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Hyaluronic Acid  

OVERVIEW
History and Significance
Applications

CHEMISTRY
General Manufacturing Process
Available Formulations
Biologic Activity
Hydration and Re-epithelialization
Regeneration

APPROVED INDICATIONS AND THERAPEUTIC USE
Dermal Filler
Dermal Hydration
Rejuvenation

CLINICAL CONSIDERATIONS
Patient Instructions
Duration and Frequency of Treatment
Contraindications, Warnings, Precautions

PRODUCT SELECTION FOR RESULTS

REFERENCES

Hyaluronic Acid  

 OVERVIEW

Hyaluronic acid is a naturally occurring polymer synthesized by the body and found primarily in connective tissue. It serves to lubricate and cushion body tissue, such as in the joints and eyes. Nutrition, hormone levels, and infection may affect hyaluronic acid production. Abnormal levels of hyaluronic acid can contribute to joint degeneration, heart conditions, glaucoma, and other connective tissue conditions. The effects of hyaluronic acid supplements through injections and topical applications promote the synthesis of biologic scaffolding and repair. It is currently used in dermatology for collagen support.

 History and Significance

Hyaluronic acid, also known as hyaluronan or hyaluronate, is found in connective, epithelial, and nerve tissues. It is a primary component of the extracelluar matrix and plays a role in cell proliferation and migration. Hyaluronan forms hydroscopic monomer aggregates which in turn effect resilience, elasticity, and viscosity in cartilage, collagen, and sinovial fluid. The body naturally produces hyaluronic acid and its synthesis declines with age, contributing to degeneration in joints, eye sight, and skin.

 Applications

Hyaluronic acid is biocompatible and valuable as a biologic scaffold. Hyaluronan products have been approved for use in ophthalmic surgery, orthopedic surgery, and dermatology. In 2003, the FDA approved the first injectable dermal filler comprised of hyaluronic acid. Hyaluronic acid is hydroscopic and can be cross-linked to other compounds to induce migration into the cell. Treatment containing hyaluronic acid is ideally suited for therapeutic and cosmetic applications because of its critical role in biologic processes and it biocompatibility through the dermis.

 CHEMISTRY

Chemical name: Hyaluronic acid (also known as hyaluronan or hyaluronate)


Hyaluronic acid is a polymer of disaccharides containing D-glucuronic acid and D-N-acetylglucosamine and is synthesized to a white crystalline powder for biologic use.1

 General Manufacturing Process

Hyaluronic acid can be extracted from animal sources such as rooster combs. Currently, non-animal sourced hyaluronic acid is commercially synthesized through bacterial fermentation of sugars to a high degree of purity. Non-animal sourced hyaluronic acid ensures low reaction and eliminates cross-contamination or transmission of endotoxins.1

 Available Formulations

Hyaluronic acid is available in cream and gel formulations for dermatologic use. The hydrating and regenerative properties of hyaluronic acid are often combined with other treatments to correct the effects of tissue degeneration and to impart structural support and tissue hydration.

 Biologic Activity

Hyaluronic acid is abundant in body tissues and it is produced primarily in connective tissue. It is abundant in the extracellular matrix and is synthesized by a class of integral membrane proteins (hyaluronan synthases, HAS). It is involved in the wound-healing process by its function in cellular migration: hyaluronic acid promotes inflammation by enhancing cellular infiltration and it moderates the inflammatory response through the granulation tissue matrix. As such, hyaluronic acid is critical in cellular regeneration and tissue hydration.

 Hydration and Re-epithelialization

Hyaluronic acid has been shown to enhance cellular infiltration through its presence in the extracellular membrane. It is produced by endothelial cells in response to inflammatory cytokines such as TNF-alpha and it binds to CD44 which mediates cell aggregation, migration, proliferation, and activation. Low molecular weight hyaluronic acid has been shown to improve the release of beta-defensins by keratinocytes, promoting epithelial defense against infection.3 The presence of hyaluronic acid in epithelial tissue has also been shown to promote keratinocyte proliferation and increase the presence of retinoic acid (vitamin A), further promoting skin hydration.

 Regeneration

Hyaluronic acid and its interaction with CD44 drive the maintenance and establishment of collagen synthesis and normal skin function. Hyaluronic acid is present in the extracellular matrix of basal keratinocytes and the structural integrity of the dermal collagen matrix through stimulation of collagen fragments and fibroblast penetration3. Decreased levels of hyaluronic acid correlate to decreased levels of skin elasticity, impaired local inflammatory response, and reduced tissue repair due to degeneration of the granular tissue matrix.2,3

 APPROVED INDICATIONS AND THERAPEUTIC USE

APPROVED INDICATIONS
Dermal Filler
Dermal Hydration
Rejuvenation
Hyaluronic acid is approved for select surgical procedures and for dermatologic use as dermal fillers to harness its regenerative and hydroscopic effects. Since hyaluronan is naturally produced by the body, it can be safely absorbed with long-term application.

