Experimental Study On CNTs/HA/PDLLA Biodegradable Intervertebral Fusion Cage

BackgroundsSince the proposed introduction of the stainless steel basket as an adjunet to human spinal arthrodesis,great change occured in inter-vertebral fusion history. Although the effect of cage to treat spinal disoder is very good,but some pitfalls have been founded about cage in long term follow-up.The research on cage have not been stop,so numerous types of cage devices have been designed,specially the use of those cage devices for lumbar intervertebral fusion has been rapidly popularized wordwide Posterior lumbar intervertebral fusion(PLIF) was introduced to clinical practice in the mid-1940s by Jaslow and Cloward.Cage technology has profoundly changed the approach to spinal fusion,great success has been achieved in treatment of spinal disorder and injuries.and then there has been a resurgence of intrest in performing interbody fusion.There are many kinds of cage,According to the shape of cage,it can be divided into cylindrical or conical cages;Box-shaped or rectangular cages.According to the materials of cage,there are two kinds of cages no-absorbable cage such as metal cage,absorbable cage.But their have the same aim to provide mechnical stability for spine and restore disc height.Early reports on interbody cages are mainly positive,but with longer follow-up,the number of complications reported is increasing,Most of these complications are inherent to the fact that the cages are non-degradable,especially when made of metal.First,there is a remarkable mismatch between the mechanical properties of metals and bone.High stiffness decreases graft loading within the cage,a condition calling stress shielding.A metal implant thus slows down the fusion process,eventually resulting in pseudarthrosis,corrosion, wear,and ultimately migration A second disadvantage of metal implants is that they are radiopaque and thus eclipse the fusion zone during radiological evaluations. Bioresorbable cages,on the contrary,their stiffness is comparable to that of bone, they are radiolucent,and they resorbable over time.Bioresorbables,however,have their own drawbacks and pitfalls.First,their strength is usually considerably lower than that of metals or non-degradable polymers,Specially when they were implanted in the body of man or animal,degradation would weaken it's mechanical which is just enough to meet the demand of lumbar.Research demonstrate that the PDLLA can not stand the load of the spine after 4 weeks post-operation,when the spine have not healing and need stability,therefore to enhance their initiate mechanical force and to sloe down the degradation rat of PDLLA become the key roleObjectivesIn order to tackle the problem of the PDLLA(poly-DL-lactic Acid) cage lack of enough strength to support the spinal axial compression.This study is try to develop CNTs/HA/PDLLA degradation cage,and put it into experiment to observe its property,such as biomechanical,and its influence on the fusion process and its transformation during degrading period in vivo.Methods1.Consulting relative domestic and overseas literatures in recent yeas,then to design the strengthen degradable cage which mad from carbon nano-tube(CNTs),Hydroxyapatite(HA),PDLLA(poly-DL-lactic Acid),this three kinds of material formed composite have good interface so that CNTs/HA/PDLLA cage mechanical have been enforced;2.According to the standard of ISO10993-1,the biocompatibility of CNTs/HA/PDLLA was evaluated both in vitro and in vivo including cytetoxicity test, NCTC L929 cells were selected to incubated with PDLA,CNTs/HA/PDLLA,and DMEM.To explore the biocompatibility of CNTs/HA/PDLLA composite,implant test were performed in SD rat3.Cages was put on computer-contrlled material machine to measure the initial maxium compression strength of PDLLA and CNTs/HA/PDLLA cage,each groups consist of 10 cage.4.To evaluate effect of the CNTs/HA/PDLA cage in the unstable lumbar spinal function unit(SFU),eight goat SFU of L3-4 were applied,after discectomy,iliac crest,carbon fiber cage,CNTs/HA/PDLLA cage were inserted respectively,to comprise multidirectional flexibility among normal group unstable group,iliac