PMID- 30676736
OWN - NLM
STAT- MEDLINE
DCOM- 20190617
LR  - 20190617
IS  - 1944-8252 (Electronic)
IS  - 1944-8244 (Linking)
VI  - 11
IP  - 7
DP  - 2019 Feb 20
TI  - Stiffness of Aligned Fibers Regulates the Phenotypic Expression of Vascular 
      Smooth Muscle Cells.
PG  - 6867-6880
LID - 10.1021/acsami.9b00293 [doi]
AB  - Electrospun uniaxially aligned ultrafine fibers show great promise in 
      constructing vascular grafts mimicking the anisotropic architecture of native 
      blood vessels. However, understanding how the stiffness of aligned fibers would 
      impose influences on the functionality of vascular cells has yet to be explored. 
      The present study aimed to explore the stiffness effects of electrospun aligned 
      fibrous substrates (AFSs) on phenotypic modulation in vascular smooth muscle 
      cells (SMCs). A stable jet coaxial electrospinning (SJCES) method was employed to 
      generate highly aligned ultrafine fibers of poly(l-lactide- 
      co-caprolactone)/poly(l-lactic acid) (PLCL/PLLA) in shell-core configuration with 
      a remarkably varying stiffness region from 0.09 to 13.18 N/mm. We found that 
      increasing AFS stiffness had no significant influence on the cellular shape and 
      orientation along the fiber direction with the cultured human umbilical artery 
      SMCs (huaSMCs) but inhibited the cell adhesion rate, promoted cell proliferation 
      and migration, and especially enhanced the F-actin fiber assembly in the huaSMCs. 
      Notably, higher fiber stiffness resulted in significant downregulation of 
      contractile markers like alpha-smooth muscle actin (alpha-SMA), smooth muscle myosin 
      heavy chain, calponin, and desmin, whereas upregulated the gene expression of 
      pathosis-associated osteopontin ( OPN) in the huaSMCs. These results allude to 
      the phenotype of huaSMCs on stiffer AFSs being miserably modulated into a 
      proliferative and pathological state. Consequently, it adversely affected the 
      proliferation and migration behavior of human umbilical vein endothelial cells as 
      well. Moreover, stiffer AFSs also revealed to incur significant upregulation of 
      inflammatory gene expression, such as interleukin-6 ( IL-6), monocyte 
      chemoattractant protein-1 ( MCP-1), and intercellular adhesion molecule-1 ( 
      ICAM-1), in the huaSMCs. This study stresses that although electrospun aligned 
      fibers are capable of modulating native-like oriented cell morphology and even 
      desired phenotype realization or transition, they might not always direct cells 
      into correct functionality. The integrated fiber stiffness underlying is thereby 
      a critical parameter to consider in engineering structurally anisotropic 
      tissue-engineered vascular grafts to ultimately achieve long-term patency.
FAU - Yi, Bingcheng
AU  - Yi B
AUID- ORCID: 0000-0001-8056-4882
FAU - Shen, Yanbing
AU  - Shen Y
FAU - Tang, Han
AU  - Tang H
FAU - Wang, Xianliu
AU  - Wang X
FAU - Li, Bin
AU  - Li B
AD  - Department of Orthopaedics , The First Affiliated Hospital of Soochow University 
      , Suzhou 215006 , China.
AD  - Orthopaedic Institute, Medical College , Soochow University , Suzhou 215007 , 
      China.
AD  - China Orthopaedic Regenerative Medicine Group (CORMed) , Hangzhou 310058 , China.
FAU - Zhang, Yanzhong
AU  - Zhang Y
AUID- ORCID: 0000-0002-2663-1279
AD  - China Orthopaedic Regenerative Medicine Group (CORMed) , Hangzhou 310058 , China.
LA  - eng
PT  - Journal Article
DEP - 20190206
PL  - United States
TA  - ACS Appl Mater Interfaces
JT  - ACS applied materials & interfaces
JID - 101504991
RN  - 0 (Muscle Proteins)
RN  - 0 (Polyesters)
RN  - 459TN2L5F5 (poly(lactide))
SB  - IM
MH  - *Cell Proliferation
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Muscle Proteins/*biosynthesis
MH  - Muscle, Smooth, Vascular/cytology/*metabolism
MH  - Myocytes, Smooth Muscle/cytology/*metabolism
MH  - Polyesters/chemistry
MH  - Tissue Engineering
MH  - Tissue Scaffolds/*chemistry
OTO - NOTNLM
OT  - contractile phenotype
OT  - electrospun aligned fibers
OT  - macrophage-like phenotype
OT  - shell-core structure
OT  - stiffness
OT  - vascular smooth muscle cells
EDAT- 2019/01/25 06:00
MHDA- 2019/06/18 06:00
CRDT- 2019/01/25 06:00
PHST- 2019/01/25 06:00 [pubmed]
PHST- 2019/06/18 06:00 [medline]
PHST- 2019/01/25 06:00 [entrez]
AID - 10.1021/acsami.9b00293 [doi]
PST - ppublish
SO  - ACS Appl Mater Interfaces. 2019 Feb 20;11(7):6867-6880. doi: 
      10.1021/acsami.9b00293. Epub 2019 Feb 6.