丝素蛋白增强型磷酸钙复合rhBMP-2用于绵羊腰椎椎体间融合的实验研究

目的 评价可注射丝素蛋白增强型磷酸钙(silk fibroin/calcium phosphate cement,SF/CPC)复合人重组骨形态发生蛋白-2(recombinant human bone morphogenetic protein-2,rhBMP-2)应用于绵羊腰椎椎体间融合的效果.方法 24只绵羊均建立L1.2、L3.4和L5.6前路椎体间融合模型.每只绵羊的3个腰椎间隙随机植入SF/CPC、CPC/rhBMP-2、SF/CPC/rhBMP-2和自体髂骨中的3种.分别于术后6个月和12个月各处死12只绵羊.每个时段均获得36个腰椎手术节段,每种材料9个节段.通过大体观察、手触检测、CT扫描、非破坏性生物力学测试和组织学观察分析脊柱融合状况.结果 术后6个月时,手触检测SF/CPC、CPC/rhBMP-2、SF/CPC/rhBMP-2以及髂骨的融合率分别为0、33.33%(3/9)、55.56%(5/9)和77.78%(7/9);12个月时为11.11%(1/9)、44.44%(4/9)、77.78%(7/9)和77.78%(7/9).生物力学显示6个月时,前屈、后伸、左屈和右屈的融合刚度:髂骨＞SF/CPC/rhBMP-2＞CPC/rhBMP-2＞SF/CPC;12个月时SF/CPC/rhBMP-2刚度与髂骨相近,SF/CPC最小.组织学定量表明:6个月时,髂骨新生骨量＞SF/CPC/rhBMP-2＞CPC/rhBMP-2＞SF/CPC;而钙磷残留量依次增多;12个月时,SF/CPC/rhBMP-2新生骨量与髂骨相近;SF/CPC最少;钙磷残留量依次增多.结论 SF/CPC/rhBMP-2人工骨具有骨传导和骨诱导性,降解与成骨能力匹配,是一种理想的脊柱融合材料.     

丝素蛋白增强型磷酸钙复合rhBMP-2用于绵羊腰椎椎体间融合的实验研究

目的 评价可注射丝素蛋白增强型磷酸钙(silk fibroin/calcium phosphate cement,SF/CPC)复合人重组骨形态发生蛋白-2(recombinant human bone morphogenetic protein-2,rhBMP-2)应用于绵羊腰椎椎体间融合的效果.方法 24只绵羊均建立L1.2、L3.4和L5.6前路椎体间融合模型.每只绵羊的3个腰椎间隙随机植入SF/CPC、CPC/rhBMP-2、SF/CPC/rhBMP-2和自体髂骨中的3种.分别于术后6个月和12个月各处死12只绵羊.每个时段均获得36个腰椎手术节段,每种材料9个节段.通过大体观察、手触检测、CT扫描、非破坏性生物力学测试和组织学观察分析脊柱融合状况.结果 术后6个月时,手触检测SF/CPC、CPC/rhBMP-2、SF/CPC/rhBMP-2以及髂骨的融合率分别为0、33.33%(3/9)、55.56%(5/9)和77.78%(7/9);12个月时为11.11%(1/9)、44.44%(4/9)、77.78%(7/9)和77.78%(7/9).生物力学显示6个月时,前屈、后伸、左屈和右屈的融合刚度:髂骨＞SF/CPC/rhBMP-2＞CPC/rhBMP-2＞SF/CPC;12个月时SF/CPC/rhBMP-2刚度与髂骨相近,SF/CPC最小.组织学定量表明:6个月时,髂骨新生骨量＞SF/CPC/rhBMP-2＞CPC/rhBMP-2＞SF/CPC;而钙磷残留量依次增多;12个月时,SF/CPC/rhBMP-2新生骨量与髂骨相近;SF/CPC最少;钙磷残留量依次增多.结论 SF/CPC/rhBMP-2人工骨具有骨传导和骨诱导性,降解与成骨能力匹配,是一种理想的脊柱融合材料.     

