Oriented Protein Nanofibers via Unfolding-Based Electrospinning for Reduced Scar Formation: Balancing Contraction and Regeneration

Abstract

Excessive wound contraction is an important driver of pathological scar formation, causing functional impairment, limited mobility, and significant psychological distress for millions of patients worldwide. Therefore, developing wound dressings that can inhibit excessive contraction while still supporting efficient wound repair is of critical clinical importance. In this work, a protein unfolding-stabilization strategy was employed to convert the globular protein bovine serum albumin (BSA) into random and oriented BSA fiber membranes (RBFM and OBFM) via electrospinning, establishing a new pure protein-based wound dressing material with intrinsic biodegradability and biocompatibility. We found that the high orientation of wound dressing plays a vital role in promoting scarless wound healing. The OBFM facilitates the attachment and guided alignment of skin cells while suppressing α-SMA expression, thereby inhibiting myofibroblast differentiation and excessive cytoskeletal contractility. As a result, the OBFM effectively moderates wound contraction in the early stage (∼48% reduction in wound contraction at day 3 compared with the no-treatment and RBFM groups), which is critical for preventing pathological scar formation, while simultaneously accelerating wound closure in the later stage (∼69% reduction in wound area at day 7 compared with the no-treatment and RBFM groups). These findings demonstrate that an oriented protein-based dressing can simultaneously inhibit excessive contraction and promote wound closure, representing an important step toward scar-reducing wound repair.