复合重组人骨形态发生蛋白-2的可注射磷酸钙骨水泥在椎体成形术中的生物力学研究

目的探讨自主研发的复合重组人骨形态发生蛋白-2（rhBMP-2）的可注射磷酸钙骨水泥（CPC）应用于猕猴椎体成形术早期和后期生物力学性能。方法①将2只成年猕猴尸体作为I组，4只成年猕猴分为Ⅱ、Ⅲ两组，每组猕猴T10-L7的20个椎体分为A、B、C三组，经皮穿刺。A组：8个椎体，灌注复合rhBMP-2的可注射CPC；B组：6个椎体，灌注注射型PMMA；C组：6个椎体，手术空白对照组，穿刺后灌注生理盐水。②I组于术后立即进行测试，Ⅱ、Ⅲ组分别于术后2个月和6个月处死，解剖出单个椎体制成标本，在轴向压缩载荷下测定单个椎体的抗压强度和刚度。分析两种材料强化椎体的早期和后期效果及变化。结果C组椎体抗压强度和刚度于术后、术后2个月和6个月比较差异无统计学意义（P〉0．05）。A组椎体的抗压强度比C组椎体增加了29．1％（P〈0．05），术后2个月变为25．5％（P〈0．05），术后6个月与C组差异无统计学意义（P〉0．05）；抗压强度随时间逐渐下降（P均〈0．05），刚度始终无明显增高（P〉0．05）。B组椎体的抗压强度和刚度分别增加了55．2％和22．8％（P均〈0．05），2个月后变为52．7％和25．9％（P均〈0．05），6个月后仍增强48．6％和28．7％（P均〈0．05）。结论复合rhBMP-2的CPC材料强化椎体的力学性能良好并能始终维持适中的力学强度，可避免PMMA过高强度带来的远期邻近椎体骨折和椎间盘退行性变加速的危险。     

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。     

磷酸钙骨水泥在椎体成形术中的实验研究

目的 :模仿椎体成形术观察磷酸钙骨水泥 /聚甲基丙烯酸甲酯植入椎体后与椎体界面间的组织学差异。方法 :将PMMA和CPC植入到犬椎体 ,通过X线、CT、光镜、扫描电镜观察 2种材料与椎体界面间的微观结构变化。结果 :PMMA与椎体之间的结合是单纯的机械连接未能达到生物机械固定 ,CPC与骨界面间无排异反应的表现 ,是直接的骨小梁与生物材料之间的生物连接。结论 :磷酸钙骨水泥是椎体成形术中的一种比较理想的替代材料     

可注射硫酸钙基人工骨在羊股骨缺损植骨中的实验研究

[目的]通过可注射性植骨材料在羊股骨缺损的骨内植入,评价可注射硫酸钙基植骨材料的骨修复能力.[方法]建立绵羊单侧股骨缺损模型,将可注射硫酸钙基人工骨植入骨缺损内,于术后4、8、12周行大体观察及X线片检查缺损区骨痂生长情况.[结果]术后4周时材料大部分降解吸收,可见新生骨小梁结构,缺损区有部分骨痂形成;8周时可见大量新生骨小梁结构,部分形成成熟骨单位,可见骨母细胞,新生骨与宿主骨界面模糊,完成断端间的骨性桥接;12周时材料完全降解,形成的新生骨小梁部分出现重塑形成正常骨结构,缺损区被新骨完全替代,骨痂开始塑形,髓腔再通.[结论]可注射硫酸钙基人工骨作为骨移植替代材料,具有良好的骨传导性和骨诱导性,用于修复骨缺损可以取得良好的效果.     

注射型磷酸钙骨水泥在椎体成形术中的组织学研究

目的 模仿椎体成形术观察注射型磷酸钙骨水泥(CPC)／聚甲基丙烯酸甲（polymethylmethacrylate，PMMA)植入椎体后的微观结构变化。方法 将PMMA和CPC植入到犬椎体，通过X线、CT、光镜、扫描电镜观察二种材料与椎体界面间的微观结构变化。结果 PMMA与椎体之间的结合是单纯的机械连接未能达到生物机械固定，CPC与骨界面间无排异反应的表现，是直接的骨小梁与生物材料之间的生物连接，CPC与椎体之间的结合是生物连接可达到生物机械固定的目的。结论 磷酸钙骨水泥是椎体成形术中治疗胸腰椎爆裂骨折一种比较理想的材料。     

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.     

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.     

