Grafting long bone fractures with demineralized bone matrix putty enriched with bone marrow: pilot findings

In this pilot study, the preliminary effectiveness of a composite graft consisting of demineralized bone matrix (DBM) putty (Grafton DBM) and aspirated bone marrow was evaluated for treating long bone fractures. Patients were ssigned randomly to treatment with the DBM putty composite (n = 10) or iliac crest autograft (n = 8), and had a minimum of 12 months of radiographic follow-up. Ninety percent of DBM patients (9/10) achieved full bone formation compared to 75% of autograft patients (6/8) (P = .41). Additionally, all 10 DBM patients were healed compared with 63% of autograft patients (5/8) (P = .07). These findings suggest that DBM putty enriched with bone marrow may be comparable to autograft for treating long bone fractures.     

The efficacy of a nanosynthetic bone graft substitute as a bone graft extender in rabbit posterolateral fusion

BACKGROUND CONTEXTSynthetic bone graft substitutes are commonly used in spinal fusion surgery. Preclinical data in a model of spinal fusion to support their efficacy is an important component in clinical adoption to understand how these materials provide a biological and mechanical role in spinal fusion.PURPOSETo evaluate the in vivo response of a nanosynthetic silicated calcium phosphate putty (OstP) combined with autograft compared to autograft alone or a collagen-biphasic calcium phosphate putty (MasP) combined with autograft in a rabbit spinal fusion model.STUDY DESIGNEfficacy of a nanosynthetic silicated calcium phosphate putty as an extender to autograft was studied in an experimental animal model of posterolateral spinal fusion at 6, 9, 12 and 26 weeks, compared to a predicate device.METHODSSkeletally mature female New Zealand White rabbits (70) underwent single level bilateral posterolateral intertransverse process lumbar fusion, using either autograft alone (AG), a nanosynthetic silicated calcium phosphate putty (OstP) combined with autograft (1:1), or a collagen-biphasic calcium phosphate putty (MasP) combined with autograft (1:1). Iliac crest autograft was harvested for each group, and a total of 2 cc of graft material was implanted in the posterolateral gutters per side. Fusion success was assessed at all time points by manual palpation, radiographic assessment, micro-CT and at 12 weeks only using non-destructive range of motion testing. Tissue response, bone formation and graft resorption were assessed by decalcified paraffin histology and by histomorphometry of PMMA embedded sections.RESULTSAssessment of fusion by manual palpation at the 12 week endpoint showed 7 out of 8 (87.5%) bilateral fusions in the OstP extender group, 4 out of 8 (50%) fusions in the MasP extender group, and 6 out of 8 (75%) fusions in the autograft alone group. Similar trends were observed with fusion scores of radiographic and micro-CT data. Histology showed a normal healing response in all groups, and increased bone formation in the OstP extender group at all timepoints compared to the MasP extender group. New bone formed directly on the OstP granule surface within the fusion mass while this was not a feature of the Collagen-Biphasic CaP material. After 26 weeks the OstP extender group exhibited 100% fusions (5 out of 5) by all measures, whereas the MasP extender group resulted in bilateral fusions in 3 out of 5 (60%), assessed by manual palpation, and fusion of only 20 and 0% by radiograph and micro-CT scoring, respectively. Histology at 26 weeks showed consistent bridging of bone between the transverse processes in the Ost P extender group, but this was not observed in the MasP extender group.CONCLUSIONSThe nanosynthetic bone graft substituted studied here, used as an extender to autograft, showed a progression to fusion between 6 and 12 weeks that was similar to that observed with autograft alone, and showed excellent fusion outcomes, bone formation and graft resorption at 26 weeks.CLINICAL SIGNIFICANCEThis preclinical study showed that the novel nanosynthetic silicated CaP putty, when combined with autograft, achieved equivalent fusion outcomes to autograft. The development of synthetic bone grafts that demonstrate efficacy in such models can eliminate the need for excessive autograft harvest and results from this preclinical study supports their effective use in spinal fusion surgery.     

