| With the rapid development of global desire for bone instruments, to search and produce implanted materials with excellent bone conduction, incentive and reconstruction has become a hot topic in the area of life science, biomaterials and micro-nanomachining. Titanium (Ti) and Ti-alloy are extremely popular in the application of implanted materials, since they are characterized by low elastic modulus, high erosion resistant, good chemical stability, and a density close to human bone. However, the long-term clinical researches indicated that the bone could not be reconstructed efficiently on the surface of Ti and Ti-alloy implants, which made the implants hard to be integrated with the surrounding bony tissue. Therefore, to further improve the biocompatibility of Ti and Ti-alloy implants, it seems quite important to modify their surface with biotechnology, which will help to accelerate the full integration between implanted materials and the interface of living tissue in human body.Among the various technologies for surface biomodification, biomimetic pre-coating with bioadhesive and proliferative factors has attracted special attentions of many researchers. The pre-interposition of biomimetic coating, e.g., specific extracelluar matrix (ECM) adhesive proteins, between the substrate and the cell environment hinders the unspecific adsorption of proteins from the blood. That is, the response from cells to the implanted materials mainly depends on the type, conformation, density and orientation of surface-bound proteins, whereas the characteristic of implanted surface, especially the nano-scale topography, which may influence the cellular response, can only be expressed indirectly via the distribution of pre-coating protein layer. Hence, the adsorption behavior and bioactivity of ECM adhesive proteins can be optimized and regulated by controlling the surface topographies of implanted materials, which will help to make the ECM proteins act as a bridge between the implant and the cell environment. However, the effect of surface topographies on protein adsorption involves a huge number of factors; thus it seems unreasonable to gain the optimum condition solely by repeated experiments. In order to construct a biofunctionalized interface suitable for cell adhesion, spreading, proliferation and differentiation, we need to understand the underlying micro-mechanism of the effect of surface topographies on the adsorption behavior of protein at a molecular level, which will be regarded as the guidance for the design of surface. Therefore, the dissertation focused on the influencing mechanism of surface topographies and hydroxylation of substrate, as well as solution elements on the adsorption behavior of peptide, with the following works finished by means of molecular dynamics (MD) simulation.The property of medium water is one of the main determinants of successful biofunction for the biomolecules; thus the dissertation began with the selection of an appropriate water model. The time needed for the Argine-Glycine-Aspartic acid (Arg-Gly-Asp, RGD) sequence to achieve adsorption equilibration onto the neutrally charged nonhydroxylated rutile (110) surface was compared quantitatively with the adsorbate and adsorbent solvated in TIP3P and SPC/E waters, respectively. On the basis of the mentioned comparison and the similarity of bulk physical properties of water models to the true liquid, the preferred water model was selected.To test all the possible binding modes between RGD and the substrate surface, the peptide functional groups inclined to directly interact with the rutile surface were determined in case of spontaneous RGD deposition with various initial configurations. Meanwhile, the possibility of direct bonding between the carboxyl groups of RGD and the surface atoms of substrate was also validated under the condition that an external force was involved in setting the initial state of peptide. Local grooves with different depths were introduced to systematically investigate the effect of surface topography on the binding mode of peptide and to find out the dominant factor determining the binding strength of RGD–rutile complex.Referring to the charged property of substrate in the pH environment of blood, we constructed the negatively charged hydroxylated and nonhydroxylated rutile surfaces, with the surface charges neutralized by adding cations to the simulation solvent. The affinities of different groups on the negatively charged hydroxylated rutile surfaces were discussed, and the bulk properties of involved cations, as well as the trend of distribution in the rutile–water interface were analyzed. Furthermore, the dominant binding sites for both monovalent (Na+, K+, and Rb+) and divalent cations (Mg2+, Ca2+, and Sr2+), together with the relationship between the adsorption strength and the lyotropic sequence were determined. Since Na+is the most abundant inorganic ion in blood plasma, it was selected first to study the influence of cation on Asp–rutile interaction (both carried a net negative charge) and Arg–rutile interaction (they carried opposite net charges). A comprehensive analysis was subsequently made to explain the influence of surface hydroxylation, charges and binding modes of mediating cations on the adsorption behavior of RGD sequence onto rutile surfaces.RGD, which can identify and bind to the integrin receptors located on the surface of cell membrane, is the most important short peptide in fibronectin. However, the isolated RGD motif cannot completely inspire the integrin-mediated signaling mechanisms, which is induced by a whole fibronectin molecule. Therefore, the target peptide was extended to fibronectin segment (the tenth type III module of fibronectin, FN-III10) on the basis of a detailed analysis of adsorption mechanism for short peptide. The focus of the last part of the dissertation was to address the response activity of protein segment to the nano-scale topographical features of the substrate. The adsorption priorities of FN segment onto the surfaces with different superficial defects (oxygen vacancy, step, and rectangular groove) or nanostructures (budding, cavity, and plow groove) were obtained, and the influencing law of surface nano-topographies on the adsorption stability of protein segment was proposed. For the FN-III10solvated in NaCl solution, the forces driving the protein–rutile binding were analyzed and the inherent factors influencing the permanence of Na+mediation in protein adsorption onto the negatively charged hydroxylated/nonhydroxylated rutile surfaces were identified. |
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