The primary function of a fibrin clot in a wound is hemostasis.
As a secondary function, the clot provides a provisional extracellular
matrix (ECM) for cell recruitment to the wound site. It has recently
become clear, however, that fibrin, when formed from fibrinogen
that is commercially available or prepared by published protocols,
does not support this secondary ftinction. Therefore, the global
AIM of this proposal is to develop a hemostatically functional fibrin
matrix that facilitates cell recruitment to a site of injury. Such
a product would be useful in clinical settings where both optimal
hemostasis and a rapid formation of new tissue are needed such as
freshly debrided chronic cutaneous ulcers and fresh surgical and
traumatic wounds that cannot be closed. To this end we have recently
discovered a fibrinogen preparation that supports cell recruitment.
However' the critical components of this preparation, other than
fibrinogen and fibronectin, have not been characterized. Therefore,
we will use a recently designed in vitro assay for cell migration
across three-dimensional ECM boundaries to further define and characterize
the essential components of a novel fibrinogen preparation that
when clotted as a matrix composite elicits optimal fibroblast migration
(AIM 1) and to determine whether addition of various components,
that are found in the active fibrinogen isolates, to highly purified
fibrinogen (Peak 1) will reconstitute the activity (AIM 2). In future
work we will determine whether fibrin matrix composites that are
optimal in vitro for cell migration are also optimal in vivo for
cutaneous wound healing.
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