Dermal fillers, among other types of cosmetic treatments, have rapidly grown in popularity over the past few years. With more than 92% of all dermal filler sales in the United States coming from fillers with hyaluronic acid as their base, it is clearly the most widely used ingredient. This article will cover a variety of topics related to hyaluronic acid dermal fillers, including their use, regulation, and general physical characteristics. We’ll also look at some additional classes of FDA-approved dermal fillers, which are based on other key ingredients.
Hyaluronic Acid Present In The Human Body
A substance called hyaluronic acid occurs naturally in every part of the human body. It is made up of a lengthy, linear polysaccharide made up of repeated N-acetylglucosamine and glucuronic acid disaccharide units. Importantly, the length of hyaluronic acid polymers varies, which affects their weight. The weight of the hyaluronic acid chain affects their behavior and properties within human tissue.
The skin contains about 50% of the total amount of hyaluronic acid in the human body. Hyaluronic acid serves as the extracellular matrix’s scaffold or structure in the skin, giving it hydration, turgor, and rigidity while also enabling cellular movement and regeneration. Additionally, hyaluronic acid shields the skin from free radical damage, especially from UVA and UVB rays. Interestingly, a third of the body’s total volume of hyaluronic acid is recycled every day as a result of the fast metabolism and high turnover rate of hyaluronic acid in the tissue.
The balance between hyaluronan synthases, such as HAS1, HAS2, and HAS3, and hyaluronidases, such as HYAL1, HYAL2, and HYAL3, controls the body’s levels of hyaluronic acid. In cosmetic treatments, hyaluronidases (such as Liporase) can be used to successfully undo the effects of hyaluronic acid filler treatments because of their capacity to degrade hyaluronic acid.
Hyaluronic Acid-based Dermal Fillers
Long hyaluronic acid chains that are typically cross-linked with substances like 1,4-butanedioldiglycidyl ether (BDDE) for Restylane, Belotero, and Juvederm; 1,2,7,8-diepoxyoctane (DEO) for Puragen; or divinyl sulfone (DVX) for Hylaform; are made up of hyaluronic acid dermal fillers. The product is then processed as either a homogeneous gel or a suspension of particles contained within a gel carrier.
There is a remarkable variety of fillers available, each with different properties in terms of particle size, degree of cross-linkage, and concentration, as different manufacturers have different methods to produce their dermal filler gels. The clinical effectiveness of the various dermal fillers is determined by these physical characteristics.
Hyaluronic acid fillers can be categorized according to their different particulate forms. Hyaluronic acid is mixed and cross-linked in a single step in monodensified gels like Juvederm and Teosyal, which are a subset of monophasic gels. In addition, hyaluronic acid undergoes two stages of cross-linking in polydensified gels like Belotero dermal fillers. Hyaluronic acid is divided into two phases in biphasic gels; typically, cross-linked hyaluronic acid is suspended with non-cross-linked hyaluronic acid, which acts as a carrier.
The superiority of one gel type over the other is hotly debated in aesthetic literature and among practicing doctors. It is more likely, though, that neither approach is actually superior to the other in all situations. Instead, some fillers are better suited for particular cases because different therapeutic indications will influence how desirable a filler’s physical characteristics are.
Dermal Filler Rheology
The performance of a specific product is greatly influenced by the rheological properties of a dermal filler, or the characteristics that affect how the material responds to outside forces. Dermal fillers are subjected to external pressures after being implanted, including vertical compression and stretching pressure from facial muscle movement, as well as shearing, compression, and gravity. To successfully tailor and choose the best filler for achieving the best results, practitioners must be aware of how dermal fillers will react when injected into a patient’s particular area or skin layer.
For various facial areas, very different dermal filler properties are preferred. For example, the very deep subdermal layers of the cheeks are best treated with a dermal filler that has volumizing properties. On the other hand, spreadability of the filler is more highly valued when injecting it into superficial layers so that it can seamlessly bind with the tight connective tissue present in the top layers of the skin.
The various rheological characteristics of a dermal filler are measured using a wide range of different variables. These consist of:
- The filler’s complex modulus (G*), also referred to as its hardness, measures how challenging it is to change the filler’s shape.
- Elastic modulus (G’): A measurement of the stiffness and resistance to deformation of a dermal filler under external pressure.
- Cohesivity: A filler’s comparatively strong lifting ability. The level of cross-linking and hyaluronic acid concentration are the two main factors that affect cohesiveness.
- The filler’s inability to regain its shape after the shear stress is removed is known as its viscous modulus (G”).
Here’s how different treatment areas align with the desired physical properties of dermal filler formulas:
In order to restore volume, fillers are injected deeply or sub-dermally into the cheeks. Therefore, a dermal filler that can withstand shear deformation and compression with little displacement and the ability to maintain its shape is ideal in this area. The dermal filler should be extremely elastic and have low viscosity to make injection easier in order to accomplish these goals. The cohesivity of suitable dermal fillers should be between medium and high. Juvederm Voluma, Belotero Volume, Restylane Lyft, Teosyal Ultra Deep, and Teosyal Ultimate are a few examples of these dermal fillers.
Lips and Fine Lines
The dermal filler used for these indications should be able to successfully restore volume at the intradermal and subdermal levels. It should be easily spreadable and volumizing without adding excessive bulk. Low viscosity, elasticity, and cohesivity profiles are desirable in dermal fillers for these areas. Dermal fillers like Juvederm Volbella, Teosyal RHA 2, Restylane Kysse, Restylane Refyne, and Belotero Balance are a few examples of those that fit this description.
