Glycated Chitosan Derivatives Inhibit Myofibroblast Form and Function in Vitro

Abstract

Fibrotic diseases like Dupuytren's contracture (DC) involve excess scar tissue formation. The differentiation of fibroblasts into myofibroblasts plays a main role in DC as it generates contraction in areas without wound openings, leads to the deposition of scar tissue, and eventually flexes one or more fingers. Additionally DC has a high recurrence rate. Previously we showed glycated chitosan (GC), an immunoadjuvant polysaccharide, inhibited myofibroblast differentiation in a DC fibroblast culture; our goal was to expand those results to include other DC cell lines and determine whether single-walled carbon nanotube-conjugated GC (SWNT-GC) would be similarly effective. The GC-incorporated and vehicle control (water) stress-relaxed collagen matrices, in vitro 3D models, were used to show the compaction (anchored matrix height reduction) of DC fibroblasts using optical coherence tomography for 12 days. Fibroblasts were unable to compact in GC- and SWNT-GC-collagen matrices to the same extent as vehicle control lattices. Proliferative myofibroblasts were identified by the presence of alpha smooth muscle actin via immunofluorescent staining. Compared to control conditions there were fewer myofibroblasts in GC and SWNT-GC treatments but without a significant decrease in the number of nonproliferative fibroblasts. This suggests GC and SWNT-GC may be a possible treatment for the recurrent problem of fibrotic diseases by inhibiting fibroblast compaction and myofibroblast phenotypes.