颈椎椎间融合器融合效果的在体动物研究

目的在活体山羊颈椎上比较三面皮质自体骨、垂直圆柱体Harmscage及方盒形Carboncage的椎间融合效果。方法取24只成年雄性山羊,随机分为三组:自体骨组、Harmscage组及Car-boncage组。所有动物均行C3-4椎间盘切除术并分别植入以上内植物。于术前、术后即刻及术后1、2、4、8、12周摄颈椎正侧位X线片,于侧位X线片上测量平均椎间高度、椎间角及前凸角;术后12周处死动物,取C3,4节段标本进行组织学评估。结果术后1周Carboncage组的平均椎间高度、椎间角及前凸角大于Harmscage组和自体骨组(P<0.05);术后12周两个cage组的平均椎间高度、椎间角及前凸角均大于自体骨组,差异有统计学意义(P<0.05)。术后12周依据融合分级标准对三组进行影像学评估,和自体骨组比较,两个cage组的骨融合效果略好,但无统计学意义;组织形态学亦发现两个cage组的椎间融合效果较好,但与自体骨组比较差异无统计学意义。垂直圆柱体Harmscage中形成的新生骨量多于方盒形Carboncage。结论方盒形Carboncage具有良好的椎间支撑能力,而垂直圆柱体Harmscage的椎间融合效果更好。     

自体骨髓基质干细胞与钙磷陶瓷复合体在恒河猴腰椎前路融合中的实验研究

目的 评价自体骨髓基质干细胞（BMSCs）与钙磷生物陶瓷复合体的成骨效果。方法2003年3月至2005年4月,对9只成熟恒河猴行经腹膜外L3-4和L5-6腰椎间盘切除脊柱融合术。每只动物的两个脊柱节段随机接受3种治疗方法中的2种：自体髂骨移植（自体骨组,n=6）,空载体陶瓷移植物（陶瓷组,n=6）和骨髓基质干细胞-陶瓷复合体（BMSCs组,n=6）。自髂骨抽取骨髓,在含有成骨细胞诱导因子的培养液中体外扩增自体BMSCs,利用旋转培养方法构建骨髓基质干细胞-钙磷陶瓷复合体供移植用。实验动物在术后3个月处死,利用放射学、生物力学测试、组织学和组织形态计量学观察和分析脊柱融合节段。结果生物力学测试结果和组织学结果显示BMSCs组的椎体间脊柱融合效果明显好于陶瓷组;BMSCs组和自体骨组显示出近似的生物力学强度。BMSCs组和自体骨组的骨量显著多于陶瓷组;但陶瓷组的陶瓷材料残余量显著多于BMSCs组。结论在恒河猴椎体间脊柱融合模型中,自体骨髓基质干细胞和钙磷生物陶瓷复合体在移植入体内3个月内有良好的成骨并获得椎体间骨性融合。     

The use of rhBMP-2 in interbody fusion cages. Definitive evidence of osteoinduction in humans: a preliminary report

STUDY DESIGN: A prospective randomized controlled human clinical pilot trial. OBJECTIVES: To determine the feasibility of using rhBMP-2/collagen as a substitute for autogenous bone graft inside interbody fusion cages to achieve arthrodesis in humans. SUMMARY OF BACKGROUND DATA: Preclinical studies have shown rhBMP-2 to be an effective substitute for autogenous bone graft, but there are no studies to date documenting such efficacy for human spine fusion. METHODS: Fourteen patients with single-level lumbar degenerative disc disease refractory to nonoperative management were randomized to receive lumbar interbody arthrodesis with a tapered cylindrical threaded fusion cage filled with rhBMP-2/collagen sponge or autogenous iliac crest bone. Patients were evaluated with radiographs, sagittally reformatted computed tomography scans, and Short Form-36 and Oswestry outcome questionnaires. RESULTS: All 11 patients who received rhBMP-2 were judged by three independent radiologists to have solid fusions (at 6, 12, and 24 months postimplantation), whereas only 2 of the 3 control patients, who received the standard treatment of autogenous iliac crest bone, were deemed to be fused. The Oswestry Disability Questionnaire scores of the rhBMP-2 group improved sooner (after 3 months) than those of the autograft group, with both groups demonstrating similar improvement at 6 months. Short Form 36 scores continued to improve up to 24 months. CONCLUSION: The arthrodesis was found to occur more reliably in patients treated with rhBMP-2-filled fusion cages than in controls treated with autogenous bone graft, although the sample size was limited. There were no adverse events related to the rhBMP-2 treatment. This study is one of the first to show consistent and unequivocal osteoinduction by a recombinant growth factor in-humans.     

