Surface Modification On Implants Via Layer-by-Layer Selfassembly To Introduce Bioactive Ion-Containing For Improved Bone Repairing

The extracellular matrix of natural bone is mainly composed of collagen and hydroxyapatite,which is criterion for choosing calcium phosphate-based ceramics as the mainstream component for bone repair materials or implants.Nevetheless,it is noted that the inorganic mass in native bone is not a stoichiometric hydroxyapatite,which is actually rich in various trace elements,such as Mg,Sr,Cu and Ba.These elements play important roles in the process of bone growth,with regulation effects on angiogenesis,biomineralization,and multiple physiological functions such as cell migration.From this aspect,these elements are frequently used to enhance the osteogenic activity of bone filling materials,achieving improved repair efficiency and functional reconstruction.However,the majority of commercial products currently used in clinical treatment for bone repair does not have the function of controlled release of bioactive ions.In view of this situation,this thesis takes two kinds of repairing materials used in dental restoration as the substrates,namely titanium alloy implants and bone-filled ceramic particles,to carry out the study on bioactive ions(e,g,Mg²⁺and Sr²⁺)loading and controlled releasing.Mg²⁺was selected due to its significant functions in enhancing angiogenesis and cell recruitment,while Sr²⁺was seletcted due to its function in promoting mineralization.To load the ions,a common and simple surface modification method that layer-by-layer self-assembly was applied,for which,a polycation solution and a polyanion solution are coated onto targeted substrates surface alternately with Mg²⁺and Sr²⁺being dispersed in the solution at certain concentrations..The main achievements obtained in this study are summarized as follows:（1）The modulus of titanium alloy（Ti6Al4V）is close to that of natural bone,and has good corrosion resistance and biocompatibility,which is currently the mainstream material for oral implants.However,due to the easy formation of a biologically inert layer on the surface of titanium,surface sandblasting and micro-nano treatment are often used to improve its osteogenic activity and integration with surrounding bone tissues as implanted.Herein,Ti6Al4V sheets were initially treated with hot alkali to form nanoporous surface,and then coated with hyaluronic acid solution and chitosan solution alternately,during which,different proportions of Mg²⁺and Sr²⁺were introduced into the hyaluronic acid solution.Under optimized parameters（solution concentration,layer number,vacuum）,the surface morphology of alkali-treated Ti6Al4V sheets could be well maintained,while with polymeric layers covering the surface homogeneously,showing uniformly distributed Mg²⁺/Sr²⁺.By detecting the release behaviors of the two ions,as well as the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells（BMSCs）,it was found that the surface modification of titanium alloy sheets was successfully performed by adjusting the concentration of polyanions and polycations in the solution,as well as the ion concentrations and ratios,a sustained and controllable Mg²⁺/Sr²⁺release behaviors were obtained.The modified titanium alloy sheet has good biocompatibility,particularly,when the ratio of incoporated Sr²⁺/Mg²⁺was set as 1:2,the promotion effect on the osteogenic differentiation of BMSCs was the strongest.（2）Insufficient alveolar bone volume is not conducive to the clinical application of implant surgery.Bone augmentation surgery is often performed by filling guided bone regeneration materials.Inorganic particles obtained by calcining natural animal bone is one of the main bone filling materials,and its main component is hydroxyapatite with high crystallinity,being able to provide significant osteoconductivity,while lacking of osteoinductivity.Onto the calcined inorganic particles,following the optimized coating system obtained in the aforementioned research,the layer-by-layer self-assembly of hyaluronic acid solution and chitosan solution containing 0.1 mol/L Sr²⁺and0.2 mol/L Mg²⁺,was applied.The modified bone filling particles demontrated excellent biocompatibility,and had a significant promotion effect on angiogenesis and osteogenesis,as compared to the pristine material.In summary,the layered assembly of polyanions and polycations loaded with bioactive ions is a simple and effective method to modify and upregualte the osteogenic activity of implants for bone repairing.The outcomes of this study lay a foundation for the development of a new generation of restorative materials suitable for oral treatment.