丝素蛋白/双相磷酸钙/半水硫酸钙/重组人骨形态发生蛋白-2骨水泥的制备及修复椎体骨缺损的实验研究

目的 研制丝素蛋白(SF)/双相磷酸钙(BCP)/半水硫酸钙(CSH)/重组人骨形态发生蛋白-2(rhBMP-2)骨水泥,并探讨其在绵羊椎体内的成骨作用. 方法 制备SF/BCP/CSH/rhBMP-2骨水泥,分别在12只绵羊的L2 L3、L4椎体内制作直径为6.0mm、深度为10 mm的圆柱型骨缺损模型,在3个缺损处随机植入SF/BCP/CSH/rhBMP-2骨水泥作为实验组,植入聚甲基丙烯酸甲酯(PMMP)作为对照组,另一椎体缺损处不植入任何材料作为空白对照组.术后3、6个月分别随机处死6只绵羊进行CT、组织学和生物力学检查.结果 CT和组织学检查显示:术后3个月实验组椎体密度与正常椎体相似,骨缺损修复基本完成,术后6个月骨缺损修复完成;对照组术后3、6个月时PMMP无降解,并与骨之间结合疏松,表面无新骨形成;空白对照组术后3、6个月时骨缺损一直存在.生物力学测试显示:术后3、6个月时实验组椎体抗压强度和刚度与正常椎体相比差异无统计学意义(P＞0.05). 结论 SF/BCP/CSH/rhBMP-2骨水泥具有良好的成骨作用,在成骨过程中能维持椎体的力学性能,有望成为经皮椎体强化术的一种可降解、具成骨作用的填充剂.     

rhBMP-2/CPC强化骨质疏松椎体力学强度的实验研究

目的观察人重组骨形态发生蛋白-2复合磷酸钙骨水泥(recombinant human bonemorphogenetic protein-2/calcium phosphate cement,rhBMP-2/CPC)强化骨质疏松绵羊腰椎生物力学强度的动态效果。方法成年雌性绵羊12只行去势手术后饲养1年,测量去势前后腰椎骨密度。取L1-L6为实验对象,空白组不给予任何处理;CPC组中,经椎弓根向椎体内注射CPC(2.0 ml);rhBMP-2/CPC组中,经椎弓根向椎体内注射rhBMP-2/CPC(2.0 ml)。于术后1天、6周、12周和24周四个时间点各随机处死3只绵羊,对椎体行压缩实验,分别测量各组中椎体的最大压缩应力(σult)和能量吸收值(EAV),对比分析同一时间点不同方法之间和同一方法的不同时间点之间的力学指标。结果去势1年后绵羊腰椎骨密度显著下降,差异有显著性(P<0.05),骨质疏松绵羊模型建立成功。在术后各时间点,CPC组和rhBMP-2/CPC组的σult和EAV均显著高于空白组(P<0.05);术后1天、6周和12周,rhBMP-2/CPC组和CPC组之间的差异无统计学意义(P>0.05),而rhBMP-2/CPC组中24周的σult显著高于CPC组(P<0.05)。空白组和CPC组中σult各时间点之间的差异均无显著性(P>0.05),而rhBMP-2/CPC组中24周的σult显著高于该组其他三个时间点(P<0.05)。结论 rhBMP-2/CPC不仅能提高骨质疏松椎体的即时强度,还能很好的维持椎体的动态力学强度和进一步提高椎体的远期强度,为脊柱达到坚强骨性融合提供了良好的力学环境。     

