| With the rapid development of fabricating technology of biomaterials,as well as development of the surface characterization and inspection approach,biomaterials are nowadays more functional and intellengent.Biomaterials are designed to stimulate specific cellular responses at molecular level.In the field of hard tissue replacement,the requirement to improve the biological properties of biomaterials,such as osseointegration,has been increased as a result of the increasing desire of the bonereplacement surgery.Therefore,in order to induce cell function in response to special reaction and to form new tissues,biomaterials should be carefully designed and fabricated to meet the ability of molecular recognition.It is becoming a crucial issue that need to be solved urgently in the research of tissue engineering.Titanium and its alloys,which are commonly used biomedical metal materials,have wide applications in the field of hard tissue replacement.Surface modification for titanium based biomaterials under proper treatment,can be a promising way to enhance its biocompability.Among all kinds of factors which could insert an influence on the interaction of tissues/cells-biomaterials,surface topography is an independent character to affect cell behavior.Investigation on the mechanism of inducing and controlling cell behaviors as a function of surface micro-/nano-topography,is an important prerequisite during the design of biomaterials.Based on the important character of ECM proteins in mediating cell adhesion,investigation of interaction between ECM proteins and biomaterials is of great importance to reveal the mechanism of cell adhesion.In this work,in order to explore the mechanism of interactions between cells and biomaterials,both cell assays and molecular simulations were conducted.The influence of surface tupography on cell behaviors was analyzed,and effects of surface topography on adsorption of ECM proteins should be studied in order to provide experimental and theoretical directions to explore the cell-material interaction.Since surface topography could be an independent factor that inserts an effect on cell behavior,the behaviors of MC3T3-E1 osteoblast cells,such as adhesion and proliferation in response to surface roughness on the Ti6Al7 Nb substrate were analyzed.The “contact guidance” phenomenon of osteoblasts as a function of grooves dimensions on PDMS surface was also studied.Our results suggested that abilities of cell spread and proliferation were inhibited on titanium alloy surface as the surface roughness increased.As the depth of grooves on PDMS surface increased,the “contact guidance” phenomenon was strengthened.However,the phenomenon was less favored as the groove width decreased,where osteoblasts were observed to bridge the grooves.We found the protrusion of cell filopodias around osteoblasts was restricted as a result of surface micro-/nano-topography,which actually induced certain cell behaviors,such as “contact guidance”.Nano-structured titanium substrate may be volunteered to become hydroxylated if exposed in aqueous solution,which could insert an effect on cell adhesion and protein adsorption.In this work,the hydroxylated models of rutile TiO2 substrates with step structures were built up via the density functional theory calculations.The surface energy density at the step structures parallel to the <11—1> crystal direction on TiO2(110)surface has a higher value,which could be active sites for water dissociation.The atomic structures and the molecular force field of the hydroxylated step structures were obtained.The dynamic procedure of water dissociation at the step structures was studied and the results suggest that the free proton generated after dissociation could be captured by the unsaturated oxygen atoms near the step edges.At higher water coverage,the free proton could also diffuse to the aqueous solution in the form of hydronium(H3O+).Based on the hydroxylated models,distribution of water molecules on TiO2 surface was also investigated via the classical molecular dynamics simulation method.The results revealed that the layed water molecules on TiO2 surface were weakened on hydroxylated substrates compared to the non-hydroxylated substrates.In order to study the adsorption properties of ECM proteins on nano-structured TiO2 surface,in this work,adsorption model about collagen and the tripeptide,i.e.,Gly-Hyp-Pro,on rutile TiO2 surface was set up.The effects of surface atomic steps and grooves on collagen adsorption were investigated by means of classical molecular dynamics simulation method.Our results suggest that water molecules on TiO2 surface could provide active sites for collagen adsorption,however,the dense water molecules inside the grooves in turn could be barriers for collagen adsorption.The dynamics during the adsorption of tripeptide on the neutral fully hydroxylated TiO2 and on the negatively charged fully hydroxylated TiO2 surface were compared,during which the free energy and binding energy of tripeptide were analyzed.The adsorption of tripeptides on grooved substrates with and without surface hydroxylation were also studied and compared,and the results suggested that water molecules inside the grooves could be less layered and more loosened due to the surface hydroxylation,which increased the possibility of tripeptides diffusing into the grooves.In order to analyze the effects of calcium/phosphate ions inserted on the adsorption procedure of tripeptide,the molecular structures of HPO42-and H2PO4-anions were built up.The aggregation of calcium/phosphate ions on TiO2 surface was studied and the nucleation of the Ca-P clusters were favored on the hydroxylated TiO2 surface.The nano-structures on the TiO2 surface could restrict the diffusion of calcium/phosphate ions and provide active sites for ion adsorption at the same time,which could enhance the mineralization of calcium phosphate clusters eventually.The dynamics during adsorption and the free energy change of calcium cations on TiO2 surface were analyzed,and the adsorption conformation of calcium cations and phosphate anions on TiO2 surface were studied.Adsorption of tripeptide on the hydroxylated TiO2 surface assisted by the calcium cations was also studied.In solution,calcium/phosphate ions have higher diffusion ability compared with that of tripeptides,therefore,calcium/phosphate ions could reach the TiO2 surface firstly,meanwhile providing active sites for the adsorption of tripeptides.When surface grooves were exposed in solution,calcium/phosphate ions could aggregate inside the grooves rapidly,eventually promoting the adsorption of tripeptides inside grooves.By investigating the effects of surface characters including topography and hydroxylation,on the adsorption of collagen and the tripeptide,this work could provide theoretical basis for designing and fabricating surface topographies of biomaterials. |
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