Hyaluronic Acid: Applications and Molecular Characteristics
Hyaluronic Acid (HA) is a naturally occurring glycosaminoglycan with applications in medical aesthetics and osteoarthritis. These is a huge difference between the hyaluronic acid used in aesthetic applications as a filler versus osteoarthritic joint treatments.
Hyaluronic Acid as a Facial Filler
Hyaluronic acid is a high molecular weight polysaccharide composed of repeating disaccharide units of glucuronic acid and N-acetylglucosamine. It is abundantly present in human connective tissues, skin and synovial fluid. It has significant viscoelastic properties and a strong capacity to retain water making it unique in cosmetic applications.
In cosmetic dermatology, HA is utilized as a dermal filler for the treatment of volume loss and facial wrinkles. The efficacy of HA filler is significantly influenced by the molecular weight which affects the gel’s viscosity, elasticity and tissue integration.
Hyaluronic acid fillers have a molecular weight ranging from 500,000 to 6 million Daltons. The higher the molecular weight, the longer lasting. Also, the hyaluronic acid used for fillers is chemically cross-linked providing longer lasting effects and stability where it is applied.
Hyaluronic Acid as a Osteoarthritis Treatment
In the management of osteoarthritis, HA serves as a viscosupplement to restore the cushioning and lubrication in the joint space that was lost in the disease state. HA reduces pain and restores joint normal physiologic function. The molecular weight of these products can vary but usually between 750,000 and 1 million Daltons. Studies have shown MW between 850,000 and 2.3 million Daltons offer effective pain relief and have a prolonged duration of action. The choice of the molecular weight is critical as it influences the HA’s ability to integrate into the joint environment and modulate the inflammatory process.
What is a Dalton?
Molecular weight, also known as relative molecular mass, is the sum of all the atoms in a molecule. It is used to measure the size of a molecule and is typically expressed in Daltons or atomic mass units.
Calculating the molecular weight of hyaluronic acid is complex because it is a high molecular weight polysaccharide made up of disaccharide units. The molecular weight depends on the chain length i.e. the number of disaccharide units.
Production of Hyaluronic Acid
HA is produced by two methods. The two methods are from animal extraction and microbial fermentation. Historically, animal derived HA came from the rooster combs but due to concerns over immunogenicity and disease transmission, microbial fermentation has evolved into the preferred method. This method involves culturing bacteria such as Streptococcus zooepidemicus to produce HA. The HA is then harvested and purified removing proteins and endotoxins. The resulting pharmaceutical grade HA is then ready for medical applications.
The molecular weight is a critical determinant of its functional properties.
Incompatibility of Facial Fillers and HA for Joints
HA formulations designed for facial fillers are chemically cross linked to achieve specific properties for soft tissue augmentation. This cross-linking process results in a dense gel with a high molecular weight enhancing the filler’s effects in volumizing an area and enhances the longevity in that location. However, when injected into joints, such dense formulations disrupt the natural viscoelastic properties of the synovial fluid leading to altered joint mechanics and inflammatory reactions.
Molecular Weight in Different Applications
Facial Fillers
- Typically, 1 to 6 million Daltons.
- These fillers are chemically cross linked to increase longevity, volume retention and resistance to degradation.
- Cross linking makes the HA denser and gel like, ideal for staying in place.
Knee Injections for Osteoarthritis
- Low molecular weight 500,000 to 730,000 Daltons (Hyalgan)
- Intermediate 800,000 to 2 million Daltons
- High molecular weight 2 to 6 million Daltons (Synvisc)
It should also be noted Synvisc is partially cross linked, but the goal is still mimic natural synovial fluid and not create a still gel.
Why Can’t Facial Fillers Be Used in the Knee?
Cross Linking and density.
- Facial fillers are heavily chemically cross linked forming a stable gel like material that stays localized in soft tissue and resists migration.
- Knee viscosupplemention products are not cross linked so they can diffuse throughout the joint and aid in the lubrication and cushioning.
Therefore, facial fillers are for volume and structure. Knee injections are for lubrication, cushioning and anti-inflammatory effects.
What Happens If You Inject Facial Filler Into a Joint?
Cross linked high molecular weight facial fillers cannot flow naturally in the joint space.
The body recognizes this foreign material as abnormal and triggers joint swelling, pain, inflammatory reactions and painful reduced movement. Complications of facial fillers placed into a joint space include, joint effusion, severe inflammation which may be chronic, granuloma formation and joint infection risk. Even if the above did not occur, there would be little to no therapeutic benefit and potentially could worsen symptoms if placed into a joint.
