Development And Preparation Of A Novel Calcium Phosphate-based Nanocomposite And Its Application In Augmenting Cannulated Pedicle-screw Fixation

Polymethyl methacrylate(PMMA)has been widely used for the augmentation cannulated screws fixation and has been shown good enhancement in clinical applications.However,PMMA also has many drawbacks such as toxicity of monomer,high stiffness,lack of osteoconductivity and its non-degradability in vivo.In order to solve the above problems,starch and developer barium sulfate were added to calcium phosphate cement(CPC),and prepared a novel injectable,biodegradable calcium phosphate nanocomposite(CPN)in the present study.This study focused on the characterization and analysis of the structure and properties of CPN,and explored the reinforce effects and potential application in cannulated pedicle screw fixation.In the first part of this study,the CPC was improvement.Starch and developer barium sulfate were added and a novel injectable,biodegradable calcium phosphate nanocomposite(CPN)was developed,and characterization of CPN by means of apparent morphology and mechanical testing was carried out.In addition,to meet the clinical requirements for screw-augmented,this study also studied the injectability,biocompatibility and in vivo osseointegration of CPN.Compared with the traditional CPC,the anti-collapse and mechanical properties of CPN were significantly improved,and the compressive strength of CPN was about 50 MPa,which is more than three times than CPC(13.21±2.45 MPa),and its compressive modulus was also significantly improved(1.01±0.29 GPa).CPN also showed similar injection properties compared with PMMA,and the injection rate could reach 95±1%when the mixed molding liquid-solid ratio(L/S)of CPN was 0.6 mL/g.In addition,CPN showed faster self-setting characteristics,its initial solidification time and final solidification time were all shorter than PMMA,indicating that the operating time of CPN was suitable for the clinical application.The biocompatibility of CPN was measured by a CCK-8 cell proliferation-toxicity assay kit.The results showed that the cellular proliferation of the CPN was higher than that of PMMA,and the relative cell proliferation rates were 1886%and 1277%after 3days(p=0.018).To further evaluate the biodegradation of CPN,a rabbit model of femoral bone defect was used to assess the biodegradation and osseointegration behavior of CPN up to 24 weeks.The results showed that new bone tissue occupied the vacancy due to CPN resorption and formed a tight contact with the existing cement,suggesting a typical degradation and new bone ingrowth into CPN samples.The above results indicated that CPN has shown good biological properties.In the second part of this study,the fluidity and dispersing properties of CPN in the ASTM standard open-cell foam model(Sawbones,model 1522-507),decalcified sheep vertebra model and human osteoporotic lumbar vertebrae were evaluated compared to PMMA.The projection areas and dispersing volumes of the open-cell foam blocks were calculated.In the lumbar vertebra,the screw was accurately placed under the guidance of the 3D printed template and the bone cement was injected into the vertebra.A-P and axial view of X-ray films of each single vertebral body was performed and the projection area was measured to evaluate the dispersion properties of the bone cements,and three-dimensional CT reconstruction was performed on the augmented lumbar samples in order to measure the dispersive volume of the different bone cements.Results in the three models showed that CPN has similar interdigitation ability to PMMA;CPN diffused and interdigited into a sponge-like bone structure in the open-cell blocks;In the sheep vertebra,CPN showed good fluidity and could cross and diffuse in the porous bone structure;CPN could reach the distal hole of the screw in human osteoporotic lumbar vertebrae,which was suitable for the clinical application.In the final part of this study,the reinforcing effect of screws augmentation with cements was studied.The biomechanical properties of CPN in the solid foam and open-cell foam models,decalcified sheep vertebra model and human osteoporotic lumbar vertebrae were evaluated compared to clinical PMMA.The results in the open-cell foam model showed that CPN has better anti-pullout ability than clinically used PMMA.The CPN-augmented cannulated screw reached the highest force of 121±6 N,which was higher than that of PMMA(100±23 N)and CPC(98±6 N).In vitro evaluation in decalcified sheep vertebral models showed that the axial pullout forces of CPN(1351±324 N)and PMMA(1459±304 N)were similar,there was no statistical difference(p=0.35).The results in the cadaver vertebrae further confirmed that CPN(1199 ± 225 N)and PMMA(1337±483 N)have similar reinforcing effects,although the mean value of CPN was slightly lower,there was no statistical difference(p=0.47).The excellent anti-pullout property of CPN clearly suggests its potential for replacing PMMA in the application of cannulated pedicle-screw fixation.