Purpose: Preventing scar contracture is a goal. The report investigates the mechanism of dynamic actin-myosin filament-sliding pathway (AMFSP) on fibroblast driven extracellular matrix (ECM) reorganization in collagen lattices and rat wound repair. The apparent blockade of the AMFSP pathway hinders wound contraction. Methods: Human foreskin fibroblasts were assayed for fibroblast populated collagen lattice (FPCL) contraction after exposure to different inhibitors of the AMFSP: (1) ML-9 (20mM), (2) ML-7 (10mM), (3) W7 (5mM), and (4) Fluphenazine (10mM). FPCL contraction was measured daily for 1 week and cells viewed under phase contrast microscopy. A 15 X 15 mm full thickness excisional wound was made on the right flank and the left flank of adult male rats. The left wounds were topically treated with W7 (2% in 50% DMSO) or Fluphenazine (300mM in H2O) and the right wounds with DMSO or H2O vehicle alone. On day 10, rat wound areas were measured and tissues prepared for histology. Wounds were stained with Hematoxylin and Eosin (H&E) and Sirius Red. Students paired t test was used for statistical analysis (*p < 0.01 considered significant). Results: ML-9 and ML-7, drugs that hinder myosin light chain kinase (MLCK) activity, and W7 and Fluphenazine, drugs that restrict calmodulin activation of MLCK, inhibited FPCL contraction (*p < 0.01). Fibroblast morphology was not altered by drug treatments. W7 and Fluphenazine inhibited rat wound contraction (*p < 0.01). Granulation tissue organization was altered in treated wounds. Conclusion: It is assumed that scar contracture is mediated by a similar mechanism as wound contraction; therefore, intervention in the AMFSP may be used to impact a number of human diseases. Drugs such as Fluphenazine hamper wound contraction significantly. Fluphenazine is an FDA approved agent that may be applied topically to prevent scar contracture in patients.
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