Comparison of Hyaluronic Acid Products
Juvederm Voluma Facial Filler @-3 million Daltons, high cross linking, Used for deep volume.
Restylene Facial Filler @ 1-2 million Daltons, high cross linking , Mild to deep usage
Belotero Facial Filler @1-2 million Daltons, moderate cross linked, Used for fine lines.
Hyalgan. Knee @ 500-700K Daltons, not cross linked, low viscosity
Orthovisc Knee @ 1-2 million Daltons, not cross linked, moderate viscosity
Aurhors note: I have used all currently available products for viscosupplemention with significant success. However, I have not had a significant response with Synvisc. Possibly, because it is partially cross linked and the Dalton weight for Synvisc One is 6 million.
Safety Issues with Cross Linking
Cross linking of hyaluronic acid in dermal fillers is done using a chemical process to enhance the durability and longevity of the filler when placed in the skin. Cross linking makes it more resistant to enzymatic degradation.
The most common linking agent is 1,4-Butanediol diglycidyl ether (BDDE). In its pure form, BDDE is considered toxic and has proven mutagenic activity. The FDA admits to the carcinogenic potential of pure BDDE but allow trace amounts in the final product used for fillers. Divinyl sulfone is another cross-linking agent, more reactive and used less frequently due to higher potential toxicity.
Other agents being investigated include Polyethylene glycol diglycidyl ether (PEGDE). While pure cross-linking agents are toxic and carcinogenic, the FDA has deemed small amounts of the chemicals can be used in fillers.
Authors note: What happens when people use these fillers for years? Food for thought!
Conclusion: HA Fillers and Joint Injections Are Not Interchangeable
In conclusion, hyaluronic acid fillers used in facial aesthetics cannot be used in musculoskeletal joint applications due to their heavy molecular weight and their chemical cross-linked properties.
About Juventix Regenerative Medical and PRP Innovations
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 effectiveness. Our kits are scientifically manufactured to provide a platelet concentrate, devoid of red blood cells with a minimum number of leukocytes that are critical for the regenerative process.
LED Platelet Activation Without Chemicals
Juventix Regenerative Medical offers a patented LED Activator to activate the platelets and begin the regenerative process. The activation is a critical step in the release of growth factors, cytokines and bioactive proteins from the granules that are contained 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 of the FDA.
This activation should always be accomplished after a gentle swirl of the centrifuged product to maximize the number of captured platelets.
Platelet-Rich Fibrin Creation Using the Juventix Bio-Incubator
Juventix Regenerative Medical supplies a patented Bio-Incubator to transform the Platelet Rich Plasma into an Injectable Platelet Rich Fibrin which can be used as a facial filler. The Platelet Rich Fibrin, commonly called “the second generation of platelet products” has different cytokine and growth factors than the original platelet rich plasma. These different cytokines provide an anti-inflammatory microenvironment and can be used confidently in inflammatory conditions.
Natural Fillers Without Cross-Linked HA or Toxicity
Juventix Regenerative Medical has Platelet Rich Plasma Kits that contain non-cross-linked hyaluronic acid. Once placed in the Bio-Incubator, the resulting product is a safe, sterile and effective alternative when used as a natural filler. Since chemical cross linking is not used in the hyaluronic acid contained in the tube, the toxic and possible carcinogenic potential does not exist even when used in repeated applications. However, the molecular weight is extremely high, and this specialized kit, should never be used in any joint applications for osteoarthritis as a significant inflammatory reaction will ensue.
A Full Regenerative Portfolio for Clinical Success
Juventix Regenerative Medical has a vast array of products, devices and services tailored for the regenerative professional. Our sister company, Integrative Practice Solutions, has a patented process for the treatment of osteoarthritis of the knee and shoulder with safe and effective hyaluronic acid products.
Advancing Osteoarthritis Treatment with Juventix and IPS
The regenerative marketplace is exploding with technological advancements being added daily for both men and women. An increasing aging population is making osteoarthritis more and more prevalent. Integrative Practice Solutions and Juventix Regenerative Medical offers effective answers for these and many problems facing clinicians today. With our premier line of products, protocols, devices, services and experienced staff, our companies will aid and guide any professional in using the proper treatment protocol to provide excellent outcomes and increase patient satisfaction.
RESTORE, REVIVE, REGENERATE- JUVENTIX REGENERATIVE MEDICAL
Regenerative Regards,
Dr. Robert McGrath
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