Evaluation of a new formulation of demineralized bone matrix putty in a rabbit posterolateral spinal fusion model

Background contextAlternatives to autologous bone graft (ABG) with osteoconductive, osteoinductive, and osteogenic potential continue to prove elusive. Demineralized bone matrix (DBM) however, with its osteoconductive and osteoinductive potential remains a viable option to ABG in posterolateral spine fusion.PurposeTo compare the efficacy of a new formulation of DBM putty with that of ABG in a rabbit posterolateral spinal fusion model.Study designEfficacy of a new formulation of DBM was studied in an experimental animal posterolateral spinal fusion model.MethodsTwenty-four male New Zealand White rabbits underwent bilateral posterolateral spine arthrodesis of the L5–L6 intertransverse processes, using either ABG (control group, n=12) or DBM (DBM made from rabbit bone) putty (test group, n=12). The animals were killed 12 weeks after surgery and the lumbar spines were excised. Fusion success was evaluated by manual palpation, high resolution X-rays, microcomputed tomography imaging, biomechanical four-point bending tests, and histology.ResultsTwo animals were lost because of anesthetic related issues. Manual palpation to assess fusion success in the explanted lumbar spines showed no statistical significant difference in successful fusion in 81.8% (9/11) of DBM group and 72.7% (8/11) of ABG group (p=.99). Reliability of these assessments was measured between three independent observers and found near perfect agreement (intraclass correlation cofficient: 0.92 and 0.94, respectively). Fusion using high resolution X-rays was solid in 10 of the DBM group and 9 of the ABG group (p=.59). Biomechanical testing showed no significant difference in stiffness between the control and test groups on flexion, extension, and left lateral and right lateral bends, with p values accounting for .79, .42, .75, and .52, respectively. The bone volume/total volume was greater than 85% in the DBM treated fusion masses. Histologic evaluation revealed endochondral ossification in both groups, but the fusion masses were more mature in the DBM group.ConclusionsThe DBM putty achieved comparable fusion rates to ABG in the rabbit posterolateral spinal fusion model.     

A 2-year follow-up pilot study evaluating the safety and efficacy of op-1 putty (rhbmp-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions

The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to a multitude of investigations into their use as bone graft substitutes in spinal surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety and efficacy of BMP-7 (osteogenic protein 1, OP-1), in the form of a putty, combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent a laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements, followed by an intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and SF-36 outcome forms, and radiographically using static and dynamic radiographs to assess their fusion status over a 2-year period. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed eight of the nine evaluable patients (89%) obtained at least a 20% improvement in their preoperative Oswestry score, while five of ten patients (50%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in seven of the ten patients (70%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the statistical superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was 45%. There were no adverse events related to the OP-1 putty implant in this study, which supports findings in other studies suggesting the safety of bone morphogenetic proteins in spinal surgery.     

A pilot safety and efficacy study of OP-1 putty (rhBMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions

The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to an increasing interest in the potential for their use in fusion surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety of one such BMP—osteogenic protein 1, in the form of OP-1 putty—combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements followed by intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and radiographically using static and dynamic radiographs to assess their fusion status. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. In addition to bridging bone, less than or equal to 5° of angular motion and less than or equal to 2 mm of translation were required to classify the patients as successfully fused, as per the definition of successful fusion provided by the FDA for use in clinical trials involving investigational devices to attain spinal fusion. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed 9 of the 12 patients (75%) obtained at least a 20% improvement in their preoperative Oswestry score, while 6 of 11 patients (55%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in 10 of the 11 patients (91%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was approximately 45%. The lack of adverse events related to the OP-1 putty implant in this study is in agreement with other studies supporting the safety of bone morphogenetic proteins in spinal surgery.     

Augmented demineralized bone matrix: a potential alternative for posterolateral lumbar spinal fusion

Variable osteoinductive potential has been reported between and within production lots of different demineralized bone matrix (DBM) products. This study compared fusion rates of different manufactured lots and augmented formulations of DBM with a dose-response curve of recombinant human bone morphogenetic protein 2 (rhBMP-2) on inactivated DBM carrier in a posterolateral fusion rat model. Lumbar fusions were performed in 145 rats. In the control rats, we implanted autograft, graft alternative, including inactivated DBM, or nothing (ie, no graft). In the study rats, we implanted 1 of 2 BioSETR (RTI Biologics, Alachua, Florida) DBM lots, growth factor-enriched DBM, and inactivated DBM plus rhBMP-2 in different concentrations. Manual palpation revealed fusion rates of 25% (autograft), 0% (inactivated DBM), 17% (DBM donor A), and 36% (DBM donor B). The fusion rate of the most enhanced donor B graft (83%) was higher (P<.05) than that of autograft or unenhanced DBM. Inactivated DBM plus rhBMP-2 fused between 45% and 100%. There was no significant difference between DBM plus rhBPM-2 and the highest enrichment group of donor B. Differences between 2 DBM lots in an athymic rat ectopic bone formation model also were found in the spine fusion model. Enhanced DBM formulations were comparable with inactivated DBM plus rhBMP-2 with respect to performance and could represent a bone graft alternative in spine fusion.     

