title: Cooperative control of blood compatibility and re-endothelialization by immobilized heparin and substrate topography.
abstract: A wide variety of environmental cues provided by the extracellular matrix, including biophysical and biochemical cues, are responsible for vascular cell behavior and function. In particular, substrate topography and surface chemistry have been shown to regulate blood and vascular compatibility individually. The combined impact of chemical and topographic cues on blood and vascular compatibility, and the interplay between these two types of cues, are subjects that are currently being explored. In the present study, a facile polydopamine-mediated approach is introduced for immobilization of heparin on topographically patterned substrates, and the combined effects of these cues on blood compatibility and re-endothelialization are systematically investigated. The results show that immobilized heparin and substrate topography cooperatively modulate anti-coagulation activity, endothelial cell (EC) attachment, proliferation, focal adhesion formation and endothelial marker expression. Meanwhile, the substrate topography is the primary determinant of cell alignment and elongation, driving in vivo-like endothelial organization. Importantly, combining immobilized heparin with substrate topography empowers substantially greater competitive ability of ECs over smooth muscle cells than each cue individually. Moreover, a model is proposed to elucidate the cooperative interplay between immobilized heparin and substrate topography in regulating cell behavior.
authors.affiliation: Department of Mechanical and Aerospace Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Mechanical and Aerospace Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.affiliation: Key Laboratory of Advanced Technology of Materials, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, China.
authors.forename: Zhilu
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Key Laboratory of Advanced Technology of Materials, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, China.
authors.forename: Rifang
authors.initials: R
authors.lastname: Luo
authors.affiliation: Key Laboratory of Advanced Technology of Materials, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Key Laboratory of Advanced Technology of Materials, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Huang
authors.affiliation: Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong; Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong; State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
authors.forename: Pingbo
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Mechanical and Aerospace Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong. Electronic address: meleng@ust.hk.
authors.forename: Yang
authors.initials: Y
authors.lastname: Leng
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D002448:Cell Adhesion / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008422:Materials Testing; D010314:Partial Thromboplastin Time; D010641:Phenotype; D056951:Photoelectron Spectroscopy; D010973:Platelet Adhesiveness / Q000187:drug effects; D022502:Stress Fibers / Q000187:drug effects; D013499:Surface Properties
chemical_list: D006493:Heparin
keywords: Blood compatibility; Endothelial cell; Heparin; Substrate topography