rhBMP-2/异体骨复合骨应用于兔腰椎植骨融合的实验研究

目的评价rhBMP-2/异体骨复合骨在兔腰椎后路横突间植骨融合中的效果,探讨此复合骨替代自体骨用于腰椎后路横突间植骨融合的可能性。方法30只新西兰大白兔随机分为三组,行后路腰椎横突间植骨融合术,分别植入自体髂骨条、rhBMP-2/异体骨复合骨及单纯异体髂骨条。术后喂养6周,处死动物,取出标本,分别采取盲法进行手工测试,影像学、组织学观察及单向拉伸的生物力学测试,并用图像分析系统定量分析植骨区内成骨量,取得数据后进行综合评价。结果手工测试显示rhBMP-2/异体骨复合骨组融合率(90%)明显优于自体骨(40%)及异体骨组(20%)(P＜0．05)。影像学及组织学显示rhBMP-2/异体骨复合骨组成骨速度及骨成熟程度均优于其它两组。单向拉伸生物力学测试结果表明复合骨组和自体骨组两组间无明显差别(P＞0．05),但均明显优于异体骨组(P＜0．05)。定量分析显示植骨区内新骨形成面积复合骨组和自体骨组两组间无明显差别(P＞0．05),但均明显优于异体骨组(P＜0．05)。结论在兔腰椎后路横突间植骨融合术中,rhBMP-2/异体骨复合骨可促进骨形成并提高融合率,可作为替代自体骨的理想材料。     

rhBMP-2复合物与自体骨移植后腰椎融合率的系统评价

目的分析比较rhBMP-2复合物与自体髂骨移植后植骨融合率的差异。方法检索Cochrane liabrary（CCTR）以及Cochrane协作网专业试验数据库，MEDLINE（1966～2006），EMBASE（1980～2006），PUBMED（1966～2006），NRR（http：//www．update-software．com／National），CCT（http：//www．controlled-trials．com）。收集了有关rhBMP-2复合物与自体髂骨应用于腰椎手术的临床随机对照试验。统计软件采用Cochrane协作网提供的RevMan4．2．9。结果共纳入有关rhBMP-2复合物与自体髂骨应用于脊柱手术中的临床随机对照试验4篇共364例患者。Meta分析表明，rhBMP12复合物对比自体髂骨在治疗腰椎疾病的手术当中，术后6个月、12个月及24个月的植骨融合率明显高于自体髂骨。结论rhBMP-2复合物用于腰椎疾病的手术治疗时，其中、远期植骨融合率的效果明显优于自体髂骨。     

多孔载因子CPC促进骨缺损愈合的实验研究

[目的]探讨磷酸钙骨水泥复合rhBMP-2/明胶微球复合材料在治疗骨缺损时的降解、成骨性能。[方法]制备携载rhBMP-2的明胶微球(GMs),与磷酸钙骨水泥(CPC)复合,制备出rhBMP-2/GMs/CPC复合人工骨。取30只新西兰大白兔,在前臂桡骨中段制造人工骨缺损,随机分成3组,分别植入rhBMP-2/GMs/CPC/复合物(A组)、GMs/CPC(B组)、rhBMP-2/CPC(C组),术后6、12周分别进行X线检测、骨密度测定,术后12周处死动物,分别行生物力学测定,脱钙切片、HE染色,不脱钙切片进行荧光显微镜下观察双标间距,计算平均矿化率。[结果]与GMs/CPC、rhBMP-2/CPC组比较,复合材料植入后不同时间点的材料降解及成骨均高于对照组。12周A组标本生物力学实验测定结果表明指标接近正常,与B、C组比较有统计学差异。骨密度12周、新骨矿化率提示有统计学差异。[结论]rhBMP-2/GMs/CPC微球系统复合材料在体内易降解,具有良好成骨活性,是良好的骨修复材料。     

