, proximity to blood vessels, degree of mobility—that determine which type of product is most appropriate. For example, lips require soft and flexible gels, while the jawline needs products with high projection capacity. The FDA approves each facial filler for specific anatomical indications, which means that not all fillers are authorized for all areas.

How long do fillers last?

Duration varies depending on the material: hyaluronic acid fillers last between 6 and 18 months, calcium hydroxyapatite 12 to 18 months, polylactic acid up to 25 months and polycaprolactone more than 2 years. In addition to the material, other factors influence duration: the treated area (areas with greater movement such as lips degrade the product faster), the patient's individual metabolism, the injection technique, the plane of placement and the amount of product. Biomodelers such as Profhilo last approximately 6 months per cycle, and skinboosters between 4 and 6 months. In all cases, a maintenance plan is recommended to prolong results over time.

What types of fillers exist?

There are at least seven main materials used in aesthetic injectables: hyaluronic acid, calcium hydroxyapatite, polylactic acid, polycaprolactone, hybrid combinations (CaHA + HA), polynucleotides/PDRN and autologous fat. These materials are functionally grouped into three categories: volumizing fillers (provide immediate volume), biostimulators (stimulate gradual collagen production) and biomodelers (improve overall skin quality without adding volume). Some products belong to more than one category depending on how they are used—for example, Radiesse can function as a filler in standard concentration or as a biostimulator when diluted. The choice depends on the goal of the treatment, the area to be treated and the preferences of the patient and their physician.

Are fillers dangerous?

Fillers approved by regulatory agencies (FDA, EMA, COFEPRIS, ANVISA, INVIMA) have well-documented safety profiles when applied by a trained physician. They are not high-risk procedures, but are not without complications. The most common side effects are mild and temporary: redness, swelling, bruising and sensitivity in the injection area, which usually resolve in days. Serious complications—such as vascular occlusion—are infrequent (estimated at 1 in 100,000 treatments) but potentially serious. That is why it is essential that the injector be a physician with specialized training in facial vascular anatomy, with hyaluronidase available and knowledge of emergency protocols. The greatest risks are associated with unapproved products, injectors without medical training and environments without safety standards.

What is the difference between fillers and botox?

Fillers and botox act through completely different mechanisms. Botox (botulinum toxin) is a neuromodulator that temporarily relaxes muscles to smooth expression wrinkles; fillers are materials injected into tissue to provide volume, stimulate collagen or improve skin quality. In clinical practice, they are complementary treatments. Botox is used mainly in the upper third of the face (forehead, brow, crow's feet) where wrinkles form from repeated muscle contraction. Fillers are used predominantly in the middle and lower third (cheekbones, wrinkles, lips, chin, jawline) where the problem is volume loss, sagging or lack of definition. Many treatment plans combine both for comprehensive results.

What is the difference between a filler and a biostimulator?

A filler provides immediate volume to the tissue where it is injected; a biostimulator activates fibroblasts to produce new collagen gradually over weeks or months. With a hyaluronic acid or concentrated CaHA filler, the patient leaves the office with the visible result (which is refined in the following days as swelling decreases). With a biostimulator such as Sculptra or diluted Radiesse, the effect is progressive: the first improvements are noticed in a few weeks and the final result is seen between 3 and 6 months. Biostimulators usually require more than one session but offer longer-lasting and more naturally-looking results, since the volume comes from the patient's own collagen.

Are fillers reversible?

Only hyaluronic acid fillers are reversible. Hyaluronidase, an injectable enzyme, degrades cross-linked HA and dissolves the filler within hours. Calcium hydroxyapatite, polylactic acid and polycaprolactone fillers are not reversible with any enzymatic agent: they degrade only through natural metabolism over months. This difference is clinically relevant: in case of vascular complication with HA, hyaluronidase allows for immediate emergency intervention. With non-reversible fillers, management of vascular complications is more complex and depends on vasodilators and other support measures. For this reason, many physicians recommend starting with HA fillers, especially in new patients.

What is Profhilo?

Profhilo is a biomodeler injectable of ultrapure hyaluronic acid with high concentration (64 mg/2 ml), manufactured by IBSA using NAHYCO technology without chemical cross-linking agents. Unlike volumizing fillers, Profhilo does not add volume or modify facial contours. It is injected at 5 strategic points per hemiface and diffuses through dermal tissue, providing deep hydration and stimulating collagen and elastin production. The standard protocol consists of 2 sessions separated by 4 weeks. The result—firmer, hydrated and more luminous skin—reaches its maximum expression approximately 2 months after the second session and lasts about 6 months. It is especially useful for skin with loss of elasticity, fine lines and dull appearance.

What is Sculptra?

Sculptra is a collagen biostimulator based on poly-L-lactic acid (PLLA), manufactured by Galderma. It is not a conventional filler: it does not provide immediate volume, but stimulates the gradual production of the patient's own collagen. Once injected, PLLA microparticles generate a biological response that activates fibroblasts. New collagen forms progressively over months, with visible results between the second and sixth month after each session. The typical protocol includes 2 to 3 sessions separated by 4 to 6 weeks. Results can last up to 25 months. Sculptra is FDA approved for correction of nasolabial folds and facial lipoatrophy, and is widely used to restore volume in patients with moderate to severe tissue loss.

At what age can fillers be placed?

There is no universal minimum age for fillers, but regulatory agencies such as the FDA approve most dermal fillers for patients over 21 years old. The indication is based on clinical need, not on a number. In practice, patients seeking volumizing fillers are usually between 30 and 60+ years old, when loss of facial fat, bone and collagen generates visible changes. However, some indications—such as lip augmentation, correction of marked congenital dark circles or scar improvement—may be appropriate in younger patients. Biomodelers and skin quality treatments can begin around 25-30 years old as a preventive strategy. The decision should always be made in consultation with a physician who evaluates individual anatomy, expectations and cost-benefit relationship.

What is a biomodeler?

A biomodeler is an injectable designed to improve overall skin quality—hydration, elasticity, luminosity and firmness—without adding volume or modifying facial contours. Biomodelers work by stimulating natural skin repair and regeneration processes at the dermal level. Profhilo, the most well-known, uses high and low molecular weight hyaluronic acid to hydrate and stimulate collagen and elastin. Skinboosters (Restylane Skinbooster, Juvéderm Skinvive) hydrate the superficial dermis through HA micro-injections. Polynucleotides/PDRN (Rejuran, Remedium) promote tissue regeneration at the cellular level. All share a common goal: to improve the skin "base." They are ideal as a complement to volumizing fillers or as an independent treatment for skin that needs revitalization without structural changes.