A preliminary comparative study of radiographic results using mineralized collagen and bone marrow aspirate versus autologous bone in the same patients undergoing posterior lumbar interbody fusion with instrumented posterolateral lumbar fusion.

BACKGROUND CONTEXT: Multiple bone graft substitutes for spinal fusion have been studied with varying results. PURPOSE: The purpose of this study was to assess the effectiveness of a mineralized collagen matrix combined with bone marrow, versus autologous bone, in the same patients undergoing a posterior lumbar interbody fusion and an instrumented posterolateral lumbar fusion. STUDY DESIGN/SETTING: A prospective, comparative study. PATIENT SAMPLE: Patients indicated for one-level posterior lumbar interbody fusion and instrumented posterolateral lumbar fusion, serving as self-controls. OUTCOME MEASURES: Thin-cut computed tomographic scans with sagittal reconstruction and plain radiographs, including lateral flexion/extension views were performed and assessed at 12 and 24 months after surgery. Oswestry Disability Index and Visual Analog Scale questionnaires were completed by all patients preoperatively and at 12 and 24 months after surgery. METHODS: After informed consent and failure of nonoperative treatment, 25 consecutive patients requiring one-level instrumented posterolateral fusion combined with posterior interbody fusion were enrolled in the study. Mineralized collagen bone graft substitute combined with bone marrow aspirate was used on one side of the posterolateral fusion, with iliac crest autograft on the contralateral side. RESULTS: A fusion rate of 84% (21/25) was achieved for the autologous bone grafts and 80% (20/25) for the bone graft substitute. The interbody fusion rate was 92% (23/25). Mean Oswestry Disability Index (ODI) scores decreased 57.2% at 12 months and 55.6% at 24 months, compared with baseline. CONCLUSIONS: Mineralized collagen bone graft substitute exhibited similar radiographic results compared with autograft in this model. Further trials incorporating bilateral fusion, as well as posterolateral fusion alone without interbody fusion are warranted to confirm the results of this study.     

Improved lumbar vertebral interbody fusion using rhOP-1: a comparison of autogenous bone graft, bovine hydroxylapatite (Bio-Oss), and BMP-7 (rhOP-1) in sheep

STUDY DESIGN: After disc removal and monosegmental instrumentation of the sheep lumbar spine, interbody fusion was compared for 6 months after administration of autogenous bone graft, hydroxylapatite, or rhOP-1. OBJECTIVE: To determine whether the use of rhOP-1 or hydroxylapatite would improve on the intercorporal fusion achieved by autologous bone grafting. SUMMARY OF BACKGROUND DATA: Spinal fusion often fails or shows loss of correction despite large-scale conventional techniques using posterior and anterior access. Also, additional operations to obtain bone grafts are required, which increase morbidity and strain for the patient, but do not always provide bone with sufficient primary stability and high osteogenic potential. METHODS: Vertebral fusion quality was examined by plain radiograph at 4-week intervals, by scintigraphy at 3 and 6 months, and by computed tomography scan, magnetic resonance imaging, biomechanical testing, and histologic evaluation. RESULTS: All examination methods demonstrated superior fusion after administration of rhOP-1, with radiologic fusion apparent at 4 months. Autologous bone grafts eventually produced bony healing in most cases, albeit of a lower quality than with rhOP-1. Hydroxylapatite use led only to the formation of a tight pseudarthrosis. CONCLUSIONS: The results indicate that rhOP-1 use is an appropriate method for improving interbody fusion in the sheep spine. In addition to offering the potential for improved bone healing, rhOP-1 use may permit less invasive surgery such as transpedicular fusion and the use of cages.     

Osteogenic protein versus autologous interbody arthrodesis in the sheep thoracic spine. A comparative endoscopic study using the Bagby and Kuslich interbody fusion device

