bBMP/胶原/珊瑚复合人工骨修复股骨头骨缺损的实验研究

目的　研究用复合人工骨治疗股骨头坏死的效果。方法　建立双侧股骨头内骨缺损模型 ,并分为 4组 :bBMP/胶原 /珊瑚复合人工骨组 (6侧 )、肌骨瓣组 (6侧 )、单纯珊瑚组 (2例 )、对照组 (14例 ) ,为上各组的对侧。对植入后 3周、 16周的股骨头行病理学检查、计量组织学分析及四环素荧火标记。结果　 16周后 ,复合人工骨的骨缺损大小、缺损区骨小梁体积、荧光带宽度均与对照组有统计学显著性 ,但 5侧中有 1侧出现继发性骨关节炎。结论　该复合人工骨有较强的传导成骨及诱导成骨作用 ,是修复股骨头骨缺损的良好移植材料 ,但它不能改善缺血坏死股骨头的血供。该股骨头内骨缺损加用 95 %酒精灌注 ,模型近似于股骨头坏死囊性变 ,对于研究股骨头坏死的治疗有较大价值     

bBMP／胶原／珊瑚复合人工骨修复股骨头骨缺损的实？…

目的 研究用复合人工骨治疗骨头坏死的效果。方法 建立双侧股骨头内骨缺损模型，并分为４组：ｂＢＭＰ／胶原／珊瑚复合人工骨组（６０侧）、肌骨瓣组（６侧）、单纯珊瑚组（２例）、对照组（１４例），为上各组的对侧。对主后３周、１６周的股骨头行病理学检查、计量组织学分析及四环素荧火标记。结果 １６周后，复合人工骨的骨缺损大小、缺损区骨小梁体积、荧光带宽度均与对照组有统计学显著性，但５侧中有１侧出现继发性骨关节     

bBMP—胶原—珊瑚复合人工骨修复桡骨干骨缺损的实验研究

目的 评价牛骨形态发生蛋白（bBMP）－胶原－珊瑚复合人工骨对长骨干骨缺损的修复效果。方法 建立46只兔双侧桡骨干骨缺损模型,分为4组：1．人工骨组（18侧）、2．自体骨组（16侧）、3．单纯珊瑚组（12侧）、4．对照组（为以上各组的左侧,未治疗）。于4周及16周未分别行X线、病理学、ALP活性、四环素荧光标记及生物力学检查。结果 4周,人工骨组组织中的ALP活性高于对照组。16周,1、2、3、4组的愈合率,分别为75％（9／12）、100％（10／10）、28．6％（2／6）、31．0％（9／29）。与3组及4组相比,1组及2组的荧光带较宽,桡骨的抗弯强度较高。结论 复合人工骨有较强的修复长骨干骨缺损的能力,有望成为自体骨的替代品。     

带血运骨-软骨复合移植的实验研究

目的 比较带血运与不带血动骨－软骨复合移植的成活质量。方法 １４只犬分成２组,每组７只,分别做带血运及不带血运第二拓骨头移植,修复股骨头局限性骨－软骨缺损,术后１２周行光镜、电镜及同位素＾９９ｍＴＣ－ＭＤＰ检测。结果 带血运移植的第二跖骨头于术后１２周仍然保持了基本正常的软骨组织结构形态,而不带血运移植组出现了明显的软骨变性及破坏。结论 带血运骨－软骨复合移植修复受区局限性软骨缺损可获得良好效果．     

实验性股骨头骨缺损修复过程的生物力学研究

目的及方法：本实验分脱位组、未脱位组及正常组，对犬股骨头内骨缺损修复过程进行计量组织学及生物力学的研究。结果：脱位组股骨头均塌陷，未脱位组囊腔硬化带形成，两组囊腔均未完全闭合。脱位组的骨小梁体积及软骨下骨厚度较正常组及未脱位组低。脱位组松质骨的抗压强度及弹性模量较未脱位组低，未脱位组在三组中最高。脱位组的软骨下骨的生物力学特性较正常组及未脱位组低。结论：股骨头脱位可致股骨头坏死塌陷，股骨头塌陷与软骨下骨的生物力学特性及厚度有关，后两者间亦存在相关关系。囊腔硬化带形成是种代偿反应，但可产生应力遮挡，不利于囊腔的闭合。此模型，可用于研究移植等对股骨头坏死修复的效果。     

