Wound-healing defects in mice lacking fibrinogen

In addition to its key role in the control of blood loss following injury, fibrin(ogen) has been proposed to play an important role in tissue repair b y providing an initial matrix that can stabilize wound fields and support l ocal cell proliferation and migration. To test directly these concepts, the effect of fibrinogen deficiency on cutaneous tissue repair in mice was inv estigated using incisional and excisional wounds. The time required to over tly heal wounds was similar in fibrinogen-deficient and control mice, but h istologic evaluation revealed distinct differences in the repair process, i ncluding an altered pattern of epithelial cell migration and increased epit helial hyperplasia. Furthermore, granulation tissue in fibrinogen-deficient mice failed to adequately close the wound gap, resulting in persistent ope n wounds or partially covered sinus tracts. The tensile strength of these w ounds was also reduced compared with control mice. The most profound defect in wound tissue organization was observed in fibrinogen-deficient mice fol lowing the subcutaneous implantation of a porous tubing chamber. Cells migr ated into the wall of the implants at a similar rate as control mice, but c ells from fibrinogen-deficient animals were unable to efficiently organize and migrate into wound fluid-filled dead space within the center of the imp lants. These studies show that re-epithelialization, granulation tissue for mation, including the establishment of neovasculature, and the formation of fibrotic scar tissue can proceed in the absence of fibrin(ogen) and all of its proteolytic derivatives. However, fibrin (ogen) is important for appro priate cellular migration and organization within wound fields and in initi ally establishing wound strength and stability. (C) 2001 by The American So ciety of Hematology.