Research On The Preparation Of Ions Doped Inorganic Bioactive Self-setting Materials And Their Application In Dental Pulp Repair

Due to caries,trauma,etc.,it will cause the destruction of the tooth structure,which may further lead to the exposure,damage and even necrosis of the pulp tissue.However,the special nature of teeth makes it difficult to heal after injury,it is necessary to carry out subsequent endodontic treatment.At present,the materials mainly used in clinical practice still have some drawbacks such as long setting time,poor operational performance,and single function,which cannot fully satisfy the requirements of pulp regeneration and repair.Rapid self-setting materials that have both great biological activity and can be shaped arbitrarily can better meet clinical needs.Bioactive glass has been widely used in bone defect repair because of its excellent osteoconduction and osteoinduction properties.In recent years,researches have also found that bioactive glass has good potential for pulp regeneration and repair applications.However,current researches still focus on the repair mechanism of bioactive glass powder,which cannot meet the operational and functional requirements for pulp regeneration and restoration.In this study,novel inorganic bioactive glass cement（BGC）was prepared based on the sol-gel bioactive glass（SBG）powder.The material has the properties of fast self-setting and the ability to induce dental pulp regeneration;the physicochemical properties and curing mechanism of BGC has been discussed in detail,which can also be expected to achieve the setting for a wider range of bioactive glass materials.Moreover,functional magnesium and strontium ions had been successful doped into SBG powders,the effects of strontium and magnesium ions substitution on the physicochemical properties of bioactive glass powder and BGC had also been investigated,as well as their effects on promoting the odontogenic differentiation of human dental pulp stem cells（DPSCs）,angiogenesis,and reparative dentin formation.The main research work and conclusions are as follows:（1）Based on the sol-gel bioactive glass（SBG）,novel inorganic bioactive glass cement（BGC）with fast-setting,anti-washout and good operability was successful prepared by compounding DCPD and phosphate solution with appropriate proportion.We found that the content of SBG in BGC,both the type and concentration of phosphate,the calcium content in SBG,and the preparation method of BG had an impact on the physicochemical properties of BGC;through in-depth analysis of the setting reaction mechanism of BGC,it was found that the setting process of BGC was consistent with the apatite formation process on BG powders,and the factors affecting the apatite formation on BG powder would also affect the setting reaction of BGC.Based on this setting mechanism,further self-setting of more extensive bioactive glass materials was expected to be achieved.The cytological evaluation indicates that the 40B cement with the best physical and chemical properties had good cell compatibility and promoted the odontogenic differentiation of DPSCs,indicating that the BGC had good potential for dental pulp repair.（2）Magnesium-doped bioactive glass（Mg-SBG）powders with different magnesium contents were prepared by partially or completely substitute calcium with magnesium based on SBG.The substitution of magnesium ions has little effect on the phase and morphology for Mg-SBG powders,but it could inhibit the apatite formation ability of Mg SBG powders in vitro.The substitution of magnesium ions had little effect on the cell compatibility of Mg-SBG powders;The incorporation of magnesium in SBG powders had a concentration dependent effect on the promotion of odontogenic differentiation and 36Mg-SBG powder with calcium completely replaced by magnesium significantly inhibited odontogenic differentiation;The substitution of magnesium ions in SBG powders enhanced the angiogenesis effect.（3）Magnesium-doped bioactive glass cement（Mg-BGC）was prepared with based on Mg-SBG powders and 40B cement.As the magnesium content increased,magnesium participated in regulating the formation of HA phase and directly setting reaction to form KMg PO₄·6H₂O phase.The two curing reactions comprehensively affected the setting properties,ion release,and in vitro degradation of Mg-BGC.What’s more,Mg-BGC with different magnesium contents exhibited good cell compatibility.The substitution of magnesium in Mg-BGC also had a concentration dependent effect for promoting odontogenic differentiation;Mg-BGC had a significant promoting effect on vascular regeneration for high content substitution of magnesium.The promotion of odontogenic differentiation and angiogenesis of Mg-SBG powder and Mg-BGC had a certain corresponding relationship.Overall,high content magnesium（15 Mg）had the best effect on promoting odontogenic differentiation and angiogenesis.（4）Strontium-doped bioactive glass-ceramic（Sr-SBG）powders with different amounts of strontium（calcium partially substituted to completely substituted with strontium）had been successfully prepared.The substitution of strontium in Sr-SBG increased the tendency of Sr₂Si O₄ crystal phase and decreased the specific surface area and mesoporous size;the low amount of strontium（5Sr）doping would improve the apatite forming ability of Sr-SBG,while a higher content of strontium（10-36 Sr）doping inhibited the formation of apatite and strontium would enter the apatite phase after doping;the substitution of strontium in SBG powders had little effect on cell compatibility,but had a concentration dependent effect on the odontogenic differentiation of DPSCs.The substitution of a small amount of strontium（5Sr）could enhance the promoting odontogenic differentiation effect of SBG powder,while the high content substitution of strontium（15-36 Sr）would delay the promoting odontogenic differentiation effect of SBG.（5）Strontium-doped bioactive glass-ceramic based cement（Sr-BGC）had been prepared by Sr-SBG powder.Strontium doping would reduce the curing reaction rate of BGC and formed strontium partially substituted apatite.Sr₂Si O₄ phase in Sr-BG were also able to set with DCPD and the setting reaction affect the curing and phase properties of Sr-BGC.Strontium doping had little effect on the degradation of Sr-BGC in vitro.All Sr-BGC doped with different concentrations of strontium exhibited good cell compatibility;the incorporation of low content strontium（5-10 Sr）enhanced the in vitro odontogenic differentiation effect of BGC,while the substitution of high content strontium（15-25 Sr）reduced the odontogenic differentiation effect of BGC;the effect of strontium doping on the physicochemical properties and in vitro odontogenic differentiation effect of Sr-BG powder and Sr-BGC was basically consistent.The incorporation of low content strontium（5Sr）simultaneously improved the odontogenic differentiation effect of SBG powders and BGC.The results of in vivo direct pulp capping experiments indicated that BGC could promote the formation of regenerated dentin,and strontium doping further enhanced the reparative dentin formation of BGC.Based on both in vivo and in vitro experimental results,a small amount of strontium-doped 5Sr-BGC was more suitable for pulp repair.In summary,based on sol-gel bioactive glass and functional ion substitution,our research realized the self-setting of sol-gel bioactive glass powders,further clarified the self-setting mechanism of bioactive glass cement,and the self-curing of a wider range of bioactive glass materials was expected to realize.Combined with magnesium and strontium ion substitution,the effects of magnesium and strontium doping on the odontogenic differentiation,angiogenesis and reparative dentin of bioactive glass cement were explored.The research of bioactive glass-based self-curing materials provides a new option for the clinical application of bioactive glass in pulp repair,and even in bone tissue defect repair,while the physicochemical properties and biological results of ion-doped bioactive glass powder could also provide theoretical guidance for other types of bioactive glass self-setting materials.