负载rhBMP-2的CPC活性人工骨修复骨缺损的临床应用

目的 探讨负载rhBMP-2的CPC活性人工骨修复骨缺损的临床应用,评价其临床使用效果和安全性.方法 2006年6月-2007年9月,采用负载rhBMP-2的CPC(rhBMP-2/CPC组)和单纯CPC(对照组)修复骨缺损112例,骨缺损范围为1 cm×1 cm×1 cm～4 cm×3 cm×3 cm.其中对照组63例,男31例,女32例;年龄17～70岁,平均47.4岁.骨缺损部位:跟骨19例,胫骨平台20例,肱骨近端8例,桡骨远端9例,胸腰椎7例.rhBMP-2/CPC组49例,男31例,女18例;年龄16～68岁,平均45.6岁.骨缺损部位:跟骨11例,胫骨平台16例,肱骨近端7例,桡骨远端2例,胫骨远端2例,胸腰椎11例.术中采用负载rhBMP-2/CPC(2～5 g)或单纯CPC(2～50 g)填充骨缺损.结果 术后108例伤口Ⅰ期愈合;术后2周对照组1例及rhBMP-2/CPC组3例伤口有淡黄色清亮稀薄分泌物渗出,经换药及激素治疗后愈合.所有患者未见毒性反应,无皮疹或高热,肝肾功能、血、尿常规及C反应蛋白均正常.112例均获随访,随访时间12～24个月,平均13.2个月.随访期间未发生骨髓炎,无再骨折,无明显骨缺损修复后再塌陷,无钢板及螺钉松动、断裂等并发症,脊柱手术的椎体前缘无高度不足发生.两组术后3个月骨折均达骨性愈合,无延迟愈合或骨不连发生.患肢活动情况良好,屈伸功能达正常活动水平.结论 负载rhBMP-2的CPC活性人工骨修复骨缺损安全、有效,是一种理想的骨缺损修复材料.     

不同充填材料应用于山羊经皮椎体成形术的组织学研究

目的:研究聚甲基丙烯酸甲酯(PMMA)、磷酸钙人工骨(CPC)和复合重组人骨形态发生蛋白-2的磷酸钙人工骨(rhBMP-2/CPC)在山羊骨质疏松症模型上行经皮椎体成形术(PVP)后的组织学表现。方法:6～8岁雌性山羊8只,均行双侧卵巢切除术,术后4个月建立骨质疏松症模型。在C形臂X线机监视下,随机选取8只山羊的L2-L6的两节椎体行PVP,分别充填PMMA、CPC和rhBMP-2/CPC,保证每只山羊的两节穿刺椎体的充填材料各不相同,术后4个月处死所有动物,取出椎体,组织学观察。结果:8只山羊16个椎体的PVP均成功,共出现4个椎体的渗漏。肉眼观察:PMMA与松质骨界限清晰,一个椎体取材时交界面出现破碎和脱落现象;而CPC和rhBMP-2/CPC与椎体内松质骨界限不清,互相融合生长。HE染色光镜观察:PMMA与骨小梁松散结合,界限明显,未见PMMA吸收和新生骨形成;CPC均匀分布于骨小梁和骨髓组织内,有CPC吸收现象,同时可见有新生软骨样团块形成,并有新生骨组织形成向其中心长入;rhBMP-2/CPC除了CPC的表现外,可见成骨活动活跃。结论:在组织学上,rhBMP-2/CPC和CPC均具有降解活性和骨传导活性,优于PMMA。rhBMP-2/CPC还具有诱导成骨活性,可能成为PVP中强化骨质疏松性椎体的首选充填材料。     

组织工程复合骨移植材料椎体间脊柱融合实验研究

目的:观察组织工程复合骨移植材料在兔腰椎椎体间脊柱融合的愈合情况。方法:自体骨髓基质细胞体外培养,诱导分化为成骨细胞,种植到多孔钙磷陶瓷载体中,体外旋转细胞培养构建成组织工程复合骨移植材料。实验分为5组:假手术组、空载体组、自体髂骨组、旋转培养复合体组和rhBMP-2复合体组。椎体间移植12周后,通过大体观察、手法检测、影像学、生物力学和组织学方法评价脊柱融合愈合情况。结果:假手术组不能自行达到脊柱融合;空载体移植组脊柱融合率为50%;自体髂骨移植组为66.7%;旋转培养复合体组和rhBMP-2复合体移植组为100%,融合块较大,生物力学强度高。结论:旋转细胞培养方法构建的骨髓基质来源的成骨细胞-钙磷陶瓷复合骨移植材料椎体间脊柱融合率优于自体髂骨移植,可以替代自体髂骨进行椎体间脊柱融合;复合骨移植材料中结合骨生长因子rhBMP-2能够进一步加强脊柱融合的生物力学强度。     

