The dermal filler market size was valued at USD 5.01 billion in 2022 and is projected to grow from USD 5.32 billion in 2023 to USD 9 billion by 2030. This is an AGR of 7.8% during 2023-2030.

North America dominated the global market with a share of 41.91% in 2022.

The American Society for Aesthetic Plastic Surgery reported that 3,410,730 people got dermal filler in the year 2020 and the popularity continues to grow. This growth is fueled by the accessibility of fillers, the short recovery time and the instantaneous results that are obtained from this procedure.

Dermal fillers rank second in the invasive aesthetic procedures done in the world. The first is neuromodulation with agents such as Botox or Dysport.

What is the reason for this exponential use of fillers?

To combat aging of the skin and the quest for a youthful appearance. Human skin aging is the result of two independent processes. The first is intrinsic or innate aging, an unpreventable process which affects the skin as it does in all organ systems. Intrinsic aging is highly influenced by decreased production of sex hormones. This decrease causes collagen degradation, dryness, loss of elasticity, atrophy and wrinkling. The second is extrinsic aging, which is the result of exposure to our environment. Extrinsic aging is highly influenced by ultraviolet radiation, also called photoaging.

Both intrinsic and extrinsic skin aging share similar molecular mechanisms. Reactive oxygen species arising from oxidative cell metabolism is the common denominator. ROS induces transcription factor causing over expression of matrix metalloproteinase and this prevents the expression of procollagen. Therefore, elevated levels of degraded collagen and reduced collagen synthesis is the cause of aged skin.

Skin aging is associated with a loss of moisture. The key to skin moisture is hyaluronic acid which is a glycosaminoglycan which has the ability to bind and retain water. Hyaluronic acid resides in the extracellular matrix. It is now well documented by studies, the extracellular matrix is located between the layers of the skin. The molecules of the extracellular matrix provide framework but also exert major effects on cellular function. The form a highly organized structure comprised of glycosaminoglycans, proteoglycans, growth factors and structural proteins such as collagen. However, the major component of the extracellular matrix in skin is hyaluronic acid.

Hyaluronic acid is most abundant in the skin. This comprises 50% of the total volume in the body. Hyaluronic acid is produced primarily by mesenchymal cells. Although the main function of HA is hydration, it also functions in lubrication of the joints, space filling capacity and provides framework through which cells migrate. HA also has been implicated in several aspects

of tissue repair. It can activate inflammatory cells to enhance immune response. HA has been involved in activation of fibroblasts responding to tissue injury.

The size of the hyaluronic molecule appears to be of critical importance for its various functions. HA of high molecular size is present in normal tissue and is antiangiogenic and immunosuppressive while small size molecules are found in distress states and are potent inducers of inflammation and angiogenesis.

In aging of the skin, there is a marked reduction of epidermal HA while HA is still present in the dermis. The synthesis of HA in the epidermis is different and distinct from that of the dermis. Therefore, the epidermis loses the principal molecule responsible for the retention of water. As the moisture in the upper layers of the skin are lost, skin aging occurs.

Hyaluronic Acid Fillers

Hyaluronic acid-based fillers are the most common and popular dermal fillers used in aesthetic medicine. These fillers are hydrogels comprised of 95% water and .5-3% of hyaluronic acid. HA is a polysaccharide, and the structure of HA is identical among all living organisms. This property makes HA highly biocompatible versus certain protein based fillers(collagen) which can exhibit an amino acid sequence and can be recognized by the immune system as foreign.

The major limitation of HA when used as a dermal filler is the turnover within the tissues. This turnover is caused by hyaluronidases within the tissues. To increase the duration of the filler in the tissue, modifications have been added to reduce the ability of hyaluronidases to degrade the hyaluronic acid filler. This is called cross linking. This process yields a more resistant product to enzyme degradation due to the formation of bridges and covalent bonds between the cross-linking agent and hyaluronic acid.

The chemical cross-linking agents employed to produce cross linked hyaluronic acid include,

  • Methacrylamide hydrazide
  • Carbodiimide
  • Divinyl sulfone
  • 1,4 butanediol diglycidyl ether (BDDE)
  • Poly diglyidyl ether (ethylene glycol)

These agents have been used for decades and are known cytotoxic and in some cases mutagenic. Their residual presence in the final hydrogel must be closely monitored and in the case of the most widely used, BDDE, its residual concentration is thought to be safe below 2 parts per million.

