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Non-Hyaluronic Acid Dermal Fillers: Types & Complications
Non-Hyaluronic Acid Dermal Fillers

Non-hyaluronic acid dermal fillers

Some dermal fillers do not contain hyaluronic acid. For example, calcium hydroxylapatite (CaHA), Poly-L-lactic acid (PLLA), collagen, and polymethylmethacrylate (PMMA).

1. Polymethylmethacrylate (PMMA)

PMMA is formulated as non-absorbable microspheres. Once administered into the subdermal layer, it stimulates fibroblasts, thereby encapsulating the microspheres and augmenting the volume of tissues through fibroplasia.

Artefill contains PMMA suspended in bovine collagen. Being the only PMMA filler approved by the FDA, Artefill is indicated for the treatment of acne scars and nasolabial folds. However, earlier versions of the filler have been reported to cause granuloma formation, with a high incidence rate of 2.5%. Some patients may be allergic to bovine collagen; therefore, it is advisable to perform skin testing before the injection.

2. Poly-L-lactic acid (PLLA)

PLLA is a type of absorbable polymer that promotes collagen regeneration and fibroblast synthesis. The results of poly-L-lactic acid can typically last for 2 years. For best results, patients are required to undergo several treatment sessions. A potential complication of PLLA is the development of palpable nodules. However, Woerle et al has suggested that the incidence rate of nodule formation can be reduced to less than 1% with proper precautions in place. This includes addition of lidocaine, longer hydration time, proper handling of the vials, and adequate dilution. Alessia et al has made similar recommendations. Sculptra is the only FDA-approved dermal fillers that contain PLLA. Since 2004, it has been used for the treatment of facial lipoatrophy in HIV (human immunodeficiency virus) patients.

3. Collagen

Collagen can be sourced from human donors, bovine or porcine. Collagen dermal fillers are commonly mixed with gel carriers such as PMMA. Collagen-based fillers have been approved for the treatment of wrinkles and scars. They can also be used to correct facial contours and deep folds.

4. Calcium hydroxylapatite (CaHA)

To date, there is only 1 calcium hydroxylapatite dermal filler that has obtained approval from FDA, which is Radiesse. Approved in 2006, Radiesse is indicated for the treatment of skin folds and wrinkles of moderate severity. Similar to PLLA, it is used for the treatment of facial lipoatrophy in HIV patients. Containing 30% of calcium hydroxylapatite microspheres in a 70% gel carrier suspension, Radiesse is a man-made compound which is similar to the teeth and bone structures. No patch testing is required before the treatment, as Radiesse is not known to cause any immunogenicity reaction. The results of Radiesse can last for up to a year.

Other dermal fillers

Practitioners may be aware of hyaluronic acid dermal fillers and other classes of commonly-used, FDA-approved fillers. However, there are many other types of less commonly used fillers. This includes agarose gel, polyacrylamide gel, dextran particles, autologous fat transfer, and polycaprolactone.

Considerations before a filler injection

While hyaluronic acid fillers are generally safe and well tolerated, they have a risk of causing undesirable effects. As a precaution, practitioners should identify any contraindications that may make dermal fillers unsafe to use. HA dermal fillers are contraindicated in patients with known hypersensitivity to hyaluronic acid (or other components in the formulations such as lidocaine) and an active infection at the treatment site.

In order to ensure patient safety, practitioners should identify factors that can potentially affect the treatment outcomes and recovery time. This includes psychological conditions such as anxiety, depression and body dysmorphia. Prior to the treatment, doctors should also check if the patient has diabetes, dermatological problems, autoimmune diseases, immunosuppressive or any other diseases that may affect the patient physically.


As with all other interventions, hyaluronic acid fillers may sometimes cause complications even if they are used correctly. Apart from common side effects such as skin swelling, bruising, and redness, dermal fillers may also cause rare but severe adverse effects such as infection and granulomatous inflammation. While uncommon, fungi, viruses, and bacteria can potentially cause infections after a filler injection.

Abnormal tissue reactions may cause granulomatous inflammation or the formation of nodules. Mediated by T cell or macrophage interaction, granulomatous inflammation belongs to the type 4 hypersensitivity reaction. Some of the pharmacological treatments of granulomatous reactions include topical 5-florouracil, triamcinolone acetonide injection, and cortisone injection. Surgical incision may be needed in some cases. While extremely rare, the use of HA dermal fillers may result in an anaphylactic reaction, which is a potentially life threatening. Prompt treatment may help to save patients’ lives. Therefore, practitioners who offer HA injections should undertake anaphylaxis management training on a regular basis. They should also have the equipment handy.

Arterial embolization (AE) that impedes arterial blood flow could disrupt the blood flow through tissue compartments. Subsequently, this may lead to ulceration, tissue necrosis, mottling, blanching, and pain. Other than that, some patients may experience embolism of fillers, which is known to cause serious consequences such as stroke, blindness and extensive necrosis.

The risk of intravascular filler injection can be minimized through the following methods:

1. Using a cannula with large diameter instead of a narrow needle. A cannula with a blunt tip and wide bore has a lower risk of piercing the blood vessels. This makes the aspiration process easier.

2. Perform aspiration before administration (even if the cannula or needle is primed with fillers). This helps to identify any blood flashback and hence the position of the needle tip in a blood vessel.

3. Inject the filler slowly to minimize the risk of intravascular injections and pressure damage.

4. Inject small aliquots of dermal fillers into a single area. Injecting a large volume of an injectable into the blood vessel can potentially be life threatening.

5. In general, it is safer to perform a retrograde injection than an anterograde injection. This is because retrograde injection is associated with a lower risk of intravascular injection.


Hyaluronic acid is a natural substance that can be found in the skin. To improve its performance, hyaluronic acid is often cross-linked using proteins (such as 1, 4-BDDE) during the manufacturing process. This increases the resistance of hyaluronic acid to decomposition, thereby increasing its duration of action. Most hyaluronic acid fillers are able to last for at least a few months in the skin. Hyaluronic acid dermal fillers vary greatly in terms of their rheological properties due to the different technologies used in the manufacturing process. The most appropriate dermal filler should be chosen based on the location of treatment. In addition to conventional hyaluronic acid fillers, there are many non-hyaluronic acid fillers that have a longer duration of actions. Plus, some of these fillers are able to promote collagen regeneration. To obtain optimal results, practitioners should use the most suitable dermal filler which has desired properties for a particular indication.

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