Biological performance of a polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model

Purpose

We develop a sheep thoracic spine interbody fusion model to study the suitability of polycaprolactone-based scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within the thoracic spine. The surgical approach is a mini-open thoracotomy with relevance to minimally invasive deformity correction surgery for adolescent idiopathic scoliosis. To date there are no studies examining the use of this biodegradable implant in combination with biologics in a sheep thoracic spine model.

Methods

In the present study, six sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels: (a) calcium phosphate (CaP) coated polycaprolactone-based scaffold plus 0.54 μg rhBMP-2 (b) CaP-coated PCL-based scaffold alone or (c) autograft (mulched rib head). Fusion was assessed at 6 months post-surgery.

Results

Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL-based scaffold group in comparison with either PCL-based scaffold alone or autograft. These results were supported by histological evaluations of the respective groups. Biomechanical testing revealed significantly higher stiffness for the rhBMP-2 plus PCL-based scaffold group in all loading directions in comparison with the other two groups.

Conclusion

The results of this study demonstrate that rhBMP-2 plus PCL-based scaffold is a viable bone graft substitute, providing an optimal environment for thoracic interbody spinal fusion in a large animal model.     

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.     

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.     

重组人骨形态发生蛋白-2/异体骨复合骨用于兔腰椎融合的显微CT研究

目的 观察重组人骨形态发生蛋白-2/异体骨复合骨、自体骨与异体骨分别用于兔腰椎融合后,不同时间点融合骨组织微结构的变化.方法 成年雄性新西兰大白兔45只,随机分为3组,每组15只.在每只兔的L5、L6横突间行腰椎后路植骨融合术,各组分别植入复合骨条,自体髂骨条以及单纯异体髂骨条,每组于术后第3、4、5周各处死5只大白兔,分离保存融合节段标本.用显微cT扫描后行骨组织定量分析.结果 术后3个时间点中,复合骨组和自体骨组新生骨小梁的强度和形态均要优于异体骨组且差异有统计学意义(P＜0.05).第3周,复合骨组的组织骨密度(TMD)为(433.98±2.64)mg/cm3,高于自体骨组(424.81±4.69)mg/cm3(P＜0.05);第4周,复合骨组的骨小梁厚度(Tb.Th)为(0.097±0.004)mm,高于自体骨组(0.082±0.003)mm(P＜0.01);第5周,复合组的组织矿含量(TMC)为(7.70±0.30)mg,高于自体骨组(7.00±0.24)mg(P＜0.01).结论 在兔腰椎后路横突间植骨融合中,重组人骨形态发生蛋-2/异体骨复合骨的成骨效应不低于自体骨,优于异体骨.     

Differences in early osteogenesis and bone micro-architecture in anterior lumbar interbody fusion with rhBMP-2, equine bone protein extract,and autograft