Dermal fillers used to restore facial volume in the lower face are injected into the deep dermal or subdermal planes. The ideal dermal filler should have no palpable projection, be highly moldable, and be spreadable. For these uses, a dermal filler should have moderate elasticity, low-medium cohesivity, and low viscosity as desirable rheological characteristics. These qualities can be found in dermal fillers like Teosyal RHA 3, Juvederm Volift, Restylane Refyne, and Belotero Intense.
Treatments for the chin and nose are typically used to reduce nasal and chin projection. As a result, the dermal filler should provide the greatest possible vertical projection while having the least amount of lateral spread. For ease of injection, a filler for the nose and/or chin should have low viscosity, high elasticity, and high cohesivity. Belotero Volume, Restylane Lyft, Juvederm Voluma, and Teosyal Ultimate are a few examples of these dermal fillers.
Non-Hyaluronic Acid Fillers
There are also dermal fillers made of substances other than hyaluronic acid that have their own efficacy and safety profiles. Let’s review a few of these fillers and their various unique qualities.
Calcium Hydroxylapatite (CaHA)
CaHA fillers, sold under the trade name Radiesse, were initially authorized for the treatment of facial lipoatrophy in HIV patients as well as the eradication of mild wrinkles and skin folds1. 30% calcium hydroxylapatite microspheres suspended in a 70% gel carrier make up this dermal filler. The filler’s calcium derivative is the same substance that makes up human bones and teeth. Radiesse is therefore non-immunogenic. Results from this dermal filler last for roughly 12 months.
Poly-l-lactic Acid (PLLA)
PLLA stimulates the production of collagen by fibroblasts, with effects that typically last up to two years. To achieve the best results, this treatment requires a number of sessions. There have previously been issues with this dermal filler’s tendency to delay the development of palpable nodules. However, numerous studies have produced recommendations that lower the likelihood of nodule formation. These recommendations include a longer hydration time, adequate dilution, the addition of lidocaine, and proper vial handling. PLLA fillers, marketed as Sculptra, were initially FDA-approved in the US in 2004 for the treatment of facial lipoatrophy in HIV patients2.
Dextran particles, fat transfer, polyacrylamide gel, polycaprolactone, and agarose gel are some additional, less popular dermal fillers. Although all of these dermal fillers have FDA approval, they are not as well known or utilized as the other fillers mentioned above.
Considerations Before Treatment
Injections of dermal fillers made of hyaluronic acid are not appropriate for all patients. Patients with ongoing infections or those who have a history of dermal filler or other product ingredients, like lidocaine, hypersensitivity are also included.
Patients who have risk factors that could affect their treatment and recovery should also be found and given more attention. Patients who fit into this category have both psychological and physical conditions, such as body dysmorphia, anxiety, or depression. Physical conditions include immunosuppression, dermatological issues, autoimmune disorders, or diabetes.
There is a chance of complications with all fillers. Patients should be made aware of more serious potential risks in addition to the anticipated injection-related side effects of redness, swelling, and bruising. For instance, even though infections following dermal filler therapy are uncommon, they can be extremely dangerous if they do.
Occasionally, an abnormal tissue reaction to treatment can lead to nodule formation or granulomatous inflammation. Cortisone, triamcinolone acetonide, or topical 5-florouracil injections are the recommended treatments for these unintended consequences. In some cases, surgical excision may also be appropriate. Anaphylactic reactions are another side effect to be cautious of. Although they are usually uncommon, these are very serious. Rapid intervention can save the lives of anaphylactic patients, so it is crucial that injectable procedure providers are trained in anaphylaxis and have the necessary safety supplies on hand at all times.
By accidentally injecting a filler into a blood vessel, injectable dermal fillers can result in vascular compromise, which disrupts blood flow through a tissue compartment. Serious effects include blanching, pain, mottling, tissue ulceration, and necrosis as a result. There have also been reports of embolization, which can result in side effects like blindness, severe necrosis, and stroke.
By adhering to these recommendations, the risk of vascular compromise can be reduced:
- Using a cannula instead of a needle. The wider diameter of the blunt-tip cannula is far less likely to pierce through a blood vessel and is better to aspirate.
- Before injecting, practice aspiration with a needle.
- Only apply a small amount of the dermal filler to a single area. When large amounts enter a blood vessel, the patient may die.
- Dermal filler is injected retrograde as opposed to anteriorly. Intravascular injection is less likely following retrograde injection.
- Dermal filler is injected gradually to minimize pressure damage.
The characteristics of hyaluronic acid make it suitable for use. Hyaluronic acid must be stabilized, usually through modification via cross-linking proteins like 1,4-BDDE, to make it a useful soft tissue augmentation agent. Hyaluronic acid becomes more resistant to deterioration as a result, extending the effectiveness of its effects.
Hyaluronic acid dermal fillers are produced using a variety of technologies, and as a result, a wide range of rheological and physical properties are now available on the market. Dermal fillers now come in a variety of types, which gives practitioners a wide range of options to choose from depending on the specific aesthetic indication. This enables them to get the best care and results for their patients by optimizing and customizing the treatment.
 FDA. Dermal Fillers Approved by the Center for Devices and Radiological Health, (2018) https://www.fda.gov/medical-devices/aesthetic-cosmetic-devices/fda-approved-dermal-fillers
 Lisa C. Kates, and Rebecca Fitzgerald, Poly-L-Lactic Acid Injection for HIV-Associated Facial Lipoatrophy: Treatment Principles, Case Studies, and Literature Review (2008) https://pubmed.ncbi.nlm.nih.gov/19083552/