Surface Functionalization Of Titanium By Cations Substituted Hydroxyapatite To Promote Bone Osseointegration

The innate bio-inert nature of titanium?Ti?can lead to poor bonding between implants and surrounding tissues,resulting in the final failure of impants.In order to meet clinical requirements,traditional hydroxyapatite?HA?coating should also be modified to improve its biological performance,such as poor in vivo degradation rate and low osseoinductivity.To solve the above problems,this work systematically studies the following issues:?1?HA was modified by dual doping of both Mg²⁺and Sr²⁺to substitute Ca²⁺partially through hydrothermal method.Then,the effects of cation substitution on the physicochemical properties and growth mechanism were discussed in detail.Furthermore,the in vitro biological performances were evaluated.?2?Sr²⁺and Ag⁺co-substituted HAs were prepared by hydrothermal deposition.Their physicochemical properties,in vitro biological performances and antibacterial properties were evaluated.Meanwhile,the action mechanisms of Sr²⁺and Ag⁺were studied.?3?Ti-based microRNA nanocapsules with HA or SrHA composite coatings were prepared by hydrothermal deposition and in-situ polymerization.The physicochemical properties,releasing behaviors,in vitro and in vivo biological performances of the coatings were evaluated.In addition,the action mechanisms of microRNA,HA and SrHA were discussed.?4?Ti-based biomimetic micro-nano structure was prepared by electrochemical corrosion method.After deposition of SrHA and microRNA coating,the in vitro and in vivo biological properties were evaluated,respectively.Moreover,the mechanism was explored.Based on the above studies,we get the following results?1?Mg²⁺,acted as an unstable substituent,could decrease the crystallinity,lattice parameters,crystal size and thermostability.Meanwhile,it could be adsorbed on the surface of HA and inhibited the grain growth.The critical concentration of Mg²⁺for the transition from the crystal to amorphous phase was 30%.The incorporation of Sr²⁺could increase the lattice parameters and slightly decrease the crystallinity of HA.The incorporation of Sr²⁺caused lattice distortion.The lattice distortion degree increased with the addition of Sr²⁺and reached maximum at 50%.When the content exceeded50%,the lattice distortion degree decreased with the Sr²⁺content until the grain exhibited a regular hexagonal structure again at 100%.In vitro experiment showed that cations had a dose-dependent synergetic effect on cell growth.An appropriate proportion of both Mg²⁺and Sr²⁺could play a significant role for improving the biocompatibility of HA.10Mg20Sr can accelerate the cell growth in this study.Accordingly,ES-SrHA,which prepared from egg shells with the incorporation of 20%Sr²⁺,exhibited a remarkable bioactivity.?2?Ti-based Sr²⁺and Ag⁺co-substituted coatings showed long-term sustainable Ag⁺releasing behaviors and thus antibacterial properties.Meanwhile,the presence of Sr²⁺could reduce the release concentration of Ag⁺,thereby reducing the cytotoxicity.In this study,Ti-based 10Sr0.1Ag-HA coating showed an excellent antibacterial property?99%for E.coli,95%for S.aureus?and comparable cell proliferation and enhanced cell differentiation with respect to pure Ti.?3?Ti-based miR-21nanocapsule?³0nm?coating showed long-term sustainable miR-21 releasing behavior.It was beneficial to the angiogenesis and could promote bone remodeling and mineralization.In addition,Ti-based miR-21/HA composite coating further enhanced the bioactivity and mineralization rate.Moreover,Ti-based miR-21/SrHA composite coating could not only increase the bioactivity and mineralization rate,but also inhibit osteoclast viability,resulting in a remarkable improvement of osseointegration.?4?Ti-based operculiform micro-nano structure with continuous micro and nano pits,prepared by electrochemical corrosion method,showed enhanced cell growth,protein formation and mineral deposition ability.On the one hand,the osteoclast activity could be inhibited after deposition of SrHA coating.On the other hand,miR-21 coating could improve the formation of vessels.Thus,such Ti-based operculiform micro-nano structure with SrHA coating?or miR-21 coating?could promote bone mineralization and new-old bone integration,resulting in a remarkable improvement of bone-implant binding strength compared with the untreated Ti.