title: Stiffness of polyelectrolyte multilayer film influences endothelial function of endothelial cell monolayer.
abstract: Endothelialization has proved to be critical for maintaining long-term success of implantable vascular devices. The formation of monolayer of endothelial cells (ECs) on the implant surfaces is one of the most important factors for the endothelialization. However, endothelial function of regenerated EC monolayer, which plays a much more important role in preventing the complications of post-implantation, has not received enough attention. Here, a vascular endothelial growth factor (VEGF)-incorporated poly(l-lysine)/hyaluronan (PLL/HA) polyelectrolyte multilayer film was fabricated. Through varying the crosslinking degree, stiffness of the film was manipulated, offering either soft or stiff film. We demonstrated that ECs were able to adhere and proliferate on both soft and stiff films, subsequently forming an integrated EC monolayer. Furthermore, endothelial functions were evaluated by characterizing EC monolayer integrity, expression of genes correlated with the endothelial functions, and nitric oxide production. It demonstrated that EC monolayer on the soft film displayed higher endothelial function compared to that on the stiff film. Our study highlights the influence of substrate stiffness on endothelial function, which offers a new criterion for surface design of vascular implants.
authors.affiliation: MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chang
authors.affiliation: MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Hu
authors.affiliation: MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Jia-Yan
authors.initials: JY
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Bo-Chao
authors.initials: BC
authors.lastname: Li
authors.affiliation: MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address: renkf@zju.edu.cn.
authors.forename: Ke-Feng
authors.initials: KF
authors.lastname: Ren
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal.
authors.forename: M Cristina L
authors.initials: MC
authors.lastname: Martins
authors.affiliation: INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal.
authors.forename: Mário A
authors.initials: MA
authors.lastname: Barbosa
authors.affiliation: MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address: jijian@zju.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D058578:Biglycan / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D055119:Elastic Modulus; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006244:Hardness; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D008567:Membranes, Artificial; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D000071228:Polyelectrolytes / Q000737:chemistry / Q000494:pharmacology*; D011107:Polylysine / Q000737:chemistry / Q000494:pharmacology*; D013499:Surface Properties; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D058578:Biglycan; D015820:Cadherins; D024141:Collagen Type IV; D005353:Fibronectins; D006820:Hyaluronic Acid; D008567:Membranes, Artificial; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000071228:Polyelectrolytes; D011107:Polylysine; D042461:Vascular Endothelial Growth Factor A; D000099152:Cadherin 5; C467484:VEGFA protein, human; C496314:NOS3 protein, human
keywords: Endothelial cell; Endothelial function; Polyelectrolyte multilayer films; Substrate stiffness; Vascular endothelial growth factor