STUDY DESIGN: Using an in vivo interbody arthrodesis model, the efficacy of the Bagby and Kuslich (BAK) device packed with recombinant human osteogenic protein-1 (rhOP-1) was evaluated. OBJECTIVES: To compare the efficacy of osteogenic protein with that of autograft for interbody arthrodesis, with fusion success based on biomechanical, histologic, and radiographic analyses. SUMMARY OF BACKGROUND DATA: The use of recombinant human bone morphogenetic proteins (rhBMPs) as osteoinductive bone graft substitutes or expanders has recently gained considerable research interest, particularly when applied in posterolateral arthrodesis. However, whether these results can be extrapolated to a successful interbody spinal arthrodesis remains uncertain. METHODS: Twelve sheep underwent a multilevel thoracic spinal decompression by thoracoscopic approach. Three noncontiguous destabilization sites (T5-T6, T7-T8, T9-T10) were prepared and randomly treated as follows. Control group treatments were nonsurgical, destabilization alone, and empty BAK. Experimental groups were treated with autograft alone, BAK device packed with autograft, or BAK device packed with rhOP-1. Four months after surgery, interbody fusion status was quantified by biomechanical testing, computed tomography, microradiography, and histomorphometry. RESULTS: Results of biomechanical analysis showed statistically higher segmental stiffness levels when comparing the control and experimental groups with four of the five testing methods (P < 0.05). Computed tomography and microradiography characterized destabilization alone as producing one fusion in six preparations; the empty BAK, two in six;, autograft alone, four in eight; BAK with autograft, five in eight; and BAK with rhOP-1 group, six in eight-all evidenced by woven trabecular bone spanning the fusion sites. Histomorphometry yielded significantly more trabecular bone formation at the fusion sites in the three experimental groups than in the two control groups (P < 0.05). CONCLUSIONS: Interbody spinal fusions showing biomechanical and histomorphometric equivalency to autologous fusions have been achieved with rhOP-1. The functional unit stability and histologic osteointegration evidenced by the BAK/rhOP-1 complex shows this interbody arthrodesis technique to be a viable alternative toconventional autologous iliac crest, thereby obviating the need for an iliac crest donor site and associated patient morbidity.     

Posterolateral lumbar intertransverse process spine arthrodesis with recombinant human bone morphogenetic protein 2/hydroxyapatite-tricalcium phosphate after laminectomy in the nonhuman primate.

STUDY DESIGN: A nonhuman primate lumbar intertransverse process arthrodesis model was used to evaluate recombinant human bone morphogenetic protein 2 (rhBMP-2) in a hydroxyapatite-tricalcium phosphate (HA-TCP) carrier as a complete bone graft substitute. OBJECTIVES: To assess the ability of a ceramic material to serve as a carrier for various doses of rhBMP-2 as a bone graft substitute in a primate model of posterolateral intertransverse process spinal fusion after laminectomy. SUMMARY OF BACKGROUND DATA: The reported non-union rates for posterolateral lumbar spine fusion with autogenous iliac crest bone range from 5-35%. Recombinant human bone morphogenetic protein 2 has shown potential to serve as a bone graft substitute for posterolateral intertransverse process spine fusion. Although a resorbable collagen sponge was a suitable carrier in rabbits and dogs, it was too compressible for the paraspinal muscles in rhesus monkeys. This failure of the collagen carrier has prompted evaluation of the feasibility of an alternative carrier material and the required dose of rhBMP-2. METHODS: Twenty-one adult rhesus monkeys underwent a laminectomy at L4-L5 followed by bilateral intertransverse process arthrodesis via the same midline incision (n = 16) or a minimally invasive video-assisted posterolateral approach (n = 5). Bone graft implants on each side consisted of either 5 cm3 of autogenous iliac crest bone or 60:40 HA-TCP blocks (1.2 x 0.5 x 3.7 cm) loaded with a solution containing 0, 6, 9, or 12 mg of rhBMP-2 per side. The monkeys were killed 24 weeks after surgery. Inspection, manual palpation, radiography, and histology were used to assess fusion and to detect any bony growth into the laminectomy defect. RESULTS: Fusion was not achieved in any of the monkeys treated with autogenous iliac crest bone graft. Both of the monkeys treated with the HA-TCP blocks with 0 mg rhBMP-2 achieved fusion. All 15 monkeys treated with the HA-TCP blocks and either of the three doses of rhBMP-2 achieved solid fusion. Two animals had extension of the fusion on one side because of malpositioned ceramic block. The results in animals fused via the minimally invasive video-assisted technique were the same as inthose fused with the open technique. Histologic analysis showed some ingrowth of bone into the ends but not-through the ceramic block in the absence of rhBMP-2. When the ceramic blocks were loaded with rhBMP-2 there was a dose-dependent increase in the amount and quality of bone throughout the ceramic carrier based on qualitative assessment. No significant bone encroachment on the exposed thecal sac through the laminectomy defect was observed in any of the monkeys. CONCLUSION: Hydroxyapatite-tricalcium phosphate proved to be a suitable carrier for rhBMP-2 in the posterolateral spine fusion model in rhesus monkeys. Even in the presence of a laminectomy defect, there was no evidence of bone induction outside the confines of the ceramic carrier.     

Efficacy of silicated calcium phosphate graft in posterolateral lumbar fusion in sheep.

