In healing and scarring the contractile process plays a significant role. In burn patients, scar contracture is a major contributor to morbidity. Mesenchymal cells usually fibroblasts produce the contractile force. A better understanding is needed of the morphological dynamics of forces generated by these cells for the eventual modulation of scar contracture. A 3 dimensional model composed of cultured fibroblasts suspended in a collagen matrix with serum containing culture medium is one method utilized to evaluate the contractile process. This fibroblast populated collagen lattice, FPCL, undergoes a reduction in size referred to as lattice contraction. Two other more simple in vitro models of the contractile process are the Cell Contraction model where the functioning of the cytoskeletal microfilament apparatus can be manipulated and the Thin-film Wrinkling model where the cytoplasmic components of cell movement can be followed under dynamic conditions. A number of purified cytoskeletal proteins, (actin, alpha-actinin and vinculin) are labeled with fluorescent tag and microinjected into cells prior to there introduction into one of our in vitro models. The location of these tagged proteins in fibroblasts may point to specific importance each has in the contractile process. In addition, the finding that type III collagen FPCL contract more than FPCL made with type I collagen suggest that the collagen matrix of scar may control the contractile process. The importance of some inflammatory cell products such as IL-1 from macrophages and lymphokines isolated from lymphocytes grown out from hypertrophic scars will be studied in terms of influencing collagen synthesis and the contractile process. Another approach to constrain this process is to limit connective tissue deposition. A combination of cortisone and oral heparin will be tried to modify neovascularization. Reducing neovascularization of wounds should reduce the amount of new connective tissue deposited which should affect the contractile process.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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Massachusetts General Hospital
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Choi, M; Ehrlich, H P (1993) U75412E, a lazaroid, prevents progressive burn ischemia in a rat burn model. Am J Pathol 142:519-28
Rittenberg, T; Ehrlich, H P (1992) Free fatty acids and dialyzed serum alterations of fibroblast populated collagen lattice contraction. Tissue Cell 24:243-51
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Rockwell, W B; Ehrlich, H P (1991) An ibuprofen-antagonized plasmin inhibitor released by human endothelial cells. Exp Mol Pathol 54:1-9
Rittenberg, T; Burd, D A; Ehrlich, H P (1990) Soluble factor(s) in rat wound fluid inhibit fibroblast populated lattice contraction. Exp Mol Pathol 52:132-40
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