Excessive
scar formation caused by cutaneous injury leads to
pruritus,
pain,
contracture,
dyskinesia, and unpleasant appearance. Functional
wound dressings are designed to accelerate wound healing and reduce
scar formation. In this study, we fabricated aligned or random
polycaprolactone/
silk fibroin electrospun nanofiber membranes with or without
lovastatin loading, and then evaluated their
scar-inhibitory effects on
wounds under a specific tension direction. The nanofiber membranes exhibited good controlled-release performance, mechanical properties, hydrophilicity, and biocompatibility. Furthermore, nanofibers' perpendicular placement to the tension direction of the
wound most effectively reduced
scar formation (the
scar area decreased by 66.9%) and promoted skin regeneration in vivo. The mechanism was associated with aligned nanofibers regulated
collagen organization in the early stage of wound healing. Moreover,
lovastatin-loaded nanofibers inhibited myofibroblast differentiation and migration. Both tension direction-perpendicular topographical cues and
lovastatin synergistically inhibited mechanical transduction and
fibrosis progression, further reducing
scar formation. In summary, our study may provide an effective
scar prevention strategy in which individualized dressings can be designed according to the local mechanical force direction of patients'
wounds, and the addition of
lovastatin can further inhibit
scar formation. STATEMENT OF SIGNIFICANCE: In vivo, cells and
collagen are always arranged parallel to the tension direction. However, the aligned topographic cues themselves promote myofibroblast differentiation and exacerbate
scar formation. Electrospun nanofibers' perpendicular placement to the tension direction of the
wound most effectively reduces
scar formation and promotes skin regeneration in vivo. The mechanism is associated with tension direction-perpendicular nanofibers reregulate
collagen organization in the early stage of wound healing. In addition, tension direction-perpendicular topographical cue and
lovastatin could inhibit mechanical transduction and
fibrosis progression synergistically, further reducing
scar formation. This study proves that combining topographical cues of
wound dressing and drugs would be a promising
therapy for clinical
scar management.