实验性股骨头骨缺损修复过程的生物力学研究

目的及方法　本实验分脱位组、未脱位组及正常组 ,对犬股骨头内骨缺损修复过程进行计量组织学及生物力学的研究。结果　脱位组股骨头均塌陷 ,未脱位组囊腔硬化带形成 ,两组囊腔均未完全闭合。脱位组的骨小梁体积及软骨下骨厚度较正常组及未脱位组低。脱位组松质骨的抗压强度及弹性模量较未脱位组低 ,未脱位组在三组中最高。脱位组的软骨下骨的生物力学特性较正常组及未脱位组低。结论　股骨头脱位可致股骨头坏死塌陷 ,股骨头塌陷与软骨下骨的生物力学特性及厚度有关 ,后两者间亦存在相关关系。囊腔硬化带形成是种代偿反应 ,但可产生应力遮挡 ,不利于囊腔的闭合。此模型 ,可用于研究移植等对股骨头坏死修复的效果。     

bBMP-胶原-珊瑚复合人工骨修复桡骨干骨缺损的实验研究

目的评价牛骨形态发生蛋白(bBMP)-胶原-珊瑚复合人工骨对长骨干骨缺损的修复效果.方法建立46只兔双侧桡骨干骨缺损模型,分为4组1.人工骨组(18侧)、2.自体骨组(16侧)、3.单纯珊瑚组(12侧)、4.对照组(为以上各组的左侧,未治疗).于4周及16周末分别行X线、病理学、ALP活性、四环素荧光标记及生物力学检查.结果4周,人工骨组组织中的ALP活性高于对照组.16周,1、2、3、4组的愈合率,分别为75%(9/12)、100%(10/10)、28.6%(2/7)、31.0%(9/29).与3组及4组相比,1组及2组的荧光带较宽,桡骨的抗弯强度较高.结论复合人工骨有较强的修复长骨干骨缺损的能力,有望成为自体骨的替代品.     

实验性股骨颈骨折修复过程的生物力学研究

目的：探索股骨颈骨折引起股骨头坏死塌陷的发病机理。方法：在犬股骨头颈交界处截断股骨颈,术后分5周组（5条）。20周组（5条）及各组的对照组,对其修复过程进行病理学,计量组织学、四环素标记及生物力学的研究。结果：（1）病理学检查：5周组,股骨头内骨小梁坏死,其框架结构不变;20周组,股骨头关节面塌陷,头内纤维组织、软骨痂及骨痂形成。（2）计量组织学分析示20周组的股骨头骨小梁体积及软骨下骨厚度较对照组及5周组低。（3）四环素标记示20周组的荧光带比对照组及5周组宽。5周组的最窄。（4）生物力学测定：20周组的软骨下骨及松质骨的生物力学强度较对照组及5周组低。结论：股骨颈骨折可致股骨头坏死,后者引起修复及血供重建,修复则可导致塌陷,股骨头塌陷与软骨下骨及松质骨的生物力学特性关系密切。     

组织工程方法修复羊腭裂骨缺损的初步研究

目的对羊骨髓基质干细胞（Bone marrow stromal cells，BMSCs）复合珊瑚修复腭裂骨缺损的可行性进行初步探讨。方法体外培养扩增、成骨诱导羊BMSCs。将第3代细胞复合珊瑚修复羊完全性腭裂骨缺损，以单纯珊瑚植入缺损作为对照组。术后16周头颅CT扫描、大体观察、评价骨缺损的修复效果。结果三维CT显示，实验组可见珊瑚被新生骨替代，对照组可见珊瑚明显降解，裂隙仍然存在。大体观察显示实验组骨缺损基本愈合；对照组中珊瑚明显降解，裂隙仍然存在。结论初步证明羊BMSCs成骨诱导后与珊瑚复合能修复羊腭裂骨缺损。     

