Hyaluronic acid and cross-linked Hyaluronic Acid

Modifcations of Hyaluronic Acid (HA)

HA can be modified and formulated into almost any form:

• Nanocarriers

• Micelles

• Cross-linked HA molecules

• Stabilized tissue fillers

• Hydrogels

• Powders/mini-pellets

• Implants

• Sponges

Crosslink of Hyaluronic Acid

Aims of crosslinkage:

• "stabilization" to improve resistance to enzymatic degradation longer duration in the skin more resistant to degradation

• more complex chemical structure

• more robust physical barrier to the emzymatic and free radical breakdown in the phagocytes (Fredrickson 2008′)

• The resulting hyaluronan derivatives have physicochemical properties that differ from the native polymer, but depending on the crosslinkage the derivatives can retain the biocompatibility and biodegradability.

Crosslinkage of Hyaluronic acid

• Worldwide only two substances for crosslinkage are used: DVS and BDDE

• Both substances are as a single molecule toxic but loose their harmful character through binding onto the Hyaluronic acid molecule

Crosslinked "stabilized" hyaluronic acid:

Chemical modification of the molecule:

• crosslinking has to take place at the OH-groupsto secure the enzymatical degradation

• carboxylate- und acetamido groups stay stabil polyanionic character unmodified

  - the biological properties of linear hyaluronic acid are unchanged

  - high biocompatibility, no allergic reaction

Cave: Granuloma = immun response!