The Experimental Study Of Repairing Cranial Defect With The 3D Printed Customized Hydroxyapatite (HA) Prosthesis

BackgroundsExtensive cranial defects caused by various causes such as trauma,infection,congenital malformation and iatrogenic injury will not only seriously affect the appearance of patients,but also lead to serious complications such as cerebral cortical hernia,subdural effusion,seizures and trigeminal syndrome.Therefore,cranioplasty is of great significance for achieving the anatomical reconstruction of skull,brain protection,aesthetic recovery,neurophysiological improvement and prevention of severe complications.Cranial repair materials commonly used in clinical practice currently include autogenous bone,allogeneic bone,and artificial materials.Among them,autogenous bone not only causes secondary trauma,but also has very limited bone sources.The allogeneic bone has the risk of infection,and it is very difficult to shape.Therefore,it is of great clinical significance to explore alternatives suitable for repairing cranial defects.The traditional alternative materials for artificial cranial repair mainly include bone cement,plexiglass,polymer fiber reinforced materials,silicone rubber plates,titanium,polymethyl methacrylate(PMMA),polyether-ether-ketone(PEEK),and high-density porous polyethylene.However,these materials are very different from the composition of human bone tissue,and their tissue compatibility is relatively low.Hydroxyapatite,as the inorganic substance with the highest content in human bone tissue,has no doubt about its biocompatibility,bone conductivity and osteoinductivity.However,the characteristics of HA material such as high brittleness,high hardness and difficulty in processing make it difficult for HA to carry out clinical transformation in repairing cranial defects.Through 3D printing technology,various prostheses with complex structures can be personalized printed,so that the prosthesis can accurately repair cranial defects.Therefore,it is of great significance to explore the biosafety,biocompatibility,mechanical properties,osteogenic properties and biomechanical properties of 3D printed HA prosthesis used for human cranial defects,so as to explore the clinical transformation of 3D printed HA prosthesis used for repairing cranial defects.Purposes1.To study the cytotoxicity of the 3D printed HA cranial repair prosthesis material and the ability of the prosthesis to repair rabbit skull defects,and to evaluate the biosecurity,biocompatibility and osteoinductive properties of the 3D printed HA cranial repair prosthesis.2.Analyze the stress and strain of the 3D printed personalized HA skull repair prosthesis when subjected to external forces,and explore the biomechanical properties of the 3D printed personalized HA skull repair prosthesis to provide the necessary experimental basis for clinical application.Methods1.The cytotoxicity experiment:the CCK-8(Cell Counting Kit-8)method was used to detect the effect of the extract of 3D printed HA rabbit skull repair prosthesis(experimental group)on cell proliferation.In this experiment,a positive control group(6.5%phenol solution),a negative control group(high-density polyethylene extract)and a blank control group(complete medium)were simultaneously set for control observation.2.Prosthesis implantation experiment:3D printed HA cranial repair prosthesis was used to repair skull defects in 12 rabbits.The effects of 3D printed HA prosthesis on repairing rabbit skull defects were evaluated by gross observation and imaging.3.Three-dimensional finite element analysis:the skull CT data of one patient with cranial defect was preliminarily processed and a three-dimensional model of the cranial defect was constructed,and then 4 kinds of 3D printed personalized HA cranial prosthesis models with different thicknesses were designed by reverse engineering software.Finally,the stress and strain of different thickness 3D printed personalized HA cranial prosthesis when subjected to different forces are analyzed by three-dimensional finite element analysis.Results1.The cytotoxicity experiment:the Optical Density(OD)of the experimental group was 2.9975 after CCK-8 solution was added for 4 hours,at which time the Relative growth rate(RGR)was 101.94,and the cytotoxicity level of HA was 0 level.2.Prosthesis implantation experiment:through general observation,it can be seen that the prosthesis is closely combined with the cranial,the prosthesis structure is relatively stable,and there is no obvious looseness or displacement.No obvious rejection and inflammatory reaction occurred in the implanted area.The imaging results showed that the bone tissue around the prosthesis healed well,some new bone was formed in the pores inside the prosthesis at the edge of cranial defect,and the prosthesis formed a good osseous bond with the surrounding bone tissue.3.Three-dimensional finite element analysis:through reverse engineering method and three-dimensional finite element method,4 kinds of 3D printed personalized HA cranial prosthesis three-dimensional finite element models with different thicknesses were successfully established.Those models have good geometric similarity and biomechanics similarity.At the same time,the results of finite element analysis show that when the prosthesis is subjected to concentrated forces in the central area of the same size and direction,as the thickness of the prosthesis increases,the maximum equivalent stress and maximum strain experienced by the prosthesis show a downward trend.In addition,the maximum equivalent stress value of the prostheses of different thicknesses under the action of the set concentrated forces of different magnitudes is less than the limit stress value of the HA material.In addition,when the thickness of the prosthesis is constant,the stress and strain of the prosthesis gradually increase with the increase of the applied force.Conclusions:1.The 3D printed HA cranial repair prosthesis has good biosafety and biocompatibility.The pore structure on the surface of the prosthesis can induce new bone formation to a certain extent,indicating that HA has good bone-binding properties and osteoinductive properties.2.The 3D printed personalized HA cranial repair prosthesis has stable structure and good biomechanical properties.The mechanical strength when its thickness exceeds 2mm can basically meet the general mechanical needs.