| BackgroundDisc degeneration and disc herniation are the main pathological entitles to date in patients with common back pain. Although many discetomy operations can achieve good short-term results because of the decompression of the nerve system, the lost of the load sharing capacity of intervertebaral disc will produce much biomechanical disturbance. In the long term after operation, hypertrophy of the facet joints, stenosis of the spinal canal and the instability of lumbar spine will come forth inevitably. Spinal arthrodesis can completely resect the degenerative disc and stabilize the affected motion segment, however after fusion the increased stress will transfer to the adjacent segment, which will promote degeneration and start the vicious cycle again. Furthermore, the spinal arthrodesis will produce many complications, such as iliac donor site morbidity, failure of the fusion and pseudoarthrosis. Lumbar nucleus artificial replacement technique in the treatment of lumbar degenerative disease due to preserving motor function, in theory, be able to overcome the shortcomings occurred in the simple lumbar discectomy or lumbar fusion. In recent years, domestic and foreign scholars pay many attentions to this technique research, and reported the excellent short-term follow-up results. But with the extension of follow-up, there were some complications, such as end-plate cartilage injury and prosthesis subsidence. Some authors thought these may be related to high elastic modulus of nucleus prosthesis.In order to explore a better nucleus biomaterial, we research group developed a new type of artificial nucleus materials --- Pectin/PVA composite (CoPP) hydrogel. Through the study of the mechanical properties, swelling properties and other related items of the material found that CoPP hydrogel is a kind of viscoelastic material, which is softer and more tenacious, has better absorption shock of load, whose elastic modulus is near to the optimal elastic modulus of preformed prosthetic nucleus pulposus, has better permeability of substance in contrast to PVA hydrogel, and is suitable to made preformed prosthesis of lumbar nucleus pulposus.The elastic mode of CoPP hydrogel is about 2.8Mpa, is expected to become the ideal artificial disc nucleus material.This study continues to finish its tissue biocompatibility after its basic research. To evaluate its biomechanical properties after implanting it in the human lumbar cadaveric specimens; And to set up the surgical model of lumbar nucleus replacement in rabbit, and compare the antidegenarative effect of pectin/PVA hydrogel and polyvinyl alcohol hydrogel as a nucleus Prosthetic.Objective1. To evaluate the biocompatibility of pectin/polyvinyl alcohol composite (CoPP) hydrogel as a new kind of prosthetic nucleus.2. To evaluate the kinematic changes at the operated segment and above adjacent segment and the intradiscal pressures at above adjacent segment following anterior insertion of pectin/polyvinyl alcohol composite (CoPP) hydrogel and cage. 3. To evaluate the antidegenerative effect of pectin/ polyvinyl alcohol composite (CoPP) hydrogel as artificial nucleus material in an animal surgical model.Methods1. According to China national standard GB/ T16886 documents, the toxicity of CoPP prosthetic nucleus material was invested by the acute toxic test, sensitization test, hemolysis test, Ames test, mice marrow micronucleus test and chromosome aberration test of mammalian cell in vitro.2. Six cadaveric lumbar spine specimens (L3～L5) were used for biomechanical testing. Extraneous soft tissues were removed, leaving facet capsules, intervertebral discs, and ligamentous structures intact. The biomechanics test used a robotics-based spine testing system. The specimen was fixed within the testing system using surgical pedicle screws. L4/5 was the operated disc. Kinematics at L3/4 and L4/5 were determined using displacement control. The loading angle as follows, flexion was 20°, the other five motion direction was 15°. The loading rate was 1°/second. Intradiscal pressure at the above adjacent segment (L3/4) was measured using Samba pressure sensor. The spines were tested initially intact and following CoPP and cage insertion. Specimens were sequentially loaded three times, with data collected during the final loading cycle to ensure intraspecimen repeatability. Intradiscal pressure and segmental motion measurements were recorded at a frequency of 0.5 kHz during fexion/entension, lateral bending and axial rotation motions on intact specimens and after anterior lumbar CoPP implanting or cage implanting at L4/5. Measurements of maximum fexion/entension, lateral bending and axial rotation motions were used to calculate the changes in intradiscal pressure and segmental motion under different states, and were statistically analyzed using SPSS software. 3. Forty-eight Nealand white rabbits were underwent animal model, the L4/5 or L3/4 intervertebral discs were pierced with a Gauge#16 needle and polyvinyl alcohol (PVA) or CoPP implants were inserted into the holes. For comparative purposes, the other discs(L3/4 or L4/5) underwent sham treatments or control treatments in which the disc was pierced but no implant was inserted. All the discs were devided four groups as follows:sham disc group, stab disc group, PVA disc group and CoPP disc group. The discs were analyzed radiologically and histologically for degenerative changes at 1,3, or 6 months after surgery.Results1. After leaching liquor or saline injection 72h, the body weight of mice in CoPP group and negative control group showed an increasing trend. The two group mice had no diarrhea, convulsions or other abnormal behavior, no mortality. Positive control mice after injection of phenol, all died immediately. The body temperature of the first three testing rabbits were 0.3,0,-0.1℃after injection of CoPP material extract, the total rising temperature was 0.2℃in the three rabbits together. So the CoPP material showed no acute toxicity and pyrogenic. In the sensitization test, after leaching liquor or saline injection, no cutaneous reaction occurred such as erythema or edema. In the positive group, however, there were midrange reactions in four mice and severe reactions in six mice. This result confirmed that the CoPP material did not induce sensitization. A reverse mutation test with Salmonella typhimurium showed that no significant effect on the number of histidine revertants of TA97, TA98, TA100 and TA102 strains after CoPP was added. The micronucleus rate was less than 5% in bone marrow cells; there was no significant difference compared with the negative control group (P> 0.05). The rate of chromosome aberration was less than 5%; no significant difference was found between the CoPP culture and the control groups. 