Effects Of Polymer Chemical Property And Surface Topography On Endothelial Cell Adhesion

Biocompatibility is an important property of biomaterials depending on the interaction of material with biological environment. In vivo, within seconds after exposure to blood or serum, proteins adsorb to the material. Cells then attach via interaction of their integrins with the proteins on the surface. Growing evidence indicates that protein adsorption and cell behaviour, including cell adhesion, migration, proliferation, secretion and gene expression, can be influenced by the material chemical property and surface topography. Therefore, in the fields of biomaterials and tissue engineering, it is of great importance to study the effects of material chemical property and surface topography on protein adsorption and cell behaviour.Vascular endothelial cells, living in the whole circulatory system, are the primary cell type orchestrating the construction of blood vessels and have been widespreadly investigated due to their normal functions, including the control of contraction and relaxation of blood vessel, blood coagulation, smooth muscle cells and leukocyte traffic to extravascular tissues. Thus endothelial cell adhesion and proliferation play an important role in design of blood-compatible materials. In the work presented here, the effects of polymer chemical property and surface topography on protein adsorption and endothelial cell adhesion were systematically investigated, and a new method of surface modification for selective endothelial cell adhesion was provided. The main contents are as follows:1. In the study of the effect of polymer chemical property on protein adsorption and endothelial cell adhesion, two types of polymer with different chemical property, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)(PHBHHx) and polyurethane (PU), were chosen. Flat PHBHHx and PU surfaces were prepared. Protein adsorption was measured by radiolabeling from single protein solution. The results suggested that protein adsorption on the two types of surfaces was almost the same. In the competitive adsorption of fibrinogen (Fg) and human serum albumin (HSA) from human plasma, Fg adsorption on the two types of surfaces was similar and a prominent Vroman peak was shown at approximately0.1%plasma. However, HSA adsorption was different, indicating that polymer chemical property could impact on the competitive adsorption.Results of immunoblot and enzyme-linked immunosorbent assay indicated that the adsorption of most types of plasma protein on PHBHHx and PU was similar. But compared with PU, PHBHHx adsorbed more coagulation proteins (factor XI and prothrombin), less anticoagulation proteins (protein S) and more factor B, indicating that PHBHHx has the potential to accelerate blood clotting and cause inflammation and to become a novel wound healing and hemostasis material.Extracellular matrix protein (fibronectin and vitronectin) adsorption on PHBHHx and PU was similar. And these two types of surfaces with different chemical property also had similar endothelial cell adhesion, which might be the results of similar cell-adhesive protein adsorption on the both of surfaces, since protein adsorption was quite significant for cell adhesion. This chapter provides theoretical guidance for deep understanding and full playing of the biological perfermance of PHBHHx and PU, and has the practical application value.2. In the study of the effect of polymer surface topography on protein adsorption and endothelial cell adhesion, lotus leaf-like topography was introduced onto PU, PU/pluronic blends (PU/P) and PHBHHx via replica molding using a natural lotus leaf as the template. Water contact angle measurements showed that both the hydrophobicity of the PU and PHBHHx surface and the hydrophilicity of the PU/P surface were enhanced by the construction of lotus leaf-like topography. Protein adsorption on the PU/P surface without topographical modification was significantly lower than on the PU surface. And the adsorption was further reduced when lotus leaf-like topography was constructed on the PU/P surface. The PU/P surface with lotus leaf-like topography thus appears to be resistant to nonspecific protein adsorption derived from the both chemical property and surface topography.Endothelial cell and fibroblast adhesion and proliferation were reduced on the lotus leaf-like PHBHHx (PHBHHx-L) compared to the flat polymer surface. These results suggest that the inhibition of cell adhesion and proliferation caused by the lotus leaf-like topography nullifies the effect of the adsorbed adhesive proteins in promoting adhesion and proliferation. It can be concluded that the lotus leaf-like topography plays a dominant role in the interaction between Cells and PHBHHv-T The lotus leaf-like topography showed a higher inhibition on the proliferation of endothelial cells than that on fibroblasts. This chapter provides the theoretical guidance for deep understanding of the relationship between protein, cell and material surface topography, and has potential application prospect.3. Rapid endothelialization on the surface of cardiovascular implants is a promising way to solve the problems of the vascular restenosis. In the study of material surface for endothelial cell selective adhesion, a poly[oligo (ethylene glycol) methyl ether methacrylate]-block-poly(glycidyl methacrylate)(POEGMA-b-PGMA) diblock copolymer was grafted on silicon wafer surface via surface-initiated atom transfer radical polymerization (SI-ATRP), and endothelial specific peptide Glycine-Arginine-Glutamic acid-Aspartic acid-Valine-Tyrosine (GREDVY) was conjugated through the epoxy groups opening in PGMA segments. Surface grafting of POEGMA-b-PGMA diblock copolymer and conjugation of GREDVY, were demonstrated by water contact angle, ellipsometry, X-ray photoelectron spectroscopy (XPS) and atomic force microscope (AFM) measurements. Results of cell adhesion experiments indicated that the surface modified with GREDVY conjugated diblock copolymer could effectively repel fibroblasts adhesion while promoting endothelial cells adhesion. This study provides an effective method of surface modification for selective endothelial cell adhesion.