Topology Optimization Design And Performance Research Of Cervical Zero-profile Cage Based On Additive Manufacturing Technology

BackgroundCervical spondylosis is a series of syndromes involving neck and shoulder pain,numbness and weakness of the limbs triggered by degenerative changes in the intervertebral discs and their secondary degeneration of adjacent tissue structures,which further irritate or compress the spinal cord,nerve roots,and other tissues.The prevalence of cervical spondylosis in China is about 13.76%,among which the incidence of cervical spondylosis in people over 45 years old is 19.03%,and the incidence of cervical spondylosis in women is higher than that in men(16.51%vs.10.49%).Cervical spondylosis is usually accompanied by neurological symptoms such as numbness and weakness in the limbs and unsteady walking,which can significantly reduce the patients’ quality of life.For patients with significant neuromotor impairment,surgery is a better treatment option.Anterior cervical fusion and posterior cervical fusion are commonly performed for the treatment of cervical spondylosis,and previous studies have shown that anterior cervical spine surgery has a lower complication rate(7.8%vs.20.3%).The current consensus suggests that anterior cervical discectomy fusion is the standard operation for the treatment of cervical spondylosis.However,postoperative complications related to internal fixation devices,such as adjacent segment degeneration,cage subsidence,and dysphagia,have always been a painful problem in the clinical treatment of cervical spondylosis.Previous literature has reported that the reasons for the related complications include excessive elastic modulus of the internal fixation device,which does not match the elastic modulus of the cervical bone;poor fit to the cervical spine,which leads to uneven stress transfer and distribution;and limitations in the design of the form-fitting structure.Additive manufacturing,also known as 3D printing,is a production process of rapid prototyping technology.It is a process that utilizes the concept of "discrete and stacking" based on a digital model design,whereby materials such as photosensitive resins or metal powders are molded layer-by-layer to achieve free-form molding of parts.Topology optimization is the process of re-optimizing the structure and material distribution within a pre-determined geometric design area,to maximize the comprehensive performance of the model.In recent years,with the continuous development of additive manufacturing and topology optimization,the two technologies have been gradually applied to the medical field,especially in the field of orthopedic implant design.To address the above clinical problems,this study introduces additive manufacturing and topology optimization technologies into the investigation and development of cervical cage.Purpose and SignificanceThe research aims to design a novel individualized zero-profile cage(NIZP Cage)based on additive manufacturing technology.The biomechanical properties of the NIZP Cage were evaluated using finite element analysis.Combined with biomechanical and in vitro cellular experimental methods,topology optimization techniques were applied to the structural design and material optimization of the cage to reduce the equivalent elastic modulus,improve its mechanical properties,and enhance its ability to induce bone growth in order to reduce the risk of complications associated with internal fixation devices after cervical spine surgery.At the same time,a complete set of new methods for design,optimization,and performance verification of customized devices is established,which provides a theoretical basis and reference for the future orthopedic individualized device design and clinical treatment.MethodsThe whole cervical spine thin-scan CT data of a volunteer was recruited and collected.A set of C3-C7 non-homogeneous finite element simulation model was reconstructed by reverse engineering,and the validity of the model was verified.Based on the anatomical characteristics of C5/6,a NIZP Cage was designed using Materialise 3-matic,Materialise Magics,etc.Meanwhile,finite element analysis software,such as Hypermesh,ABAQUS,etc.,was used to simulate the anterior cervical discectomy and interbody fusion surgery,and the NIZP Cage and Cage and Plate Constructs(CPCs)were implanted during the operation,respectively.Finite element analysis was used to evaluate the advantages and limitations of the mechanical properties of NIZP Cage.In order to further improve the comprehensive performance of the NIZP Cage,four kinds of porous scaffolds with different lattice units were designed and printed.Finite element analysis and in vitro mechanical experiments were used to evaluate the mechanical properties of each porous scaffold,such as stress conduction and distribution,elastic modulus,yield strength,etc.In addition,in vitro cellular experiments,such as cell proliferation,live-dead staining,alizarin red staining,and alkaline phosphatase activity test,were used to evaluate the biological properties of each porous scaffold,so as to screen out lattice units that balance the advantages