An interesting detection of a new by product in BDDE cross-linked autoclaved hyaluronic acid hydrogels was found and published in 2018 by Javier Fidalgo.

He concluded the toxicity of this by product od BDDE is unknown. Since autoclaving procedures are usually employed for the sterilization of dermal fillers, the author believes that this detected product should be taken into account.

The most common describer for cross linked fillers is elastic modulus(G’). It is used to describe the firmness of the gel and represents the ability of a gel to resist an applied force. Generally, the higher the G’, the more volumizing and support. They also require deeper placement. As G’ increases, so does the cross linking needed to construct it. Restylane as the first HA-based filler approved for use in the US in 2003.

Galderma introduced new products in 2016. They classified these products based on flexibility and the amount of stretching the gel could withstand. Strain is used now as the index of flexibility and is inversely related to cross linking.

Bolero was introduced in 2011. This product uses a second cross linking stage with the addition of non-cross linked HA. This produces a cohesive yet smooth product.

Platelet Rich Plasma is an autologous blood product in which the platelet number is concentrated and greater than whole blood. In regenerative medicine, the platelets have many more functions than just blood clotting. The alpha granules contained on the platelets are rich in cytokines, growth factors and bioactive proteins. Upon activation, the alpha granules release their contents, and the regenerative process commences with the release of these signaling molecules.

Intra-articular injections of hyaluronic acid have been used and studied extensively in the musculoskeletal field. Intra-articular injections of HA result in the restoration of the overall properties of the synovial fluid and when used in combination with PRP, an increase in the biological activity is seen. This leads to more pronounced clinical outcomes. It has been found after investigation, the PRP/HA combination creates a bioactive scaffold around cells and the duration of the release of the growth factors and cytokines is increased.

Platelet Rich Fibrin is the second generation of platelet products. It is obtained by heating the PRP for 6 minutes and then cooling for 4 minutes. This process polymerizes the plasmatic proteins (albumin) forming a thermal aggregate cross linked with the fibrin network. This network does not use any chemical additives only the patient’s own blood.

At Juventix Regenerative Medical, we have added non cross-linked hyaluronic acid to the tubes and once processed, an injectable bio filler is obtained. This filler is devoid of any chemicals and is easily injected and used for regenerative purposes.

This combination of platelet rich fibrin and hyaluronic acid is a unique biomaterial, non-cytotoxic and suitable for cell growth due to the ability to release growth factors over time. Also, there is a nutritional function in this combination that is produced by the bioactive proteins.

Juventix Regenerative Medical is an industry leader in the regenerative medical field. Our Platelet Rich Plasma kits are FDA cleared and designed for safety, sterility and ease of use. Our kits are scientifically manufactured to produce a platelet concentrate, devoid of red blood cells with a minimal amount of leukocytes, critical to the regenerative process.

Juventix Regenerative Medical offers a LED Activator to activate the platelets and begin the regenerative process. The activation is a critical step in the release of cytokines, growth factors and bioactive proteins from the alpha granules on the platelets and is accomplished with LED light. This negates the use of chemical additives such as Calcium Chloride, Thrombin or Collagen. This mode of activation by LED light provides sustained growth factor release versus older methods of activation while adhering to the minimal manipulation standards recently released by the FDA.

Juventix Regenerative Medical supplies a bio-incubator to transform the Platelet Rich Plasma into an Injectable Platelet Rich Fibrin. The Platelet Rich Fibrin, commonly called the “second generation of platelet products” has different cytokines and growth factors than the original PRP. These different cytokines provide an anti-inflammatory environment and can be used confidently in inflammatory conditions.

Juventix Regenerative Medical provides a PRP kit than has non cross-linked hyaluronic acid included in the tube. When centrifuged, activated and finally placed into the bio-incubator, the final product is an all-natural injectable filler. This causes less side effects and does not have long term complications as the cross-linked filler.

Perhaps the choice is a chemically linked cross linked filler versus an all-natural filler. Thousands of aesthetic clients have already made the natural choice.



Regenerative Regards,

Dr. Robert McGrath



Bioengineering 2022 Dec 19;9(12):817 PMID 36551023

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Ont J Anal Chem 2022 May 23;2022;4565260 PMID 35651502

J Cosmet Dermatol 2022 Jan;21(1):191-198 PMID 34559948

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