Use of biphasic calcium phosphate versus demineralized bone matrix: retrospective clinical and CT analysis of posterolateral fusion results

Purpose

Bone graft extenders have been developed to prevent donor site morbidity associated with iliac crest bone graft, but few studies compared the efficacy of various substitutes. Our purpose was to determine fusion rate and clinical outcome in patients undergoing lumbar arthrodesis using demineralized bone matrix (DBM) and biphasic calcium phosphate (BCP).

Methods

Patients with degenerative spondylolisthesis undergoing one-level or two-level arthrodesis of lumbar spine were retrospectively reviewed. Two treatment groups placed either BCP or DBM, in addition to local autograft in lumbar posterolateral space. Three-dimensional CT exam and dynamic flexion–extension radiographs at postoperative 2-year were assessed for posterolateral fusion status and pain scale and Oswestry Disability Index (ODI) for clinical outcome.

Results

Of the 148 patients reviewed (including 23 in one- and 58 patients in two-level in BCP group, and 47 in one- and 20 patients in two-level in DBM group), no significant differences were found in terms of age, sex, BMI, smoking, diabetes, steroids, number of level fused, non-union rate or revision surgery between BCP and DBM groups. Significantly improved pain scale of back and leg and ODI were found in both groups postoperatively without group difference. We found a comparable fusion rate in one-level surgery (100% versus 93.6%) and a superior fusion rate of BCP group in two-level surgery (98.3% versus 80.0%, p = 0.01).

Conclusion

Being a bone graft extender without osteoinductive property, with local autograft, BCP is comparable to DBM for one- and superior for two-level fusion. No significant difference was found in clinical outcomes.

     

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.     

Autograft versus allograft with or without demineralized bone matrix in posterolateral lumbar fusion in rabbits. Laboratory investigation

OBJECT: Posterolateral spinal fusions are performed to treat different spinal disorders. Autograft continues to be the gold standard; it is, however, associated with donor site morbidity and limited sources. Allograft has been used, but has been reported to result in lower fusion rates. Demineralized bone matrix (DBM) has also been used and reportedly increases the fusion rate in a variety of critical defect models. Different forms of DBM are available, not all have been independently studied. To evaluate the effect of a xenogenic DBM added to allograft on the fusion rate of posterolateral lumbar spine arthrodesis the authors designed an experimental study comparing posterolateral fusion rate using autograft, allograft, and allograft plus a xenogenic DBM in a validated animal model. METHODS: A bilateral, 1-level (L4-5) intertransverse process fusion was performed in 45 male New Zealand rabbits. Iliac crest bone graft was harvested bilaterally from each rabbit. The rabbits were randomly assigned to 3 groups: Group I, Autograft, 15 rabbits; Group II, Allograft, 15 rabbits; and Group III, Allograft plus DBM in a paste form (Dynagraft). The animals were killed 8 weeks after surgery. Fusion was assessed radiographically and by manual palpation by 2 independent observers. The results were analyzed using the Fisher exact test and chi-square test. RESULTS: The fusion rate was 46.6% (7 of 15 rabbits) in the autograft group, 33.3% (5 of 15 rabbits) in the allograft group, and 33.3% (5 of 15 rabbits) in the allograft plus DBM group (p > 0.05). CONCLUSIONS: Autograft produced a higher fusion rate than allograft in this spinal fusion rabbit model, but the difference was not statistically significant. Allograft plus xenogenic DBM showed the same fusion rate as allograft alone.     

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.     