BACKGROUND CONTEXT: Conditions requiring posterior lumbar spinal fusion remain a clinical challenge. Achieving arthrodesis using autogenous bone graft is inconsistent when rigid internal fixation such as transpedicular instrumentation is applied. Synthetic materials, particularly calcium phosphate-based ceramics, have shown promise for spine fusion applications, especially when combined with autograft. Silicate substitution has been shown to enhance the bioactivity of calcium phosphates and may obviate the need for autologous supplementation. PURPOSE: Determine efficacy of silicated calcium phosphate (Si-CaP) compared with autograft to generate solid lumbar fusion. STUDY DESIGN: Comparison of healing of instrumented posterolateral lumbar fusion in ewes at 2 and 6 months using Si-CaP or iliac crest autograft. METHODS: Eighteen skeletally mature ewes underwent implantation of either autograft or Si-CaP in the space spanning the L4-L5 transverse process. In vivo quantitative computed tomography (CT) scans were made at 2-month intervals and after euthanasia. Harvested spine segments were radiographed and biomechanically tested in bending at 6 months. Histological assessments were made at 2 and 6 months. RESULTS: Animals receiving Si-CaP graft were biomechanically and radiographically equivalent to those receiving autograft. Fusion mass density and volume were higher for the Si-CaP group throughout the healing period. Si-CaP regenerated normal bone tissue morphology, cellularity, and maturation with no inflammatory responses despite the fact that no autograft, bone marrow aspirate, or blood was mixed with the material. Histomorphometrically, fusion mass was higher for Si-CaP and bony bridging was equivalent when compared with autograft treatment. CONCLUSIONS: Si-CaP was biomechanically, radiographically, and histologically equivalent to autograft in generating a solid, bony, intertransverse process fusion in an ovine model. Both treatment groups achieved 100% bridging fusion after 6 months of healing.     

Osseointegration of autograft versus osteogenic protein-1 in posterolateral spinal arthrodesis: emphasis on the comparative mechanisms of bone induction.

BACKGROUND CONTEXT: Recent studies have documented increased fusion success afforded by bone morphogenetic proteins versus autogenous graft for posterolateral spinal arthrodesis. PURPOSE: The current study was designed to investigate the time-course maturation processes of lumbar posterolateral arthrodeses performed with Osteogenic Protein-1 (Stryker Biotech, Inc., Hopkinton, MA, USA) (rhOP-1) versus "gold standard" autograft. STUDY DESIGN: The primary focus of this study was to compare the histologic mechanisms of posterolateral osseointegration produced by "hot topic" growth factors. METHODS: A total of 36 coonhounds were equally divided into one of four postoperative time periods of 4, 8, 12 and 24 weeks (nine animals per period). Posterolateral arthrodesis treatments included 1) autograft alone, 2) autograft plus rhOP-1, or 3) rhOP-1 alone. The treatments and animals were divided such that a value of n=6 was obtained for each treatment group per time period and no one animal received the same treatment at both operative sites. Functional spinal unit (FSU) fusion status was assessed using radiographic analysis, biomechanical testing and undecalcified histopathologic and histomorphometric analyses. RESULTS: Radiographic differences in fusion maturation between the treatment groups were evident as early as the 4-week time interval and continued through the 24-week time period. The Osteogenic Protein-1 treatments demonstrated an accelerated rate of radiographic fusion by 4 weeks, which plateaued after the 8-week time period (22% autograft, 88% autograft/rhOP-1 and 66% rhOP-1). In contradistinction, the so-called "gold standard" autograft alone treatments reached a maximum of 50% fusion by the 6-month interval. Biomechanical testing of the FSUs indicated lower flexion-extension and axial rotation range of motion levels for both rhOP-1 treatments versus autograft alone at the 8- and 12-week time periods, respectively (p<.05). Histomorphometric analysis yielded no difference in the posterolateral trabecular bone area (mm(2)) between the three treatments (p>.05), and histopathology indicated no significant histopathologic changes. The most distinctive finding in this study deals with the mechanisms of posterolateral ossification. Based on plain and polarized light microscopy, bone induction and development for the rhOP-1 treatments, with and without autograft, was the result of intramembranous ossification, whereas the process of osseointegration for autograft alone was endochondral bone formation. By the 24-week interval, no discernable differences in trabecular histomorphology were evident based on the different mechanisms of ossification. CONCLUSIONS: This serves as the first study to document the mechanisms of bone induction and fusion maturation between posterolateral arthrodeses treated with autograft versus rhOP-1. The histological data served to corroborate the radiographic and biomechanical findings, because the rhOP-1 treatments consistently demonstrated increased fusion rates and lower range of motion levels compared with the autograft group, particularly at the 8-week postoperative time period. The improvements in these fusion criteria for Osteogenic Protein-1 versus autograft were considered secondary to the differing mechanisms of bone induction. When implanted for posterolateral arthrodesis, rhOP-1 induces an intramembranous healing response, obviating the need for the cartilage intermediate phases found in endochondral bone development. The mechanism of increased speed and incidence of fusion using growth factors (rhOP-1) is delineated by this comprehensive study of preferential intramembranous ossification.     

