Preparation And Properties Of Injectable High-strength β-tricalcium Phosphate-based Bone Cement

As an important component of calcium phosphate cement（CPC）,β-tricalcium phosphate（β-TCP）has been extensively investigated in hard tissue repair applications due to its inorganic composition,bioresorbability and osteoconductive properties similar to those of natural bone.Although β-TCP bone cements have shown advantages such as self-curing,non-exothermic effects,plasticity and good biocompatibility,their rapid curing time,inadequate mechanical properties and slow degradation have limited their widespread use in clinical practice.In order to expand the clinical applications of β-TCP materials and β-TCP bone cements,this project firstly prepared β-TCP powders of different sizes and morphologies by CaCO3 template method and precipitation method,and explored the application potential of β-TCP microspheres with surface porous structure as drug carriers and the feasibility of the preparedβ-TCP nanoparticles for bone cement preparation,respectively.As the bone cements prepared from simple β-TCP nanoparticles have more defects,the systematic study of bioactive glass（BG）,γ-glutamic acid（γ-PGA）,wheat gluten（WG）and hemihydrate was carried out in response to the clinical requirements for bone cement properties.The effects of calcium sulfate hemihydrate（CSH）on the workability,mechanical strength,in vitro degradation,in vitro bioactivity and biocompatibility of β-TCP bone cements.The results show that the β-TCPbased bone cements were not only significantly improved in terms of workability and mechanical strength,but also in terms of in vitro degradability,in vitro bioactivity and biocompatibility.The paper concludes with a discussion of the clinical potential and significance of the prepared β-TCP-based bone cement as a reinforcing agent for vertebral body kyphoplasty,using Polymethylmethacrylate（PMMA）bone cement,which is currently widely used in clinical practice,as a control group.The main research elements of the thesis are as follows:（1）Preparation and characterization of β-TCP powderIn this section,β-TCP with different sizes and morphologies were successfully prepared by two methods,namely CaCO3 template method and chemical precipitation method,and the effects of the preparation methods and process parameters on the morphology,size,crystalline phase and crystallinity of β-TCP were investigated.The results showed that the average diameter of the β-TCP microspheres obtained by the CaCO3 template method was 15.7±1.3μm and had a tunable surface porous structure.The surface porous structure of the β-TCP microspheres showed potential application as drug carriers,which is important for expanding the application of β-TCP materials in the biological field.Furthermore,the β-TCP nanoparticles obtained by chemical precipitation method have fibrous,hexagonal and granular structures.The feasibility of preparing bone cement from granular β-TCP nanoparticles was confirmed by pre-experiments.However,the bone cement prepared from pure β-TCP nanoparticles suffers from poor handling properties,poor anti-collapse ability and insufficient mechanical properties.（2）Preparation and characterization of high strength injectable β-TCP composite bone cementThis part firstly prepared magnesium-strontium-doped BG nanospheres by sol-gel method,and systematically investigated the effects of different contents of magnesiumstrontium-doped BG nanospheres on the operability and mechanical properties of β-TCP bone cement,and determined that β-TCP bone cement showed better operability and mechanical compression strength when the fraction of BG and β-TCP was 50:50.On the basis of the 50:50 ratio of BG to β-TCP,the effect of the introduction of WG and γ-PGA on the properties of BG/β-TCP bone cement was investigated,and the results showed that the introduction of WG and y-PGA greatly improved the anti-collapse ability of the bone cement,when βTCP:BG:WG was 45:45:10 and 10 wt%γ-PGA was used as the reaction fluid The injectability of the bone cement was increased from 11%to 96%.Compared to the mechanical compressive strength of the unmodified BG/β-TCP-based bone cement,the mechanical compressive strength of the bone cement with the introduction of 10 wt%WG and the use of 10 wt%yPGA as the curing reaction fluid increased from 8.83 ± 0.98 MPa to 53.03 ± 4.12 MPa.In vitro cell culture experiments confirmed that the prepared β-TCP composite bone cement samples were all bio compatibility.（3）Preparation of CSH-doped BG-modified β-TCP bone cement and study of its mechanical properties in bone modelsIn order to further improve the degradation properties of the above bone cements,the introduction of CSH,which degrades at a faster rate,was used in this section to investigate the effect of its content on the properties of the bone cements and finally to compare them with PMMA bone cements,which are currently widely used in clinical practice,in an in vitro bone model repair experiment to investigate their potential application as vertebral reinforcing agents.The results showed that the operability of the bone cement decreased slightly with increasing CSH introduction,mainly in terms of injectability.However,the degradation rate of the bone cement was greatly improved,increasing from 5.88%to 14.21%after 21 days of degradation with the addition of 25 wt%CSH.In vitro bioactivity and biocompatibility experiments showed that the introduction of appropriate CSH had no effect on the bioactivity and cytotoxicity of the bone cement.Finally,a comparison with commercial PMMA bone cements in terms of bone repair properties showed that CSH/CPC bound better to bone tissue with an adhesion strength of 138±7.53 N.In the comparison of bone repair capacity,the compressive load after repair was higher for commercial bone cements at 8107.33±551.62 N.