The failure of ethylene oxide gas-sterilized freeze-dried bone graft for thoracic and lumbar spinal fusion

Thirty-seven patients underwent posterior and/or posterolateral spinal fusion using ethylene oxide gas-sterilized freeze-dried bank bone graft. Thirteen patients had discogenic back pain, eight with prior failed laminectomy procedures, and five undergoing initial spinal surgery. Six patients had isthmic spondylolisthesis, three with associated radicular complaints, and two patients had degenerative spondylolisthesis. Seven patients with spinal fractures and nine patients with scoliosis underwent spinal fusion with associated instrumentation. Pseudarthroses were detected in 28 patients (76%), and 18 patients (49%) underwent pseudarthrosis repair procedures using autogenous iliac bone graft. At surgery, the prior gas-sterilized freeze-dried bone graft was noted to have been almost completely resorbed. Ethylene oxide sterilization has been found experimentally in animal models to damage the osteoinductive ability of bone grafts. Ethylene oxide gas-sterilized freeze-dried bank bone graft is inferior to autogenous bone graft or bank bone graft preserved and/or sterilized by other methods. Its use in thoracic or lumbar posterior or posterolateral fusion cannot be recommended.     

Adjuncts in posterior lumbar spine fusion: comparison of complications and efficacy

Purpose

The purpose of this study was to define the efficacy of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) and Demineralized Bone Matrix (DBM) compared to autograft in posterior lumbar spine fusion by comparing complication rates.

Methods

During a 7-year period (2003–2009), all patients undergoing posterior lumbar fusion were retrospectively evaluated within a large orthopedic surgery private practice. Patient demographics, comorbidities, number of levels, type of surgery, and types of bone void filler and osteobiologics were analyzed. Complications were defined as reoperation secondary to failed symptomatic fusion, hyper-reaction with fluid collections, bone overgrowth, and infections.

Results

1,398 patients were evaluated with 41.1?% males and 58.9?% females. Mean age was 60?years and BMI 30.6?kg/m2. Patients were subdivided in treatment groups: rhBMP-2, 947 (67.7?%), DBM 306 (21.9?%), and autograft 145 (10.4?%). The overall infection rate was 2.1?%. No significant differences were found between the three groups. The incidence of seroma formation was higher in the BMP group (3.2?%) than in the DBM or autograft group (2.0 and 1.4?%, respectively) but this was not significant (p?=?0.286 and p?=?0.245, respectively). 103 patients (7.4?%) underwent redo surgery for clinically significant nonunion. We found significantly fewer nonunions (4.3?%) in the rhBMP-2 group (p?Conclusion ICBG is the gold standard. DBM leads to comparable fusion rates and does not increase infection or seroma formation. rhBMP-2 supplementation instead of ICBG or bone marrow aspirate results in higher fusion rates compared to autograft alone or autograft plus DBM.     

Posterolateral spinal fusion in a rabbit model using a collagen–mineral composite bone graft substitute

Choosing the appropriate graft material to participate in the healing process in posterolateral spinal fusion continues to be a challenge. Combining synthetic graft materials with bone marrow aspirate (BMA) and autograft is a reasonable treatment option for surgeons to potentially reduce or replace the need for autograft. FormaGraft, a bone graft material comprising 12% bovine-derived collagen and 88% ceramic in the form of hydroxyapatite (HAp) and beta tricalcium phosphate (β-TCP) was evaluated in three possible treatment modalities for posterior spinal fusion in a standard rabbit model. These three treatment groups were FormaGraft alone, FormaGraft soaked in autogenous BMA, and FormaGraft with BMA and iliac crest autograft. No statistically demonstrable benefits or adverse effects of the addition of BMA were found in the current study based on macroscopic, radiology or mechanical data. This may reflect, in part, the good to excellent results of the collagen HA/TCP composite material alone in a well healing bony bed. Histology did, however, reveal a benefit with the use of BMA. Combining FormaGraft with autograft and BMA achieved results equivalent to autograft alone. The mineral and organic nature of the material provided a material that facilitated fusion between the transverse processes in a standard preclinical posterolateral fusion model.     

New formulations of demineralized bone matrix as a more effective graft alternative in experimental posterolateral lumbar spine arthrodesis