 Dermal Filler

In 2003, hyaluronic acid gel was approved for mid to deep implantation as a dermal filler to fill moderate to severe facial wrinkles and folds (e.g., nasolabial folds). Cosmetic surgeons and dermatologists inject hyaluronic acid in gel particles to add volume or bulk, primarily in the face. Treatment is performed in a nonsurgical setting and effects subside over time, as the hyaluronic acid is absorbed by the body.4

 Dermal Hydration

As a glycosaminoglycan, hyaluronan sequesters water into the cell through the formation of aggregates. Hyaluronic acid promotes keratinocyte proliferation and binds with CD44 to maintain and repair the collagen matrix within a hydrated scaffold. Hyaluronan is a major component of sinovial fluid, and its concentration is directly associated with level of viscosity. Topical application of hyaluronic acid has been shown to significantly enhance dermal hydration through the attraction and retention of water molecules within the cellular matrix.

 Rejuvenation

Hyaluronic acid is applied topically to support collagen synthesis and to aid in normal keratinocyte functioning. Clinical studies have shown a decrease in hyaluronan in photodamaged skin, supporting its role in skin regeneration and homeostasis, its correlation with retinoic acid for tissue hydration,5 and its role in keratinocytes for epithelial defense.3 Hyaluronic acid has been used as an adjunct to dermatologic treatments for its unique role as a counteracting agent in the inflammatory process,6 and formulations containing hyaluronic acid can optimize adjunctive moisturizing and penetration effects.

 CLINICAL CONSIDERATIONS

Hyaluronic acid is included in the KAVI Anti-Aging product line to promote cellular repair and enhance skin hydration. Hyaluronic acid is effective with other moisturizers for maintenance and is effectively combined with glycolic acid and with retinol to optimize rejuvenation benefits: rehydration, collagen repair, and skin hydration.

 Patient Instructions; Duration and Frequency of Treatment

Glycolic and Hyaluronic Serums: Apply a thin layer on the skin after cleansing to repair and hydrate delicate tissue.
Frequency: Application twice per day is recommended.
Advanced Melanin Repair Serum: Apply a thin layer on the target area twice per day after cleansing to correct pigmentation variance.
Frequency: Application twice per day is recommended.
Keratolytic Enzyme Mask (safe for sensitive skin): Apply a thin layer on the target area and leave on as directed (below). Remove by rinsing with cool water or wipe with damp cloth.
First use: leave on for up to 5 minutes.
Subsequent uses: leave on for 10-15 minutes.
Frequency: Up to two times per week is recommended.

 Contraindications, Warnings, Precautions

For external use only. Seek medical attention if dryness / dermal dehydration persists. For products containing glycolic acid, salicylic acid or retinol, reduce frequency of use if excessive irritation ensues and wear appropriate sunblock as recommended.

 PRODUCT SELECTION FOR RESULTS

Hyaluronic acid is a safe and effective option to enhance any dermatologic treatment plan. The KAVI Anti-Aging product line includes the benefits of hyaluronic acid to promote continued results during maintenance cycles, and all hyaluronic acid products are formulated to complement other KAVI treatment regimens.

Additional information on the KAVI 95% Hyaluronic Acid Serum
Additional information on the KAVI 15% Glycolic Acid, 45% Hyaluronic Acid Serum
Additional information on the KAVI 30% Glycolic Acid, 45% Hyaluronic Acid Serum
Additional information on the KAVI 1% Alpha Arbutin, 8% Glycolic Acid, 50% Hyaluronic Acid Serum
Additional information on the KAVI Pumpkin, Pineapple, and Papaya Enzyme Mask with 5% Hyaluronic Acid

 REFERENCES

1. Longin F. "Hyaluronic Acid - The Biotech Way", Available online. Accessed June 2, 2009.
2. Gariboldi S, Palazzo M, Zanobbio L, et al. "Low Molecular Weight Hyaluronic Acid Increases the Self-Defense of Skin Epithelium by Induction of Beta-Defensin 2 via TLR2 and TLR4", J Immunol. Aug, 2008; 181(3):2103-10.
3. Fisher GJ, Varani J, Voorhees JJ. "Looking Older: Fibroblast Collapse and Therapeutic Implications", Arch Dermatol. May, 2008; 144(5):666-72.
4. Carruthers J, Cohen SR, Joseph JH, Narins RS, Rubin M. "The Science and Art of Dermal Fillers for Soft-Tissue Augmentation", J Drugs Dermatol. Apr, 2009; 8(4):335-50. Review.
5. Bauer SM, Bauer C. "The Use of Sodium Hyaluronate for the Treatment of Radiation Recall Dermatitis", J Oncol Pharm Pract. Jun, 2009; 15(2):123-6.
6. Dudelzak J, Hussain M, Phelps RG, et al. "Evaluation of Histologic and Electron Microscopic Changes After Novel Treatment Using Combined Microdermabrasion and Ultrasound-Induced Phonophoresis of Human Skin", J Cosmet Laser Ther. Dec, 2008; 10(4):187-92.

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