三种充填材料应用于山羊经皮椎体成形术的组织学评价

经皮椎体成形术（PVP）充填材料性能的优劣直接关系到PVP的成败，我们在山羊骨质疏松症（OP）模型上行PVP．充填聚甲基丙烯酸甲酯（PMMA）、可注射型的自固化磷酸钙人工骨（CPC）和复合重组人类骨形态发生蛋白-2（rhBMP-2）的CPC（rhBMP-2／CPC）三种材料。并行光镜观察，为寻找理想的PVP充填材料提供组织学依据。     

复合重组人类骨形态发生蛋白-2的磷酸钙骨水泥应用于椎体成形术的体外生物力学评价

目的 通过将复合重组人类骨形态发生蛋白-2的注射型磷酸钙人工骨(rhBMP-2/CPC)应用于体外经皮椎体成形术(PVP),评价其生物力学性能.方法 5具完整老年脊柱标本(T10～L2),游离成30个椎体,随机分为3组:I组为空白对照组(n=10);Ⅱ组为PMMA组(n=10);Ⅲ组为rhBMP-2/CPC组(n=10).G形臂监视下,Ⅱ、Ⅲ组经双侧椎弓根分别充填PMMA及BMP-2/CPC 5 ml,注射后摄轴位X线片了解骨水泥分布情况,测试3组椎体静态压缩下的最大抗压强度及刚度.结果 平均最大载荷和刚度分别为:I组:(1595.6±165.0)N和(934.8±120.2)N/mm;Ⅱ组:(3025.4±210.2)N和(1570.7±190.0)N/mm;Ⅲ组:(2778.8±156.5)N和(1361.9±230.5)N/mm;最大载荷:I～Ⅲ组之间均差异有统计学意义(P＜0.05).刚度:I～Ⅲ组之间差异有统计学意义(P＜0.05).结论 rhBMP-2/CPC可以恢复骨质疏松椎体的力学性能.     

Biomechanical evaluation of kyphoplasty and vertebroplasty with calcium phosphate cement in a simulated osteoporotic compression fracture

 Kyphoplasty and vertebroplasty with polymethylmethacrylate (PMMA) have been used for the treatment of osteoporotic vertebral compression fractures. We performed kyphoplasty and vertebroplasty with α-tricalcium phosphate cement (CPC) and PMMA to compare the biomechanical properties. Thirty osteoporotic vertebrae were harvested from nine embalmed cadavers. We randomized the vertebrae into four treatment groups: (1) kyphoplasty with CPC; (2) kyphoplasty with PMMA; (3) vertebroplasty with CPC; and (4) vertebroplasty with PMMA. Prior to injecting the cement, all vertebrae were compressed to determine their initial strength and stiffness. They were then recompressed to determine their augmented strength and stiffness. Although the augmented strength was greater than the initial strength in all groups, there was no significant difference between the two bone cements for either kyphoplasty or vertebroplasty. The augmented stiffness was significantly less than the initial stiffness in the kyphoplasty groups, but the difference between the two cements did not reach significance. In the vertebroplasty groups, the augmented stiffness was not significantly different from the initial stiffness. There was no significant difference between the two bone cements for either procedure when cement volume and restoration of anterior height were assessed. We concluded that kyphoplasty and vertebroplasty with CPC were viable treatment alternatives to PMMA for osteoporotic vertebral compression fractures. Received: July 18, 2002 / Accepted: November 6, 2002 Offprint requests to: S. Tomita     

新型纳米级rhBMP-2磷酸钙骨水泥修复股骨假体翻修时骨缺损的组织学研究

目的探讨新型纳米级复合人类基因重组骨形态发生蛋白-2（rhBMP-2）／磷酸钙骨水泥（CPC），合称CCPC，在修复股骨假体翻修时骨缺损的成骨作用。方法选择8只健康成年杂种犬，每只犬双侧股骨通过配对，均进行人工股骨头置换手术，一侧为实验组，即CCPC组；另一侧为对照组，即同种异体颗粒性松质骨组（MCA组）。术中按临床上AAOS分型Ⅱ型Ⅱ度行股骨近端骨缺损造模，然后分别应用CCPC和MCA两种材料填充股骨近端骨缺损区，同时固定股骨假体。术后3、6个月分别取出各组骨缺损区标本进行大体及组织学切片观察，了解骨缺损的修复情况。结果术后3个月CCPC组与MCA组骨缺损区均见有新骨形成，术后6个月两种植入材料基本被吸收替代，骨一材料结合良好，骨缺损修复良好。结论纳米级复合rhBMP-2／CPC的骨缺损修复能力与MCA相似。     

Vertebroplasty comparing injectable calcium phosphate cement compared with polymethylmethacrylate in a unique canine vertebral body large defect model.