前路病灶清除植骨内固定术治疗胸腰椎结核

目的探讨在胸、腰椎结核外科治疗中,前路病灶清除植骨内固定术对清除结核病灶,对脊髓神经的减压及重建脊柱稳定性的重要性。方法对2000年10月~2004年6月共收治的胸、腰椎结核患者46例,采用前路病灶清除自体髂骨植骨38例,异体深冻骨植骨并胸、腰椎前路钛钢板内固定8例。结果经过平均18个月的随访,长达1~1.5年的抗结核治疗,44例患者结核治愈,植骨融合时间平均为5.2个月。术前截瘫、不全瘫或伴有神经症状者均有不同程度的恢复;1例内固定松动、异体深冻骨植骨未融合;1例复发,但其异体深冻骨植骨块及内固定位置良好,经继续抗结核治疗6个月后结核治愈。结论前路病灶清除,自体髂骨植骨,钛钢板内固定对胸、腰椎结核疗效肯定,异体深冻骨植骨存在融合慢或不融合的问题。     

A poly(propylene glycol-co-fumaric acid) based bone graft extender for lumbar spinal fusion: in vivo assessment in a rabbit model

Study design: An animal model of posterolateral intertransverse process lumbar spinal fusion compared fusion rates amongst autologous bone (group 1), a porous, bioabsorbable, scaffold based on the biopolymer, poly(propylene glycol-co-fumaric acid) (PPF) (group 2), and a combination of autograft and the bioabsorbable scaffold (group 3). Objectives: To evaluate the feasibility of augmenting spinal fusion with an osteoconductive and bioabsorbable scaffold as an alternative or as an adjunct, i.e., an extender, to autograft. Summary of background data: There is little preclinical data on applications of bioabsorable bone graft extenders in spinal fusion. Methods: New Zealand White rabbits underwent single-level lumbar posterolateral intertransverse process fusion. Animals were treated with one of three materials: autologous bone (group 1), a bioabsorable material based on PPF (group 2), and the PPF biopolymer scaffold with autologous bone graft (group 3). Animals were evaluated at 6 weeks, and fusion was evaluated by manual palpation, and radiographic, histologic, and histomorphometric analyses. Results: Radiographic and manual palpation showed evidence of fusion in all three groups. Histomorphometric measurement of bone ingrowth showed the highest quantity of new bone in group 3 (91%), followed by group 1 (72%) and group 2 (53%). Conclusions: Results of this study suggested that osteoconductive bioabsorbable scaffolds prepared from PPF might be used as an autograft extender when applied as an adjunct to spinal fusion.     

A prospective study of Autologous Growth Factors (AGF) in lumbar interbody fusion.

BACKGROUND: Numerous preclinical and clinical studies have reported on the use of platelet concentrates to promote tissue healing. The results in spinal fusion applications are limited and controversial. PURPOSE: The purpose of the current prospective clinical cohort study is to assess the effect of Autologous Growth Factors (AGF) on lumbar interbody fusion with specific attention paid to determination of clinical and radiographic outcomes. STUDY DESIGN/SETTING: Prospective clinical study PATIENT SAMPLE: Candidates for anterior-posterior lumbar fusion with diagnosis of degenerative disc disease and/or up to grade I spondylolytic spondylolisthesis based on positive provocative discography. OUTCOME MEASURES: Clinical (visual analogue pain scale/functional outcome assessment) and radiographic outcomes (fusion on computed tomography at 6 months and plain radiographs at 12 and 24 months). METHODS: Thirty-seven patients were assigned to standard anterior-posterior interbody fusion L2-S1 (single or two-level) using iliac crest bone graft (autograft group: 22 patients with 32 levels operated) or allograft combined with autogenous growth factors (AGF group: 15 patients with 25 levels operated). Radiographic outcomes were collected at 6 months postsurgery with computed tomography and at 12 and 24 months with plain radiographs. Pre- and postoperative clinical outcome measures included visual analog scores (VAS) for back and leg pain (0-10), SF-36 scores, and Oswestry disability determination. Average clinical and radiographic follow-up for the autograft group was 24.3+/-5.6 months (12-36 months) and AGF was 25.7+/-7.5 (6-40 months). RESULTS: Fusion incorporation at each end plate was determined at 56% in both autograft and AGF (p=NS) patients based on computed tomography at 6 months with minimal subsidence noted and no direct correlation between the incidence or degree of cage subsidence and bone graft technique. The 12- and 24-month radiographic results confirmed an 85% arthrodesis rate for the autograft patients, whereas the AGF patients had an 89% fusion rate (p=NS). Clinical outcomes were similar for both groups and no significant differences were noted for pain or functional outcome improvements. CONCLUSIONS: AGF combined with an allograft carrier is equivalent in radiographic and clinical outcomes to autograft in one- or two-level lumbar interbody fusion with supplemental posterior fixation and, thus, eliminates any morbidity from iliac crest bone graft harvesting. AGF combined with an appropriate carrier is a reasonable alternative to autograft and expensive bone induction technologies. Further research is still required to examine the optimum carriers, preparation and formulation, and platelet concentrations for this technology.     