异种脱蛋白骨管移植修复大段骨缺损的力学评估

目的研究异种脱蛋白骨管移植修复大段骨缺损的生物力学变化。方法建立山羊双侧胫骨大段骨缺损模型,36只山羊(72只后肢)随机分为2组,实验组:异种脱蛋白骨管;对照组:异种脱蛋白骨粒;两组均在移植骨中添加了骨形态发生蛋白(BMP),并采用骨板、钢板双重固定修复骨缺损。术后5、10、15周对羊胫骨行影像学观察和生物力学的变化。结果影像学显示实验组在骨缺损修复及成骨方面较对照组高。生物力学测试结果表明,术后5、10、15周时实验组力学强度较对照组明显增高,差异有统计学意义(P<0.05);术后15周,实验组的生物力学强度与正常胫骨已无差异。结论应用异种脱蛋白骨管支撑复合BMP修复大段骨缺损,能够有效加强移植骨修复负重骨缺损区的力学结构。     

带蒂大转子骨瓣修复股骨头生物力学研究

目的探讨带血管蒂大转子骨瓣转移治疗股骨头缺血性坏死的生物力学特点。方法比格犬22只,8—12个月龄,雌、雄各11例,体重7—10kg;分为3组,A组2只（4髋）作为正常对照组,B组右侧股骨头坏死组（20髋）,C组左侧带血管蒂大转子骨瓣修复组（20髋）。分别于术后3、6、10、12、18、24周行CT扫描,24周后行生物力学测试和股骨头三维有限元分析。结果24周后影像学检查发现C组大转子骨瓣与周围骨组织有很好的相融性,C组再造的股骨头抗压强度与A组正常接近,而与坏死股骨头统计学有明显的差异（P〈0．05）,三维有限元分析修复的股骨头最大应变和应力接近正常,而与坏死有显著的差别。结论带血管蒂大转子骨瓣修复股骨头能恢复其生物力学     

Localized osteoarticular change due to joint immobilization; biomechanical test and bone densitometry in rat's hind limb model

Bone change induced by knee immobilization was assessed on dissected femurs and tibias to clarify the influences upon the mechanical properties and their demands. Fifty-eight Wistar-Imamichi male rats (11–12 weeks old, body weight 350–450 g) were subjected to knee joint immobilization (150° flexed position) on one side while the opposite side served as a control. Animals were killed in seven groups at time intervals of 1, 2, 3, 4, 5, 7, and 10 weeks. The hind leg was extirpated and prepared for (1) biomechanical analysis by the indentation method at the articular surfaces of the femoral condyle and head and at the subchondral bone of the proximal tibia, and for (2) dual-energy X-ray absorptiometry of the distal metaphysis of the femur. The biomechanical parameters measured induced dynamic stiffness and phase lag derived from forced oscillation (preload 3 N, cyclic load 2 N and 11 Hz, 35 Hz), and bone mineral density was analyzed. These were compared between the immobilized side and control side, and among the seven time groups. The biomechanical results showed an early change of osteocartilaginous properties at the femoral condyle, a late response at the tibial subchondral bone, and no change at the femoral head. The measurement of bone mineral density revealed that a very sensitive reaction started within 1–2 weeks. This study provides objective data demonstrating that disuse or lack of mechanical stress greatly affects the remodeling activity for homeostasis of joints, and dramatically impairs normal bone mineral density next to the immobilized joint in young animals.     

