Our technology.

Arthromac® products are made with a hyaluronic acid produced in France, with the highest level of purity available in the industry today, and cross-linked through a proprietary process using no chemical agent called X-Click Technology.

Hyaluronic acid

About

Hyaluronic acid (HA), a linear polysaccharide that occurs naturally in the synovial fluid and cartilage, is fully biocompatible and has remarkable properties for the treatment of osteoarthritis.

However, once injected into the tissues, a natural and unmodified molecule of HA will be rapidly degraded and absorbed.

​This depolymerization which transforms long HA chains (polysaccharides) into smaller HA units (oligosaccharides) is due to enzymes (hyaluronidases), free radicals, heat and mechanical stresses. Therefore, to increase the residence time of HA and its beneficial action in the tissues, it is crucial to protect it against these enzymatic, oxidative, thermal and mechanical degradations by a process of cross-linking (reticulation).

Chemical Cross-linking

To improve the duration of HA in vivo, a common method is to form a hydrogel by covalently cross-linking the HA polymer chains into a three-dimensional network. Unfortunately, this cross-linking process involving chemical agents (such as such as 1,4-butanediol diglycidyl ether (BDDE), formaldehyde, divinyl sulfone etc.) impairs the biocompatibility, the ease of injectablity, as well as the natural viscoelastic and biological properties of the HA molecule. The later will have an impaired biocompatibility with a greater risk of hypersensitivity reactions [1-5], a more rigid structure, a lower water-binding capacity, and a lower capacity on the production of extracellular matrix components [6].


Such adverse events and disadvantages are avoided with the use of a physical cross-linking instead of a chemical one [1, 7, 8].

Physical cross-linking

NOVATEX BIOENGINEERING, an Astagen Therapeutics division, through its collaboration with the CNRS (The French National Centre for Scientific Research), has developed a new cross-linking technology, called X-Click technology, making it possible to physically transform a linear HA into a stabilized three-dimensional HA network without any chemical agents.


This proprietary technology is based on the click chemistry [9] and used crystallization to create intermolecular and intramolecular hydrogen bonding (Fig 1).

This physical hydrogel is a good alternative because of the absence of organic solvents and toxic cross-linking agents [10-14].


As a result, the HA cross-linked with X-Click Technology is non-toxic, fully biocomptabible, easy to inject, with unaltered viscoelastic and biological properties [15,16].

Classical method:
Chemical cross-linking with BDDE

  • LOSS OF THE NATURAL VISCOELASTIC AND BIOLOGICAL PROPERTIES OF THE HA

    Rigid structure

    Low stimulation of collagen and HA synthesis

  • RISK OF HYPERSENSITIVITY REACTIONS

X-Click Technology
Physical cross-linking without chemical agent

  • PRESERVATION OF THE NATURAL VISCOELASTIC AND BIOLOGICAL PROPERTIES OF THE HA

    Dynamic structure

    High stimulation of collagen and HA synthesis

  • NO RISK OF HYPERSENSITIVITY REACTIONS

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