Hyaluronic Acid Knowledge

Demystifying non cross linked hyaluronic acid

What is non cross linked hyaluronic acid?

Non cross linked hyaluronic acid is a non-sulfated linear anionic polysaccharide. It is composed of β-D-glucuronic acid and N-acetyl β-D-glucosamine units alternating through β-1,4 and β-1,3 linked together by glycosidic bonds. They have been widely studied since they were discovered by the French scientist PORTES in 1880.

Applications of non cross linked hyaluronic acid

As the main component of the extracellular matrix, non-cross-linked hyaluronic acid has excellent biocompatibility, degradability, anti-inflammatory activity, and low immunogenicity, and can participate in cell differentiation, angiogenesis, inflammatory response, and wound healing.

It has great application prospects in the fields of biomedicine, drug delivery, tissue engineering, food and cosmetics, and other fields due to its characteristics in multiple biological processes.

  • In the aesthetic field, non cross linked hyaluronic acid is used to fill facial or eye-sunken areas due to its ability to reduce pigmentation and promote dermal thickening and scar remodeling with minimal adverse reactions.
  • In the medical field, non cross linked hyaluronic acid can be used for cystitis, vaginitis, and dry eye treatment due to its anti-inflammatory features, especially its contribution to arthritis treatment has significant clinical effects.
  • Meanwhile, the molecular weight range of non-cross-linked hyaluronic acid is wide.
    Usually, hyaluronic acid with a relative molecular weight lower than 10,000 is called hyaluronic acid oligosaccharide.

    Hyaluronic acid with a molecular weight between 10 000 and 250 000 is called low molecular weight hyaluronic acid.

    Hyaluronic acid with a molecular weight between 250 000 and 1 000 000 is called medium molecular weight hyaluronic acid.

    Hyaluronic acid with a molecular weight greater than 1,000,000 is called high molecular weight hyaluronic acid.

Current research has shown that non-cross-linked hyaluronic acid has a molecular mass dependence. Differences will affect its structure, rheological properties (zero shear viscosity, viscoelasticity, pseudoplasticity, etc.), and production properties such as biological activity, thus causing differences in clinical application.

The degradation mechanism of non cross linked hyaluronic acid

Non cross linked hyaluronic acid plays a vital role in the fields of cosmetics, biomedicine, and tissue engineering due to its excellent biocompatibility and biodegradability.

However, degradability also means that non cross linked hyaluronic acid is quickly cleared after entering the body.
Degradability also means that non-cross-linked hyaluronic acid will be quickly degraded and metabolized by hyaluronidase and other enzymes after entering the body, making it difficult to continue to effectively function, and hindering its wide clinical application.

The degradation mechanism of non cross linked hyaluronic acid in the body is related to the breakage and formation of glycosidic bonds. It mainly achieves in vivo degradation through two different mechanisms: specific enzymatic hydrolysis and non-specific free radical degradation. 

The enzymatic decomposition of non-cross-linked hyaluronic acid in the body is mainly completed by the hyaluronidase family. Hyaluronidase refers to a type of glycosidase that can degrade hyaluronic acid and some glycosaminoglycans into disaccharides or small molecule oligosaccharides.

Differences between cross linked hyaluroni acid and non cross linked hyaluronic acid

Compared with cross-linked hyaluronic acid, non-cross-linked hyaluronic acid has a short half-life and poor stability.

The product is susceptible to degradation due to external factors (such as temperature, storage conditions, pH value, ultrasound, ultraviolet light, and hydrogen peroxide) during storage and application, resulting in a decrease in molecular weight and at the same time changes in its structure, properties and biological activity, the effectiveness of hyaluronic acid is reduced.

However as a degradable biomaterial, non-cross-linked hyaluronic acid has high application potential in the fields of wound healing, tissue engineering, and aesthetic fields.

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