An important aspect both of healing and scarring is the contractile process which is a major component of the morbidity associated with the discharged burn patient. Mesenchymal cells, referred to here as fibroblasts, produce the contractile forces generated in the contractile process. To better study and understand these mechanisms, and to gain possible control of these forces, a three dimensional in vitro model system, the fibroblast populated collagen lattice (EPCL) is employed. Tissue cultured fibroblasts suspended in a collagen matrix actively reduce the size of that matrix in the process known as lattice contraction. Local increases in prostaglandins (PGE) may be produced either by directly adding PGE or by stimulating the fibroblast endogenous synthesis of PGE2, which inhibit lattice contraction. Characteristics of lattice contraction inhibition are a morphological inability of the incorporated fibroblasts to spread and elongate, since they remain spherical in shape; and a biochemical increase in intracellular cAMP concentrations. It is proposed that cAMP inhibits lattice contraction by inhibiting the functions of intracellular microfilaments. In particular, microfilaments do not form """"""""stress fibers"""""""" resulting fibroblasts which cannot spread and elongate. Other cytoskeletal components such as microtubules and plasma membranes may also be altered. The dynamics of the structural changes of microfilaments, microtubules and plasma membranes will be monitored by the use of a non-immuno fluorescence probe, NBD-phallacidin, or by intracellular micro injections of fluorescently labeled microfilaments, microtubules or plasma membrane structural proteins prior to fibroblast incorporation into FPCL. Relationships will be searched for relating cytoskeletal and contractile apparatus elements and for the mechanisms of the contractile force developed by fibroblasts. It is anticipated that information from these in vitro studies will produce new approaches to the ultimate control of the contractile processes associated with in vivo healing and/or scarring.
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