of both biomechanical and biological properties.Based on these results,the topology optimized novel individualized zeroprofile cage(TO NIZP)was re-designed and reprinted by using topology optimization techniques,and the stresses,conductivity and distribution,compressive resistance and stiffness of the TO NIZP before and after optimization were compared and evaluated by using finite element simulations and in vitro mechanical experiments.Finally,the mechanical properties of TO NIZP,such as stress conduction and distribution,compressive resistance,etc.,were evaluated using finite element simulations and in vitro mechanical experiments.Results(1)After mesh sensitivity analysis and validation,0.8 mm was determined as the optimal mesh size for the C3-C7 non-homogeneous finite element model,and it was confirmed that the model could reflect the biomechanical properties of the cervical spine well.(2)In the finite element experiments,the intervertebral mobility of the surgical segments was reduced by more than 95%under all motion conditions,indicating that the NIZP Cage can effectively limit the mobility of the surgical segments and provide immediate postoperative stability.The peak stress of the NIZP Cage was reduced by 30.01±8.3 MPa compared with that of the CPCs group,while that of the titanium plates or screws increased by 129.5±94.4 MPa.Compared with the CPCs group,the lower surface of C5 and the upper surface of C6 in the NIZP group showed a clear and uniform stress distribution profile,and the stress concentration area was smaller.(3)The details of the entities printed by selective laser melting technology are accurate and the structural features are clear,and no obvious cracks,holes,or other structural defects are found.In the in vitro mechanical experiments,the true modulus of elasticity of Octet,Body centered cubic(BCC),Face centered cubic(FCC),Bionicbone surface(BBS)porous scaffolds are 3672.78±117.07 MPa,2356.97±64.13 MPa,3942.64±141.35 MPa,and 4176.81±186.23 MPa,respectively.And the true yield strengths were 162.61±4.20 MPa,88.14±9.49 MPa,168.16±1.97 MPa,and 184.70±6.77 MPa,respectively.The cell proliferation in CCK-8 cell proliferation experiments was significantly higher than that of the BBS scaffolds at day 3.In the CCK-8 cell proliferation assay,the cell proliferation in BCC,BBS and Octet scaffolds was significantly higher than that in FCC scaffolds on day 3(P<0.001),and that in BCC and BBS scaffolds was significantly higher than that in the other two groups on day 5(P<0.001 and P<0.0001,respectively).In the live-dead staining assay,on day 3,it could be seen that there was an obvious increase in the number of adherent and aggregated live cells on the surface of the porous scaffolds in the various groups and the sparse sieve mesh had become denser.On day 5,it could be seen that a large number of viable cells had adhered to the surface and interior of porous scaffolds of each group,and obvious cell stacking and aggregation phenomenon had occurred.In alizarin red staining and semi-quantitative analysis,there was no significant difference in the number of calcium nodules among the scaffolds at day 7,and the BCC scaffolds and BBS scaffolds had the best osteogenic differentiation ability at day 14(P<0.01).In alkaline phosphatase activity assay and semi-quantitative analysis,there was no significant difference in the osteoclast activity among the scaffolds at day 7,and the BCC scaffolds had the better osteoclast activity at day 14(P<0.01,P<0.01 and P<0.01,respectively).(4)In the finite element experiment,compared with the NIZP group,the peak stress of the TO NIZP fusion device was reduced by 52.5±17.1 MPa,and the peak stress of the screws was reduced by 25.0±5.8 MPa;compared with the NIZP group,the stress distribution profile of the lower surface of the C5 and the upper surface of the C6 in the TO NIZP group was clearer and more uniform,and there were fewer stress concentrations;and in the in vitro mechanic experiment,the TO NIZP fused with a structural structure.In the in vitro mechanical experiments,the pressure endured by TO NIZP when structural damage occurred was 7559 N.Conclusions(1)NIZP Cage can effectively rebuild the stability of spinal structure after cervical fusion surgery and shows superior mechanical properties,but the solid structure does not have the function of promoting osteoblasts to grow in,and further optimization of the design is still needed.(2)The BBS porous scaffold has the best comprehensive biomechanical and biological properties,while the BCC porous scaffold has the lowest modulus of elasticity and excellent biological properties.(3)The TO NIZP has lower peak fusion and screw stresses and more uniform stress distribution under various motion conditions.The implantation of TO NIZP does not further increase the risk of disc degeneration in the adjacent segments,and optimizes stress transfer and distribution in the adjacent vertebrae,thereby reducing the risk of stress shielding.In addition,the TO NIZP has a personalized zero profile,which can reduce the irritation and damage to the surrounding tissues and organs,and reduce the risk of postoperative dysphagia.