Chitosan inhibits gap junction formation and contraction of an in vitro wound model

摘要

Wound healing is a process tightly regulated by interactions between cells, cytokines and the extra-cellular matrix. Wound contraction is an important stage in the healing response, mediated by mechanical forces exerted in the matrix by myo-fibroblasts. Chitosan, a polymer of n-acetyl glucosamine, was examined for its wound contraction inhibition effects. Three dimensional collagen gels populated with human dermal fibroblasts (HDFs) were used as wound contraction models. Contraction was measured by surface planimetry. Collagen control gels contracted 87.8/spl plusmn/2.7% (mean/spl plusmn/SD) of their initial surface area whereas collagen-chitosan (3:1) blends contracted only 36.8/spl plusmn/11%. Since wound contraction is mediated by myo-fibroblast transformation, the effect of chitosan on myo-fibroblast transformation was studied. Such transformations are characterized by the formation of gap junctions in fibroblasts. Gap junction formation was measured by a dye transfer assay. The efficiency of gap junction formation was less in fibroblasts plated on collagen-chitosan surfaces (18.7/spl plusmn/5%) when compared to collagen control surfaces (79.1/spl plusmn/8.4%). These data support the hypothesis that chitosan inhibits contraction of a wound model due to the inhibition of gap junction formation and hence the transformation of resting fibroblasts into myo-fibroblasts.