2. (1)Kinematics:At the implanted level (L4/5), the CoPP spine showed a nonsignificant change in the other five motion direction except left lateral bending motion compared with the intact spine (P>0.05), whereas the cage spine decreased significantly in all motion direction when compared with the intact spine(P<0.05). Not only did cage spine reduce relative to the intact spine, but also reduced significantly relative to theCoPP spine. At the above adjacent level of L3/4, the CoPP revealed a minor change in all motion direction except left lateral bending motion compared with the intact spine (p>0.05), whereas the ROM of cage spine significantly increased in all motion direction when compared with the intact spine (P<0.05). (2) Intradiscal pressure (IDP) at L3/4 leval:IDP was only measured at the rostral adjacent level. The IDP did not increased in any condition with the presence of CoPP impant compared with intact spine (P> 0.05). While after the cage implantation, the IDP was signifcantly increased in flexion/entension and left/right lateral bending relative to the intact spine (P< 0.05), but there was no significant increasing in axial rotation relative to intact spine (P>0.05). (3) Anterior disc height(ADH):After nucleuectomy, in the absence of load conditions, the disc height decreased by 12.5% relative to intact state; after loading 500N, disc height decreased by 15.7% relative to intact state, the differences was significant between the nucleuectomy spine and intact spine before or after loading (P<0.05). However, once CoPP implanted, no load conditions, the disc height increased 0.87% compared with intact spine; after loading 500N, disc height increase by 6.6% relative to intact state, and there was no significant difference between CoPP spine and intact (P>0.05). But the ADH of the CoPP spine were higher than that of the nucleuectomy group by 13.3%, 24.5% before and after loading respectively, and the difference was significantly (P<0.05). It indicated CoPP implantation could maintain intervertebral disc height after removal of nucleus.3. It was easy to expose the lumbar spine of the rabbit through left antero-lateral extraperitoneal surgical approach. In this approach, we coud reveal L2-L6 vertebral body well and the left antero-lateral part of the most intervertebral disc. There was no much blood loss, no peritoneal tearing during the operative procedures.In this study,3 of 48 rabbits died before havesting. One rabbit died due to overdose anesthesia; one died after 3 days, Lossing much blood was related to the death. The other one died in 3 weeks because of its secondary urinary tract infection after right lower limb paralysis. The remaining 45 rabbits were all alive before havesting. Macroscopically, none of the implants showed any signs of displacement at the time of harvest. CoPP or PVA implants were firmly fixed to the disc and not easily pulled out from the disc after 3 months postoperatively. The local around CoPP or PVA implants was similar to the sham disc, no color anomalies or inflammatory response. While the osteophyte occurred in the stab disc after 3 months postoperatively. Radiologic analyse showed the %DHIs of the CoPP, PVA discs and the sham discs were significantly greater than those of the stab discs at any time (P<0.05). The %DHI of the sham disc at 1,3 and 6 month postoperatively was (90.6±1.13)%,(90.1±0.37)%,(81.7±20.3)% respectively; The %DHI of the stab disc at 1,3 and 6 month postoperatively was (69.3±5.8)%,(63.4±0.81)％,(55.1±7.1)% respectively; The %DHI of the PVA disc at 1,3 and 6 month postoperatively was (93.3±2.6)%,(89.9±0.14)％,(76.6±4.8)% respectively; The %DHI of the CoPP disc at 1,3 and 6 month postoperatively was (94.7±2.6)%,(91.3±1.9)%,(77.6±19.3)% respectively. The %DHI of the CoPP discs or PVA discs decreased slightly over time. There were no significant differences between CoPP discs, PVA discs and sham discs at 1,3 and 6 month postoperatively (P>0.05). There was a litte clearance between the CoPP or PVA implants and the intervertebral disc at 1 month postoperatively, but with time increasing, the clearance was not clear and disappeared finally. All implants got mid flattening in the craniocaudal direction and touched the endplates tightly at 6 months postoperatively, There were 3 PVA implants subsided into the endplate, while only 1 CoPP implant subsided into the endplate at 6 months postoperatively. Disorganization of the lamellae was confined in the inner one third of the AF at 1 month postoperatively, but gradually spread to the middle one third of the AF thereafter. The NP space of the CoPP or PVA disc was mostly occupied by the implants, and severely reversed lamellae of the AF were not observed. But the severely reversed lamellae were larger and more common in the stab discs. The grade of degeneration of the CoPP or PVA discs and sham discs was significantly lower than that of the stab discs throughout the period (P <0.05). There were no significant differences between CoPP discs, PVA discs and sham discs at 1,3 month postoperatively (P>0.05), but at 6 month postoperatively, differences between the grade of degeneration of CoPP or PVA discs and that of the sham discs were significant(P<0.05).Conclusion1. The CoPP hydrogel has good biocompatibility and can potentially be used as an implant material.2. The CoPP prosthetic nucleus not only preserves the motion function of the operated leval but also maintains the motion and intradiscal pressure at adjacent level compared with lumbar cage group. The new CoPP prostheses can restore the stability and height of the intervertebral disc after nucleotomy.3. The antidegenerative effects of CoPP prosthetic nucleus replacement surgery were demonstrated by quantitative radiologic and histologic analyses. Degeneration of the anulus fibrosus after the replacement treatment was delayed by preserving disc height and occupying the space of the nucleus pulposus. Properly designed implants and minimally invasive techniques are necessary for long-term success.
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