Formation and Remodeling of the Early Wound Matrix.

We have proposed that an early event in wound healing involves the synthesis of hyaluronic acid (HA) by blood cells in the clot and that HA specifically interacts with fibrin to create a second matrix within the wound. Peripheral cells then migrate into the wound and begin to remodel the matrix. To test this model we have synthesized a unique derivative of HA, hyaluronate-amine, which has been used to prepare (1) radioiodinated HA to study cell surface receptors, (2) synthetic culture surfaces to study cell interactions with immobilized HA and (3) HA-sepharose, an affinity chromatography media. We have also used the HA-sepharose to show, as predicted by our proposed model, that fibrinogen specifically binds to HA. This is the first demonstration of such an interaction and would be of major significance in understanding the important early events necessary for prompt and efficient wound healing.