title: Regulation of migratory activity of human keratinocytes by topography of multiscale collagen-containing nanofibrous matrices.
abstract: Nanofibrous matrices hold great promise in skin wound repair partially due to their capability of recapturing the essential attributes of native extracellular matrix (ECM). With regard to limited studies on the effect of nanofibrous matrices on keratinocytes, the present study was aimed to understand how the topographical feature of nanofibrous matrices regulates keratinocyte motility by culturing keratinocytes on polycaprolactone (PCL)/collagen nanofibrous matrices (rough surface with fiber diameters of 331 ± 112 nm) or the matrices coated with a thin layer of collagen gel to form a secondary ultrafine fibrous network (smooth surface with ultrafine fiber diameters of 55 ± 26 nm). It was found that the PCL/collagen nanofibrous matrices alone did not stimulate cell migration, while collagen gel coating could significantly increase cell motility. Further studies demonstrated that the ultrafine fibrous network of collagen gel coating significantly activated integrin β1, Rac1 and Cdc42, facilitated the deposition of laminin-332 (formerly called laminin-5), and promoted the expression of active matrix metalloproteinases (MMPs) (i.e., MMP-2 and 9). Neutralization of integrin β1 activity abrogated the gel coating-induced keratinocyte migration. These findings provide important evidence on the role of topographical features of nanofibrous matrices in regulating the phenotypic alteration of keratinocytes and suggest the possible utility of collagen-containing nanofibrous matrices for skin regeneration especially in re-epithelialization.
authors.affiliation: Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA; The National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510640, People's Republic of China; The School of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, People's Republic of China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Surgery, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Surgery, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Surgery, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA. Electronic address: Hongjun.Wang@stevens.edu.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wang
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D057139:Nanofibers; D011091:Polyesters; D054457:Tissue Scaffolds; D015854:Up-Regulation
chemical_list: D019012:Integrin beta1; D007797:Laminin; D011091:Polyesters; C016240:polycaprolactone; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Human keratinocytes; Integrin β1; Laminin-332 (laminin-5); Nanofibers; Reepithelialization; Topography