干细胞技术结合新型可降解材料进行腰椎融合的临床研究

目的 探索富集骨髓干细胞技术进行腰椎融合治疗脊柱疾病的疗效.方法 腰椎退行性疾患患者56例,根据行下腰椎后路融合手术中植骨融合材料的不同,分为富集骨髓干细胞快速复合多孔β-磷酸三钙(13-TCP)复合材料组(复合材料组,n=30)和自体髂骨植骨组(自体骨组,n=26).对复合材料组富集前后骨髓体积、有核细胞(NCs)和碱性磷酸酶染色阳性的细胞集落(CFUs/ALP+)计数,分析富集效率;结合随访、影像学检查和Oswestry功能评分等综合评定疗效.结果 复合材料组术中平均抽取骨髓血(249±31)ml,富集技术平均回收(43±11)ml,NCs由(15.9±3.3)x106/ml浓缩至(44.1±10.8)×106/ml,富集后CFUs/ALP+数量由(118±86)/ml浓缩至(486±305)/ml.临床随访(26.3±7.5)个月.两组中患者的年龄、性别、病种分布及融合节段无显著差异,复合材料组与自体骨组融合率分别为93.3%和96.2%(P＞0.05).两组手术时间的差异也无统计学意义(P＞0.05).复合材料组术中患者的总出血量高于自体骨组(P＜0.01),但术中自体血回输可以将接近1/2的术中出血回输给患者.复合材料组术后骨髓采集部无血肿和慢性疼痛,伤口渗出或局部肿胀4例,均自行愈合;而自体骨组术后髂骨采集部血肿(15.4%)和慢性疼痛(26.9%),无伤口渗出的情况.两组间Oswestry功能评分的差异无统计学意义(P＞0.05).结论 富集骨髓干细胞技术可在术中一期应用,提高骨髓MSCs的浓度,安全、快速.富集骨髓干细胞快速复合多孔β-磷酸三钙后,可作为腰椎后外侧融合的植骨替代品.     

Effects of autogenous bone graft impaction and tricalcium phosphate on anterior interbody fusion in the porcine lumbar spine

Background Impaction grafting can be achieved inside the spinal fusion cages, but its effect on bone graft incorporation and spinal fusion has not been studied. Animals and methods We investigated the effect of impaction grafting on the bone graft healing and fusion potential of beta-tricalcium phosphate (beta-TCP) inside the carbon fiber reinforced spinal fusion device (Brantigan cage) in 10 Danish landrace pigs. Lumbar spine interbody fusion of L2/3, L4/5 and L6/7 using carbon fiber cages was performed on each pig. Cages filled with either loosely-packed autologous iliac bone graft, rod-impacted autologous bone graft or beta-TCP were randomly distributed to the three fusion levels. Half of the animals were followed for 8 weeks, and the other half for 16 weeks. Results Radiographs and CT evaluations showed that autograft levels had significantly better results than beta-TCP levels (p<0.001 Fisher's Exact Test). However, the difference between impacted and loosely-packed levels was not significant. Histomorphometric analysis showed no difference between the loosely-packed and impacted cages with regard to bone volume, bone marrow volume, cartilage and fibrous tissue volume, while both of the autograft levels differed from the beta-TCP levels in all of the aforementioned parameters. Fluorochrome studies demonstrated that bone mineral apposition rate was significantly higher in the impacted cages than in the loosely-packed cages at 16 weeks. Interpretation Manual impaction of autologous bone graft into the carbon fiber cages resulted in a faster mineral apposition rate by 16 weeks. Bone ingrowth and spinal fusion were not influenced by impaction grafting.     

Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow.