BACKGROUND CONTEXT: Vertebroplasty was developed to mechanically reinforce weakened vertebral bodies. Polymethylmethacrylate (PMMA) bone cement has been most commonly used but carries risks of thermal injury and respiratory and cardiovascular complications. Calcium phosphate (CaP) offers the potential for biological resorption and replacement with new bone, restoring vertebral body mass and height. PURPOSE: To compare compressive strength, elastic modulus of the adjacent motion segments, and histologic response of vertebral bodies injected with either CaP or PMMA in a canine vertebroplasty model. STUDY DESIGN: By using a canine vertebroplasty model, two level vertebroplasties were performed at L1 and L3 and studied for 1 month (n=10) and 6 months (n=10). In each canine, one vertebral defect was randomly injected with either CaP cement (BoneSource; Stryker, Freiberg, Germany) or PMMA. METHODS: Twenty dogs had an iatrogenically created cavitary lesion at two nonadjacent levels injected with either CaP or PMMA. Canines from each group were tested mechanically (n=5) and histologically (n=5). Histology consisted of axial sections of the L1 and L3 vertebral bodies and high-resolution contact radiographs. Sections from each specimen were embedded in plastic without decalcification to study the bone-cement interface. Bone-cement interfaces were compared for evidence of necrosis, fibrosis, foreign body response, cement resorption, and new bone formation between the PMMA and CaP treatments groups. Mechanical compression testing was performed on specimens from the 1-month (n=5) and 6-month (n=5) time periods. The T13 vertebral body was used as an intact control for the destructive compression testing of L1 and L3. Each vertebral body was compressed to 50% of its original height under displacement control at 15 mm/min to simulate a nontraumatic loading situation. Force and displacement data were recorded in real time. RESULTS: Vertebral sites containing PMMA were characterized by a thin fibrous membrane. PMMA was detected within the trabeculae, vascular channels, and the spinal canal. Unlike PMMA, CaP underwent resorption and remodeling with vascular invasion and bone ingrowth. Woven and lamellar bone was found on the CaP cement surface, within the remodeled material, and on the surrounding trabeculae. Vertebral body compression strength testing revealed no significant difference in vertebral body height and compressive strength between PMMA and CaP. There was a trend for CaP-treated vertebrae to increase in compressive strength from 1 month to 6 months, whereas PMMA decreased compressive strength when compared with adjacent nontreated vertebrae. CONCLUSION: For both short and intermediate time periods, the injection of CaP cement can be an effective method to treat large vertebral defects. Early results indicate that CaP remodeling might result in the resorption of the majority of the cement with replacement by lamellar bone.     

Biomechanical evaluation of vertebroplasty using calcium sulfate cement for thoracolumbar burst fractures

OBJECTIVE: To evaluate the biomechanical performance of vertebroplasty using calcium sulfate cement for thoracolumbar burst fractures. METHODS: Sixteen bovine thoracolumbar spines (T11-L1) were divided into 4 groups (A,B,C and D). After burst-fracture model was created, 12 vertebral bodies in Groups A, B and C were augmented with calcium sulfate cement (CSC), calcium phosphate cement (CPC) and polymethylmethacrylate (PMMA) bone cement, respectively. Each anterior vertebral body height was measured with a caliper at 4 time points: intact conditions (HInt), post-fracture (HFr), post-reduction (HRe) and post-vertebroplasty (HVP). The filling volume of 3 different bone cements was also measured. Each vertebral body was compressed at 0.5 mm/s using a hinged plating system on a materials testing machine to 50% of the post-vertebroplasty height to determine strength and stiffness. Difference was checked using t test or One-way ANOVA. RESULTS: The average strike energy was 66.2 J. Vertebroplasty with different cements could sustain vertebral height.The average filling volume of bone cement in 3 groups was 4.35 ml (CSC), 3.72 ml (CPC) and 3.95 ml (PMMA), respectively, and there was no statistically significant difference among them (P larger than 0.05). Vertebroplasty with PMMA completely restored strength (116%) and stiffness (105%). CSC or CPC partly recovered vertebral strength and stiffness. However, greater strength restoration was got with CSC (1659 N) as compared with CPC (1011N, P less than 0.01). Regarding stiffness, differences between CSC (140 N/mm+/-40 N/mm)and the other two bone cements (CPC:148 N/mm+/-33 N/mm, PMMA:236 N/mm+/-97 N/mm) were not significant (P larger than 0.05). CONCLUSIONS: For a burst-fracture of calf spine, use of CSC for vertebroplasty yields similar vertebral stiffness as compared with PMMA or CPC. Although augmentation with CSC partly obtains the normal strength, this treatment still can be applied in thoracolumbar burst fractures with other instrumental devices in light of its bioactivation.