STUDY DESIGN: A rabbit model of posterolateral intertransverse process spine arthrodesis was used. OBJECTIVE: To determine the efficacy of two new formulations of demineralized bone matrix. SUMMARY OF BACKGROUND DATA: The flowable gel form of Grafton (Osteotech, Eatontown, NJ) demineralized bone matrix has been shown to have osteoinductive properties in various models and currently is used clinically as bone graft material in posterolateral lumbar spine arthrodesis. Two new formulations of Grafton, one made of flexible sheets (Flex) and the other made in a malleable consistency (Putty), have improved handling characteristics compared with the gel form. METHODS: In this study, 108 New Zealand white rabbits underwent bilateral posterolateral intertransverse spine arthrodesis at L5-L6 using autogenous iliac crest bone graft alone (control), one of the new forms of demineralized bone matrix (DBM; made from rabbit bone) alone or in combination with autogenous iliac crest bone. Rabbits were killed 6 weeks after surgery. The lumbar spines were excised, and fusion success or failure was determined by manual palpation and radiography. Specimens also were processed for undecalcified histologic analysis. RESULTS: Manual palpation of the harvested lumbar spines revealed that the fusion rates of the Flex-DBM/Auto group (9/9, 100%) and Putty-DBM/Auto group (10/10, 100%) were superior (P < 0.01) to those of the Auto/control group (3/9, 33%). As a stand-alone graft substitute, Flex-DBM performed superiorly with a fusion rate of 11/11 (100%) compared with that of Putty-DBM (10/12, 83%) and Gel-DBM (7/12, 58%). The devitalized version of Flex-DBM had a fusion rate of 4/11 (36%), which was comparable with the devitalized Putty-DBM rate of 4/12 (33%). Both were superior (P < 0.05) to the devitalized Gel-DBM rate of 0/12 (0%). More mature fusions with greater amounts of trabecular bone were present radiographically and histologically in rabbits that received all forms of demineralized bone matrix than in those in which autograft was used. CONCLUSIONS: The new flexible sheet and malleable putty forms of demineralized bone matrix were effective as graft extender and graft enhancer in a model of posterolateral lumbar spine fusion. These newer formulations of Grafton appear to have a greater capacity to form bone than the gel form or autogenous bone graft alone in this model.     

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.     

An analysis of noninstrumented posterolateral lumbar fusions performed in predominantly geriatric patients using lamina autograft and beta tricalcium phosphate

BACKGROUND CONTEXT: The artificial bone-volume expander, beta tricalcium phosphate (B-TCP, Vitoss, OrthoVita, Malvern, PA), is increasingly used to supplement autograft in posterolateral lumbar fusions. PURPOSE: To determine fusion rates/outcomes using B-TCP/autograft. STUDY DESIGN/SETTING: Fusion rates and outcomes were assessed for 60 predominantly geriatric patients undergoing multilevel lumbar laminectomies and 1- to 2-level noninstrumented fusions using B-TCP/autograft. PATIENT SAMPLE: Patients on average were 70 years old. OUTCOME MEASURES: Odom's criteria and Short-Form 36 (SF-36) outcomes were studied 2 years postoperatively. METHODS: Sixty patients underwent an average of 5.4-level laminectomies with 1- to 2-level noninstrumented fusions. Based on dynamic X-ray/magnetic resonance/computed tomography (CT) studies, laminectomies addressed multilevel stenosis (60 patients), ossification of the yellow ligament (46 patients), disc herniations (20 patients), or synovial cysts (8 patients), and fusions addressed degenerative spondylolisthesis (48 patients), spondylolisthesis/lysis (2 patients), or degenerative scoliosis (10 patients). The fusion mass on each side contained half of all harvested autograft combined with one to 1.5 strips of B-TCP (saturated in 10cc of bone marrow aspirate/strip). Fusion rates were documented by two independent neuroradiologists using both dynamic X-rays, and thin-cut CT (2-dimensional/3-dimensional CT) studies obtained up to 2 years postoperatively. Odom's criteria and SF-36 outcomes were assessed over the same interval. RESULTS: Pseudarthrosis was documented in nine (15%) patients. Two years postoperatively, Odom's criteria revealed 28 excellent, 23 good, 5 fair, and 4 poor results, whereas SF-36 data revealed improvement on 6 of 8 Health Scales in all patients. CONCLUSIONS: A 15% pseudarthrosis rate followed multilevel laminectomy and 1- to 2-level noninstrumented posterolateral fusion using lamina autograft/B-TCP.     

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.     

In vivo evaluation of coralline hydroxyapatite and direct current electrical stimulation in lumbar spinal fusion.