Hydroxyapatite is a synthetic bone graft, which is used for the treatment of bone defects and nonunions. However, it is a rather inert material with no or little intrinsic osteoinductive activity. Recombinant human osteogenic protein-1 (rhOP-1) is a very potent biological agent, that enhances osteogenesis during bone repair. Bone marrow contains mesenchymal stem cells, which are capable of new bone formation. Biosynthetic bone grafts were created by the addition of rhOP-1 or bone marrow to granular porous hydroxyapatite. The performance of these grafts was tested in a sheep model and compared to the results of autograft, which is clinically the standard treatment of bone defects and nonunions. A 3 cm segmental bone defect was made in the tibia and fixed with an interlocking intramedullary nail. There were five treatment groups: no implant (n=6), autograft (n=8), hydroxyapatite alone (n=8), hydroxyapatite loaded with rhOP-1 (n=8), and hydroxyapatite loaded with autologous bone marrow (n=8). At 12 weeks, healing of the defect was evaluated with radiographs, a torsional test to failure, and histological examination of longitudinal sections through the defect. Torsional strength and stiffness of the healing tibiae were about two to three times higher for autograft and hydroxyapatite plus rhOP-1 or bone marrow compared to hydroxyapatite alone and empty defects. The mean values of both combination groups were comparable to those of autograft. There were more unions in defects with hydroxyapatite plus rhOP-1 than in defects with hydroxyapatite alone. Although the differences were not significant, histological examination revealed that there was more often bony bridging of the defect in both combination groups and the autograft group than in the group with hydroxyapatite alone. Healing of bone defects, treated with porous hydroxyapatite, can be enhanced by the addition of rhOP-1 or autologous bone marrow. The results of these composite biosynthetic grafts are equivalent to those of autograft.     

Effects of autogenous bone graft impaction and tricalcium phosphate on anterior interbody fusion in the porcine lumbar spine

Background?Impaction grafting can be achieved inside the spinal fusion cages, but its effect on bone graft incorporation and spinal fusion has not been studied. Animals and methods?We investigated the effect of impaction grafting on the bone graft healing and fusion potential of ß-tricalcium phosphate (ß-TCP) inside the carbon fiber reinforced spinal fusion device (Brantigan cage) in 10 Danish landrace pigs. Lumbar spine interbody fusion of L2/3, L4/5 and L6/7 using carbon fiber cages was performed on each pig. Cages filled with either loosely-packed autologous iliac bone graft, rod-impacted autologous bone graft or ß-TCP were randomly distributed to the three fusion levels. Half of the animals were followed for 8 weeks, and the other half for 16 weeks. Results?Radiographs and CT evaluations showed that autograft levels had significantly better results than ß-TCP levels (p<0.001 Fisher's Exact Test). However, the difference between impacted and loosely-packed levels was not significant. Histomorphometric analysis showed no difference between the loosely-packed and impacted cages with regard to bone volume, bone marrow volume, cartilage and fibrous tissue volume, while both of the autograft levels differed from the ß-TCP levels in all of the aforementioned parameters. Fluorochrome studies demonstrated that bone mineral apposition rate was significantly higher in the impacted cages than in the loosely-packed cages at 16 weeks. Interpretation?Manual impaction of autologous bone graft into the carbon fiber cages resulted in a faster mineral apposition rate by 16 weeks. Bone ingrowth and spinal fusion were not influenced by impaction grafting.     

2000 Young Investigator Research Award winner. Evaluation of OP-1 as a graft substitute for intertransverse process lumbar fusion

STUDY DESIGN: An established rabbit intertransverse process lumbar fusion model was used to evaluate osteogenic protein (OP)-1 as a potential graft substitute. OBJECTIVES: To determine whether OP-1 is effective in producing intertransverse process lumbar fusion in a rabbit model. SUMMARY OF BACKGROUND DATA: Autogenous iliac crest bone is the gold standard in grafting material for inducing intertransverse process fusion. However, bone graft substitutes are being considered as supplementary or alternative means to achieve such fusion with less morbidity. Relatively little research has been undertaken to investigate the efficacy of OP-1 in this role. METHODS: Single-level intertransverse process lumbar fusions were performed at L5-L6 of 31 New Zealand White rabbits. These were divided into three study groups: autograft, carrier alone, and carrier with OP-1. The animals were killed 5 weeks after surgery. Resultant fusion masses were evaluated by manual palpation, radiography, biomechanical multidirectional flexibility testing, and histology. RESULTS: Seven rabbits (23%) were excluded because of complications. Of the remaining 24 rabbits, 5 (63%) of the 8 in the autograft group had fusion detected by manual palpation, none (0%) of the 8 in the carrier-alone group had fusion, and all 8 (100%) in the OP-1 group had fusion. Radiographs were 55% sensitive and 92% specific for determining fusion. Biomechanical testing results correlated well with those of manual palpation. Histologically, autograft specimens were predominantly fibrocartilage, OP-1 specimens were predominantly maturing bone, and carrier-alone specimens did not show significant bone formation. CONCLUSIONS: OP-1 was found to reliably induce solid intertransverse process fusion in a rabbit model at 5 weeks.     

