Hyaluronic acid

Author: Prof. Dr. med. Peter Altmeyer

Co-Autor: Hadrian Tran

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Last updated on: 22.05.2022

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Synonym(s)

CAS number 9004-61-9; Hyaluronan; hyaluronic acid (engl.)

Definition
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Hyaluronic acid is an important mucopolysaccharide (glycosaminoglycan) in which glucuronic acid is glycosidically linked to N-acetylglucosamine. This in turn is linked to the next glucuronic acid in the polymeric chain. A chain typically consists of 250 to 50,000 disaccharide units. Hyaluronic acid is a viscous substance with an enormous water-binding capacity. 1g hyaluronic acid can bind about 6L of water. Hyaluronic acid is a component of the extracellular matrix (ECM) of vertebrates.
Hyaluronic acid is obtained partly from animal source material (e.g. cockscomb) or biotechnologically. In the case of hyaluronic acid products obtained from cockscombs, allergic reactions can occur if there is a sensitization to bird proteins (contamination of the preparations).
Hyaluronic acid is present in many tissues, including the connective tissue of the skin as a long-chain polysaccharide and gives the tissue plastic firmness. For example, the vitreous body of the human eye consists of 98% water bound to 2% hyaluronic acid. Furthermore, hyaluronic acid is the main component of the joint synovia.
Furthermore, hyaluronic acid is involved in the formation of even larger proteoglycans (e.g. in hyaline cartilage).
The hyaluronic acid is assembled by integral membrane enzymes (hyaluronic acid synthases). Vertebrates possess 3 different HA synthases (HAS1 - HAS3). These enzymes constantly transfer new monosaccharide building blocks into the growing chain. The monosaccharide is finally removed from the cell by an ABC transporter and reaches the interstitium.
Hyaluronic acid applications are widely used in medicine.

Field of application/use
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Medical and cosmetic indications:
Hyaluronic acid for acute and chronic wounds:The

use of hyaluronic acid in hydrogels for wound care is propagated. Reliable results are to be awaited.

Hyaluronic acid for dry mucous membranesSome
nasal sprays contain hyaluronic acid to counteract the drying of the nasal mucous membranes. Hyaluronic acid can also be used in eye drops for the treatment of sicca symptoms (dry eye).

Intra-articular applications of hyaluronic acid in osteoarthritisThe
data situation regarding its actual efficiency is regarded as doubtful by experts.

Use of hyaluronic acid as an injectable filler material in aesthetic medicineThe
use of hyaluronic acid in aesthetic medicine is a long-established procedure. Hyaluronic acid preparations are by far the most frequently used materials used as injectable filling materials (fillers) for wrinkle injections. Furthermore, hyaluronic acid fillers are used to model the lips (enlargement, "injecting") or to build up facial contours. The effect of hyaluronic acid-based fillers is maintained for 6-9 months. The treatment can be repeated as often as desired. Preparations based on non-animal, stabilized hyaluronic acid (NASHA) are becoming increasingly common. These preparations have been specially developed for the treatment of body deformities.
The use of hyaluronic acid is propagated in the treatment of atrophic scars (scars that have sunk below the skin level). It is unclear to what extent this procedure triggers a collagen production and thus causes a permanent effect.

Hyaluronic acid for topical application in cosmeticsHyaluronic acid preparations
are widely used in cosmetic products, among others also as orally (!) applicable preparations. As hyaluronic acid molecules are not absorbed by the skin due to their size, hyaluronic acid fragments (hydrolyzed sodium hyaluronate) are used for this purpose. This "low-molecular hyaluronic acid" is assumed to penetrate into the skin. There are some studies with positive results which need further confirmation.

Hyaluronic acid is also offered in tablet form as a dietary supplement.

Undesirable effects
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Side effects were injection-related infections (erysipelas, abscesses) as well as late onset (after 8-10 weeks) local granulomatous reactions, which occurred in 0.5% and 4.5% of treated subjects, depending on the study. Furthermore, activation of sarcoidosis has been described. Generalized exanthema may occur after intra-articular injections of hyaluronic acid.

Very rare side effects include allergic shock, bruising of the joint, severe acute inflammatory reactions, rhinitis, joint stiffness, tenosynovitis, bursitis, fever, and muscle pain.

In rare cases, partial or complete loss of vision occurs with injections in the upper part of the face, i.e. the nose, glabella or forehead; in 98% of those affected, this was a unilateral visual impairment. The symptoms usually appear directly after the treatment: severe pain in the eye region, restriction of vision, ptosis, ophthalmoplegia, exotropia, pupillary disturbances or unspecific complaints such as headache , also nausea. Embolic occlusions of the hyaluron filler with occlusion of retinal arteries are suspected.

Literature
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  2. Beniamino P et al (2016) Cross-linked hyaluronic acid in pressure ulcer prevention. J Wound Care 25:400-405.
  3. Bulam H et al. (205) A severe acute hypersensitivity reaction after a hyaluronic acid with lidocaine filler injection to the lip. Arch Plast Surg 42:245-247.
  4. Dalmedico MM et al. (2016) Hyaluronic acid covers in burn treatment: a systematic review. Rev Esc Enferm USP 50:522-528.
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  15. Walker L et al. (2018) "This month's guideline: Visual Loss Secondary to Cosmetic Filler Injection." The Journal of clinical and aesthetic dermatology 11.5: E53-E55.

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Last updated on: 22.05.2022