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Blood, 15 June 2001, Vol. 97, No. 12, pp. 3691-3698
PLENARY PAPER
Wound-healing defects in mice lacking fibrinogen
Angela F. Drew,
Hong Liu,
Jeffrey M. Davidson,
Cynthia C. Daugherty, and
Jay L. Degen
From the Division of Developmental Biology, Children's
Hospital Research Foundation, Cincinnati, OH; Department of Pathology,
Vanderbilt University Medical Center; and Department of Veterans
Affairs Medical Center, Nashville, TN.
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 by providing an initial matrix that can stabilize wound
fields and support local cell proliferation and migration. To test
directly these concepts, the effect of fibrinogen deficiency on
cutaneous tissue repair in mice was investigated using incisional and
excisional wounds. The time required to overtly heal wounds was similar
in fibrinogen-deficient and control mice, but histologic evaluation
revealed distinct differences in the repair process, including an
altered pattern of epithelial cell migration and increased epithelial
hyperplasia. Furthermore, granulation tissue in fibrinogen-deficient
mice failed to adequately close the wound gap, resulting in persistent
open wounds or partially covered sinus tracts. The tensile strength of
these wounds was also reduced compared with control mice. The most
profound defect in wound tissue organization was observed in
fibrinogen-deficient mice following the subcutaneous implantation of a
porous tubing chamber. Cells migrated into the wall of the implants at
a similar rate as control mice, but cells from fibrinogen-deficient
animals were unable to efficiently organize and migrate into wound
fluid-filled dead space within the center of the implants. These
studies show that re-epithelialization, granulation tissue
formation, 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 appropriate cellular migration and
organization within wound fields and in initially establishing wound
strength and stability.

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