LAUSR

Extracellular matrix (ECM) play a double-edged sword role for controlling the differentiation of fibroblast toward contractile myofibroblast in the wound healing process. However, the exact structure-function relationship between ECM morphology and fibroblast behaviors still remains unclear. To better understand this relationship, herein we designed and prepared a series of biocompatible polycaprolactone (PCL)-based fibers with different fiber diameters (nano vs. micro) and different alignments (random vs. aligned) using a simple electrospinning, with a particular attention to the morphological effect of PCL fiber scaffolds on guiding fibroblast behaviors. Microfibers with the larger fiber diameters induce less cell spreading, adhesion, differentiation, and migration due to its lower surface tension. In contrast, nanofibers will retain fibroblast cells with typical spindle-shapes and promote the expression of focal adhesive proteins through the integrin pathway. Furthermore, nanofibers up-regulate the expression α-smooth muscle actin (α-SMA), transforming growth factor (TGF-β), and vimentin filaments, confirming that the size change of PCL fiber matrix from micrometers to nanometers indeed alter fibroblast differentiation to activate more α-SMA-expressed contractile myofibroblast. Such fiber size-dependent fibroblast behavior is largely attributed to the enhanced surface tension from the dressing matrix, which helps to promote the conversion of fibroblasts to myofibroblasts via either tissue regeneration or fibrosis. Therefore, this work further indicated the reason of re-arrangement of collagen from nano tropocollagen to micro collagen bundles during the wound healing process can reverses fibroblasts to myofibroblasts from motivated to demise. This finding allows us to achieve the structural-based design of new fibrous matrix for promoting wound healing and tissue regeneration.