Endoscopic instrumented posterolateral lumbar fusion with Healos and recombinant human growth/differentiation factor-5

OBJECTIVE: The goal of this study was to use a minimally invasive endoscopic surgical technique in a sheep model to evaluate the efficacy of an osteoinductive growth factor, recombinant human growth/differentiation factor-5 (also designated MP52), and an osteoconductive matrix formulation (Healos; DePuy AcroMed, Inc., Mountain View, CA) for inducing and facilitating bone formation. METHODS: Twelve mature sheep underwent bilateral posterolateral lumbar fusion and pedicle screw fixation via a posterior endoscopic approach. Each sheep received two different types of graft material, autogenous iliac crest bone, or a bone graft substitute (MP52 with Healos), inserted into the right and left sides of the spine in an alternating fashion. Groups of four sheep were killed at 2, 4, and 6 months postoperatively for manual, radiographic, and histological evaluation. RESULTS: No neurological impairments, infections, or other complications were observed. After 2 months, partial fusion on both sides was observed, but radiographic evaluation showed greater bone growth on the side that received the bone graft substitute. Solid posterolateral fusion was observed in both autograft and bone graft substitute sites at 4 and 6 months, and autograft and Healos MP52 fusion sites were essentially the same at histological examination. There was no abnormal overgrowth of new bone from either of these two materials. CONCLUSION: Endoscopic posterolateral lumbar arthrodesis and instrumentation is feasible, safe, and effective in a sheep model. Healos is a useful bonding agent that mimics natural bone in posterolateral intertransverse fusion sites. Combined with MP52, it produced fusion comparable to that of autogenous bone graft. Minimally invasive techniques and bone graft substitutes could eliminate morbidity and increase the likelihood of successful fusion.     

The First Clinical Trial of Beta-Calcium Pyrophosphate as a Novel Bone Graft Extender in Instrumented Posterolateral Lumbar Fusion

Background

Porous β-calcium pyrophosphate (β-CPP) was developed to improve the fusion success of posterolateral lumbar fusion (PLF). The possibility of accomplishing PLF using a mixture of porous β-CPP and iliac bone was studied. This paper reports the radiologic results of PLF using the β-CPP plus autograft for lumbar degenerative disease as a bone graft extender.

Methods

A prospective, case-matched, radiographic study evaluating the results of short segment lumbar fusion using a β-CPP plus autograft was performed to compare the efficacy of β-CPP plus autograft with that of an autograft alone for short segment lumbar fusion. Thirty one consecutive patients (46 levels) underwent posterolateral fusion with pedicle screw fixation and additional posterior lumbar interbody fusion. In all patients, 3 mL of β-CPP plus 3 mL of autogenous bone graft was placed randomly in one side of a posterolateral gutter, and 6 mL of autogenous iliac bone graft was placed on the other. The fusion rates, volumes of fusion masses, and bone absorption percentage were evaluated postoperatively using simple radiographs and 3 dimensional computed tomography (3D-CT) scans.

Results

The control sides treated with an autograft showed significantly better Lenke scores than the study sides treated with β-CPP at 3 and 6 months postoperatively, but there was no difference between the two sides at 12 months. The fusion rates (confirmed by 3D-CT) were 87.0% in the β-CPP group and 89.1% in the autograft group, which were not significantly different. The fusion mass volumes and bone absorption percentage at 12 months postoperatively were 2.49 mL (58.4%) and 1.89 mL (69.5%) for the β-CPP and autograft groups, respectively, and mean fusion mass volume was significantly higher in the β-CPP group.

Conclusions

β-CPP combined with an autograft is as effective as autologous bone for grafting during instrumented posterolateral spinal fusion. These findings suggest that β-CPP bone chips can be used as a novel bone graft extender for short-segment posterolateral spinal fusion.     

Spinal fusion using an autologous growth factor gel and a porous resorbable ceramic

Augmenting healing through a single application of an exogenous growth factor or bone morphogenetic protein is not a new concept. The use of autologous growth factors through platelet isolation and concentration provides multiple endogenous growth factors to the healing site. A posterolateral fusion model in aged sheep (5- to 6-year-old ewes) was used to examine the effects of the addition of growth factors through autologous platelet isolation on the biomechanic and histologic properties of the fusion using a resorbable coral bone graft substitute. At 6 months the combination of autologous growth factors to the Pro Osteon 500R plus aspirated bone marrow resulted in the greatest bending stiffness but not ultimate load. Autologous growth factors can be isolated from platelets and concentrated to provide multiple growth factors to the fusion site to aid in spinal fusion.