PurposeTo investigate the microstructural differences and responsible mechanisms in early bone formation in anterior lumbar interbody fusion (ALIF) in the spine using rhBMP-2 (INFUSE), equine bone protein extract (COLLOSS E) or autograft.MethodsTwelve Danish female landrace pigs underwent a 3-level ALIF procedure at L3–6. PEEK interbody cages packed with rhBMP-2, COLLOSS E, or autograft were inserted. The animals were divided into two groups of six, and observed for four and eight weeks postoperatively. μCT was performed for evaluation of microstructure of the bone within the cage. A mathematical finite element model was developed to investigate the aqueous behavior within the cages when exposed to external compressive forces.ResultsAt 4 weeks postoperative bone surface volume fraction (BS/TV) using rhBMP-2 was higher than with use of COLLOSS E and autograft, while trabecular thickness (Tb.Th.) was lower using rhBMP-2 at this time-point. At eight weeks BS/TV and trabecular number (Tb.N.) were still higher using rhBMP-2 than autograft and COLLOSS E. Connectivity density was significantly higher using rhBMP-2 than using autograft or COLLOSS E at both time-points. Between four- and eight-week time-points BV/TV and Tb.Th. rose while Tb.N. declined using rhBMP-2. The degree of anisotropy and the calculated amount of trabeculae with main direction along the spinal axis, were higher at four weeks using COLLOSS E. rhBMP-2 had the highest amount of trabeculae directed along the spinal axis at eight weeks. A change in main direction between four and eight weeks was observed for both autograft and rhBMP-2. The numerical results from the finite element model verify that significantly different flow pattern emerges as the boundary conditions are altered. At four weeks there was an evident correlation between trabecular orientation and flow pattern using rhBMP-2.ConclusionThis study reveals large differences in microstructure in the early osteogenesis and explains important mechanisms of early bone formation using rhBMP-2, COLLOSS E or autograft treatment. These differences might explain some of the unfortunate events reported such as edema, swelling, and excessive bone formation using different bone graft substitutes in spinal fusion procedures.     

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。     

重组人骨形态发生蛋白-2/异体骨复合骨用于兔腰椎融合的正电子发射计算机体层摄影-CT研究

目的 通过应用正电子发射计算机体层摄影-CT(PET-CT)研究重组人骨形态发生蛋白-2(rhBMP-2)/异体骨复合骨行兔腰椎融合术后不同时间点融合骨组织再血管化程度及成骨活性的变化.方法 成年雄性新西兰大白兔45只,随机分为3组,每组15只.在每只兔的L4、L5横突间行腰椎后路植骨融合术,3组分别植入rhBMP-2/异体骨复合骨条(复合骨组)、自体髂骨条(白体骨组)及异体髂骨条(异体骨组),每组于术后2、4、6周注射18F-NaF,利用PET-CT对各组动物进行全身显像,对比各组植骨区摄取值(SUV).结果 2、4、6周时复合骨组和白体骨组植骨区对18F-NaF的SUV均优于异体骨组,差异有统计学意义(P＜0.05);复合骨组植骨区的SUV在4、6周时高于自体骨组,差异有统计学意义(P＜0.05),2周时与自体骨组差异无统计学意义(P＞0.05).同一组内不同时间点复合骨组和白体骨组均在4、6周时局部SUV高于2周时,差异有统计学意义(P＜0.05);4周与6 周之间差异无统计学意义(P＞0.05).异体骨组的SUV 3个时间点问差异均无统计学意义(P＞0.05).结论 兔腰椎后路植骨融合术中PET-CT检测显示:rhBMP-2/异体骨复合骨可促进骨形成并改善局部血液供应,可作为替代自体骨的理想材料.     

Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages

In a multicenter, prospective, randomized, nonblinded, 2-year study, 279 patients with degenerative lumbar disc disease were randomly divided into two groups that underwent interbody fusion using two tapered threaded fusion cages. The investigational group (143 patients) received rhBMP-2 on an absorbable collagen sponge, and a control group (136 patients) received autogenous iliac crest bone graft. Plain radiographs and computed tomographic scans were used to evaluate fusion at 6, 12, and 24 months after surgery. Mean operative time (1.6 hours) and blood loss (109.8 mL) were less in the investigational rhBMP-2 group than in the autograft control group (2.0 hours and 153.1 mL). At 24 months the investigational group's fusion rate (94.5%) remained higher than that of the control group (88.7%). New bone formation occurred in all investigational patients. At all intervals, mean postoperative Oswestry, back pain, and leg pain scores and neurologic status improved in both treatment groups with similar outcomes. In the control group, eight adverse events related to the iliac crest graft harvest occurred (5.9%), and at 24 months 32% of patients reported graft site discomfort and 16% were bothered by its appearance. Lumbar fusion using rhBMP-2 and a tapered titanium fusion cage can yield a solid union and eliminate the need for harvesting iliac crest bone graft.