TY - JOUR
T1 - Regulation of migratory activity of human keratinocytes by topography of multiscale collagen-containing nanofibrous matrices
AU - Fu, Xiaoling
AU - Xu, Meng
AU - Liu, Jie
AU - Qi, Yanmei
AU - Li, Shaohua
AU - Wang, Hongjun
PY - 2014/2
Y1 - 2014/2
N2 - 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±112nm) 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±26nm). 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.
AB - 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±112nm) 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±26nm). 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.
KW - Human keratinocytes
KW - Integrin β1
KW - Laminin-332 (laminin-5)
KW - Nanofibers
KW - Reepithelialization
KW - Topography
UR - http://www.scopus.com/inward/record.url?scp=84890185307&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84890185307&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2013.11.013
DO - 10.1016/j.biomaterials.2013.11.013
M3 - Article
C2 - 24268197
AN - SCOPUS:84890185307
SN - 0142-9612
VL - 35
SP - 1496
EP - 1506
JO - Biomaterials
JF - Biomaterials
IS - 5
ER -