Tissue engineering approach using fibrous scaffold with matricellular protein for wound healing
Date of Issue2018-02-09
Interdisciplinary Graduate School (IGS)
Electrospun fibrous scaffolds, which closely mimic native extracellular matrix (ECM) fibrous hierarchical physical structures, are promising candidates as grafts for regenerative medicine. For wound healing applications, the interactions between scaffold topographic features and cellular responses, especially the directional cell migration and phenotypic change, are critical but not well explored yet. In this regards, this dissertation aims to design superior fibrous structure for tissue-engineered skin graft and reveal the possible underlying mechanisms. Accelerated and persistent migration of human dermal fibroblasts (HDFs) was observed on fibers with aligned orientation, which might be attributed to confinement expression of focal adhesions and upregulation of Cdc42 GTPase activity. Additionally, it was found that aligned fibers were capable to induce myofibroblast differentiation of HDFs. However, it was remarkably noted that the introduction of matricellular protein Angiopoietin-like 4 (ANGPTL4) was able to reverse the phenotypic alteration induced by aligned fibers. Higher transforming growth factor-β1 (TGFβ1) level in HDFs cultured on aligned fibers might result from mechanical activation, which implied the possible underlying mechanism of aligned fiber-induced myofibroblast differentiation. These discoveries indicated that tissue-engineered fibrous grafts with precise fiber alignment modulation and ANGPTL4 releasing properties may thus be promising scaffolds to promote wound repair while minimizing scar formation for efficacious wound therapies in the future.