STUDY DESIGN: An animal model of posterolateral intertransverse process lumbar spinal fusion using autologous bone, coralline hydroxyapatite, and/or direct current electrical stimulation. OBJECTIVES: To evaluate the effect of an osteoconductive bone graft substitute and direct-current electrical stimulation on the rate of pseudarthrosis in a rabbit spinal fusion model. SUMMARY OF BACKGROUND DATA: Conventional techniques for the surgical treatment of degenerative conditions in the lumbar spine have a substantial failure rate and associated morbidity. Bone graft substitutes and electrical stimulation are alternative techniques to enhance fusion rates and limit the morbidity associated with posterolateral intertransverse process fusion using autologous iliac crest bone graft. METHODS: Fifty-three adult female New Zealand White rabbits underwent single-level lumbar posterolateral intertransverse process fusion. Animals were assigned to one of four groups using either autologous bone (Group I), coralline hydroxyapatite with autologous bone marrow aspirate (Group II), coralline hydroxyapatite with a 40-microA implantable direct current electrical stimulator and bone marrow aspirate (Group III), or coralline hydroxyapatite with a 100-microA implantable direct current electrical stimulator and bone marrow aspirate (Group IV). Animals were killed at 8 weeks, and fused motion segments were subjected to manual palpation, mechanical testing, and radiographic and histologic analysis to assess the fusion mass. RESULTS: Successful fusion was achieved in 57% (8/14) of animals in Group I, 25% (3/12) in Group II, 50% (6/12) in Group III, and 87% (13/15) in Group IV. Mean stiffness and ultimate load to failure were significantly higher in Group IV than in all other groups (P < 0.05). Histologic analysis demonstrated a qualitative increase in fusion mass in Group IV versus all other groups. CONCLUSIONS: Direct-current electrical stimulation increased fusion rates in a dose-dependent manner in a rabbit spinal fusion model. Coralline hydroxyapatite is an osteoconductive bone graft substitute, and thus requires an osteoinductive stimulus to ensure reliable fusion rates. Furthermore, coralline hydroxyapatite and direct current electrical stimulation can be used together to increase fusion rates in a rabbit spinal fusion model while avoiding the morbidity associated with harvesting iliac crest bone.     

rhBMP-2 enhancement of posterolateral spinal fusion in a rabbit model in the presence of concurrently administered doxorubicin.

BACKGROUND CONTEXT: Spinal fusions can be necessary in patients undergoing chemotherapy with doxorubicin. In a previous study, doxorubicin was shown to decrease spinal fusion rates in a rabbit model of lumbar intertransverse process spinal fusion with autograft iliac crest bone. In the current study, we determine whether spinal fusion with recombinant human bone morphogenetic protein-2 (rhBMP-2) can overcome the inhibitory effect of doxorubicin in spinal fusion. PURPOSE: To determine if rhBMP-2 can overcome the inhibitory effects of doxorubicin (adriamycin) in an animal model of posterolateral spinal fusion. STUDY DESIGN/SETTING: Prospective, controlled, rabbit model of posterolateral lumbar fusion. OUTCOME MEASURES: Spine fusion was assessed by manual palpation (by observers blinded to the treatment group) at the level of arthrodesis. Fusion was graded according to a five-tiered classification (0-4). Posteroanterior radiographs of the excised spines were also graded in a blinded fashion using a six-point scoring system (0-5) devised to describe the amount of bone observed between the L5-L6 transverse processes. METHODS: Thirty-two New Zealand White rabbits underwent posterolateral fusion at L5-L6 with either autograft (iliac crest autograft bone) or rhBMP-2 (rhBMP-2/absorbable collagen sponge (0.86 mg/level). All animals received a dose of doxorubicin (2.5 mg/kg) known to inhibit spine fusion via the central vein of the ear immediately postoperatively. Five weeks postoperatively the rabbits were euthanized. Spine fusion was assessed by manual palpation, and graft quality was assessed with posteroanterior radiographs. RESULTS: Four of the 16 spines (25%) in the autograft group and 16 of the 16 spines (100%) in the rhBMP-2 group fused in the presence of doxorubicin administration (p<.05). There was significantly increased bone formation in the rhBMP-2 group (p<.05). One unilateral, subclinical wound infection was observed in each group at the time of euthanization (autograft [n=1, 6%] and rhBMP-2 [n=1, 6%]). CONCLUSIONS: We confirm that when autograft is used, doxorubicin decreases spinal fusion rate (25%) compared with historical controls (60-75%). More importantly, using rhBMP-2 overcomes the inhibitory effect of doxorubicin, resulting in 100% fusion in our animal model. This study suggests that rhBMP-2 has the potential to improve fusion rates in human patients undergoing chemotherapy with doxorubicin.     

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.