crest group,carbon fiber cage group and CNTs/HA/PDLLA cage group,after that maxium pull-force of each cage and iliac crest were test.Data of experiment were recorded.5.To observe thee effect of CNTs/HA/PDLLA cage in vivo,lumbar fusion was underwent on 18 female goat,six of them were implanted with iliac crest,six of them applied with PDLLA cage,and the others were treated with CNTs/HA/PDLLA cage. Disc height vary were recorded at after operation,4,12,24week post-operation by radiological assessment and vertebra fusion were evaluatedresults1.CNTs/HA/PDLLA cage was mad with CNTs HA and PDLLA,the molecular weight of 80 million,by injected model,it can provide 1.3cm~3 space for autograft, the interface of autograft and endplate is 1.18cm~2,all of them larger than carbon fiber cage's.2.The L929 cells incubated with CNTs/HA/PDLA and PDLA group both grew well. With relative growth rate over 95%.The cytotoxicity of CNTs/HA/PDLLA and PDLA were under gradeⅠaccording to the ISO10993-1 standard.For biocompatibility in vivo with SD rats,ICI of gradeⅣoccurred in the muscular tissues around the CNTs/HA/PDLLA and PDLLA implant 1 week after operation without formation of complete capsule,and at 4 week,ICI was lowered to grade 1 with grade 4 capsular reaction.Till week 12,the ICI and capsular reaction were both first grade.3.The maxium initial compressure force of CNTs/HA/PDLA cage was 7.453±0.555KN,compare with PDLLA cage which maxium initial compressure force was 6.004±0.368KN,there was statistical difference.It was obviously that CNTs/HA/PDLL A cage owned stronger initial mechanical than PDLLA cage.4.Wathever CNTs/HA/PDLA cage and carbon fibber cage could significantly decrease the ROM of unstable spine at flexion,extension and lateral bending,when their were inserted into goat lumbar L3-4,which discectomy were underwent,there were no significant difference between CNTs/HA/PDLLA cage and carbon fibber cage(P＞0.05);when compare with iliac crest group,the two kinds of cage could enhance the stability of discectomy spine.The maximum pull-out force of iliac crest group,CNTs/HA/PDLLA cage group and carbon fiber cage group were 152.750±22,253KN,295.575±30.125KN,304.038±32.244KN,there were significant difference when iliac group compare with carbon fiber cage and CNTs/HA/PDLLA cage respectively(P＜0.05),There were no significant difference between CNTs/HA/PDLLA cage and carbon cage(P＞0.05),but showed difference when they compared with iliac groups(P＜0.001).5.CNTs/HA/PDLLA cage own good mechanical property whatever in vitro or in vivo, it's mechanical decent slowly than PDLLA when it were implanted in body,so CNTs/HA/PDLLA cage could maintain disc height after operation,but PDLLA cage degrade rapidly after their implanted in goat,so it loss their mechanical force quickly, therefore disc height loss more obviously than CNTs/HA/PDLLA group,at 4,12, 24 week the loss disc height of the PDLLA group were -0.556±0.296mm,-0.817±0.471 mm,-0.074±0.030 mm respectively,and CNTs/HA/PDLLA group's loss disc height were -0.441±0.233mm,-0.285±0.151 mm,-0.078±0.067mm at 4,12, 24 week pot-operation.When CNTs/HA/PDLLA group'loss disc height compared with PDLLA group's,there was statistical difference(P＜0.005).But two kinds of cage could facilitate veterbrate fusion.Conclusions1.CNTs/HA/PDLLA cage could provid more large space and more large surface for graft than carbon fiber cage under the condition of same volume,benefit for verterbra fusion.2.CNTs/HA/PDLLA owne good biocompatibility and without cytotoxicity,meet the demand of ISO10993-1,therefore CNTs/HA/PDLLA cage could be implanted in body of people.3.CNTs/HA/PDLA cage owned more strong initial mechanical than PDLA cage, meet the demand of spinal loading.4.CNTs/HA/PDLA cage could recovered of stable spinal which become unstable after discectomy.5.CNTs/HA/PDLA cage had good mechanical in the body of goat until the verterbral fusion,and could prenvent from loss disc height.To sum up,CNTs/HA/PDLLA cage own good biocompatibility and enough mechanical strength to guarantee operation segment stable until fusion,in the same time it can facilitate veterbrate fusion enhance fusion rate,so CNTs/HA/PDLLA cage is promising.