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THE NATURAL ROLE OF HYALURONAN IN WOUND HEALING

With a tissue injury, individual components of extracellular matrix are damaged not only mechanically, but also, and in particular, by bacteria or by the body's own immune cells. Injury results in hyaluronan fragmentation in hyaluronan with very low molecular weight. These small fragments activate the immune cells and thus support the first phase of the wound healing process – inflammation. At the same time they activate cells responsible for the regenerative phase of the wound healing process. Hyaluronan is one of the first components synthetized at the point of injury. Its subsequent role is to create a proper moist environment in the wound, to support the synthesis of other parts of connective tissue and cell reproduction, and to ensure the proper arrangement of the extracellular matrix.

Hyaluronan plays different roles in the body depending on its molecular weight. High molecular weight hyaluronan can be seen as an organizer of the extracellular matrix, while hyaluronan with molecular weight below 200kDA works as an informative molecule.

function of external hyaluronan in wound healing process

 

Hyaluronan with a high molecular weight (millions of Da) forms a net-like structure in the extracellular area; this ability enables it to interact with proteoglycans, proteins and cell receptors. Hyaluronan organizes the extracellular matrix structure and integrates individual cells into the matrix. High molecular weight hyaluronan is expected to be responsible for the correct organization and orientation of collagen fibres and microfibrils. Due to hyaluronan's ability to interact with a cell´s receptors (CD44, RHAMM) hyaluronan can place cells into the extracellular matrix and at the same time it participates in cell migration, as cells migrate along hyaluronan fibres. Hyaluronan is an anionic polysaccharide with a high affinity to water. Together with proteoglycans (which also contain anionic polysaccharides), hyaluronan is responsible for extracellular matrix hydration, which facilitates the free penetration of nutrients and oxygen and does not prevent signal cells from diffusion in the tissue.

The ability of hyaluronan to eliminate scar formation during the wound healing process is explained on the basis of similarity with embryo tissue, which is rich in hyaluronan. Embryo tissue damage heals regeneratively without scar formation. Nevertheless, this idea is not in accordance with modern wound healing theory. It is more likely that hyaluronan attracting the "healing cocktail" at the same time reduces the content of the TGF factor in the "cocktail". (TGF is one of the factors responsible for scar formation.)

 

 

References:

David-Raoudi, M. et al.: Differential effects of hyaluronan and its fragments on fibroblasts: Relation to wound healing, Wound Rep Reg, 2008, 16, 274–287
 
Sterna, R. et al.: Hyaluronan fragments: An information-rich system, Europ J Cell Biol, 2006, 85, 699–715
 
Wilgus, T.A.: Regenerative Healing in Fetal Skin: The Review of the Literature, OWM, 2007, 53, 16-31
 
Yannas, I.V. et al.: Early Fetal Healing as a Model for Adult Organ Regeneration, Tiss Eng 2007, 13, 1789-1798