Journal
ADVANCED HEALTHCARE MATERIALS
Volume 8, Issue 9, Pages -Publisher
WILEY
DOI: 10.1002/adhm.201801378
Keywords
ANGPTL4; electrospun fibrous scaffolds; fibroblast-to-myofibroblast differentiation; migration; wound healing
Funding
- Interdisciplinary Graduate School, Nanyang Technological University
- NTU/MOE Tier-1 [RGT 24/13]
- NTU-Norwestern Institute for Nanomedicine (NNIN)
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Electrospun fibrous matrices, mimicking extracellular matrix (ECM) hierarchical structures, are potential scaffolds for wound healing. To design functional scaffolds, it is important to explore the interactions between scaffold topographic features and cellular responses, especially directional migration and phenotypic changes, which are critical functional aspects during wound healing. Here, accelerated and persistent migration of human dermal fibroblasts (HDFs) is observed on fibers with aligned orientation. Furthermore, aligned fibers can induce fibroblast-to-myofibroblast differentiation of HDFs. During wound healing, the presence of myofibroblasts advances wound repair by rendering contractile force and ECM deposition within the early and middle courses, but its continuous persistence in the later event may not be desired due to the contribution in pathological scarring. To tune the balance, it is noted in this work that the introduction of matricellular protein angiopoietin-like 4 (ANGPTL4) is capable of reversing the phenotypic alteration induced by aligned fibers, in a time-dependent manner. These results indicate fibrous matrices with oriented configuration are functional in mediating directional cell migration and phenotypic change. The discoveries further suggest that tissue-engineered fibrous grafts with precise alignment modulation and ANGPTL4 releasing properties may thus be promising to promote wound repair with minimizing scar formation.
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