Articular Cartilage Degradation and Aberrant Subchondral Bone Remodeling in Patients with Osteoarthritis and Osteoporosis

Osteoarthritis (OA) and osteoporosis (OP) are two skeletal disorders associated with joint structures. Occasionally, OA and OP occur in the same patient. However, the effect of OP changes on OA progression in patients with osteoporotic OA (OP-OA) has not been reported, especially the potential association between subchondral bone and articular cartilage. Thus we investigated the alterations in the microstructure, biomechanical properties, and remodeling of subchondral bone as well as their association with cartilage damage in the hip joint of patients with OP-OA. Thirty-nine femoral head specimens were obtained from patients who underwent total hip arthroplasty (OA group, n = 19; OP-OA group, n = 20), and healthy specimens from cadaver donors were used (control group, n = 10). The microstructure and biomechanical properties of subchondral bone were evaluated by micro–computed tomography and micro–finite-element analysis. Histology, histomorphometric measurements, and immunohistochemistry were used to assess subchondral bone remodeling and cartilage damage. Linear regression analysis was performed to elucidate the relationship between subchondral bone and articular cartilage. In the subchondral bone of the OP-OA group, compared with that of the OA group, aberrant bone remodeling leads to an inferior microstructure and worsening biomechanical properties, potentially affecting transmission of loading stress from the cartilage to the subchondral bone, and then resulting in accelerated OA progression in patients with OP-OA. The results indicate that changes in subchondral bone could affect OA development and the improvement in subchondral bone with bone-metabolism agents may help mitigate OA progression when OP and OA coexist in the same patients. © 2019 American Society for Bone and Mineral Research.     

双相磷酸钙组织工程骨块重建股骨头内骨缺损的实验研究

目的 观察在体外构建的具有仿生结构的双相磷酸钙（biphasic calcium phosphate，BCP）组织工程骨块植入犬股骨头缺损内的骨再生情况及预防股骨头塌陷的效果。方法 以犬股骨头的松质骨样本Micro—CT（micro—computed tomography）图像为基础，提取其中的图像信息，利用三维凝胶叠层成形法制备出具有仿骨小梁结构的陶瓷支架。在体外利用诱导分化的自体骨髓间充质细胞与仿生BCP支架复合，构建组织工程骨块，将其植入10只犬的股骨头负重区骨缺损内；另取10只火作为对照组，在股骨头骨缺损区内打球植入自体松质骨粒，对比观察仿生BCP骨块的植入效果。结果 制备出的股骨头仿生BCP支架具有良好的三维空间结构，支架小梁具有一定的方向性，呈板状模型；细胞在支架表面大量生长。植入动物体内30周后，实验组火股骨头外形基本完整，新生骨质包绕支架小梁并沿支架表面生长，而对照组犬股坩头均出现不同程度的塌陷。结论 仿生BCP组织工程骨块具有良好的生物相容性，植入犬股骨头负曩区骨缺损后，能在一定程度上防止股骨头塌陷。     

伞状支撑骨移植术治疗股骨头坏死的生物力学研究

目的 观察伞状支撑骨移植术治疗股骨头坏死的生物力学变化.方法 应用伞状支撑骨移植术(A组)治疗山羊股骨头坏死模型,并通过生物力学检测与单纯股方肌骨柱移植术组(B组)、骨髓间充质干细胞和松质骨移植术组(C组)进行对照研究(每组均14只).结果 术后3个月A组手术侧股骨头软骨下骨、松质骨的最大压强和弹性模量为:(77.43±2.65)、(120.60±4.18)MPa;(46.63±1.32)、(81.74±3.96)MPa.高于B组、C组(P＜0.05),与正常侧比较差异无统计学意义(P＞0.05).结论 伞状支撑骨移植术能有效恢复股骨头的生物力学强度,防止塌陷.     

Upregulation of VEGF in Subchondral Bone of Necrotic Femoral Heads in Rabbits with Use of Extracorporeal Shock Waves

Extracorporeal shock wave treatment appears to be effective in patients with avascular necrosis of the femoral head. However, the pathway of biological events whereby this is accomplished has not been fully elucidated. The purpose of this study was to investigate the effect of extracorporeal shock waves on vascular endothelial growth factor (VEGF) expression in necrotic femoral heads of rabbits. VEGF expression was assessed by immunohistochemistry, quantitative real-time PCR, and Western blot analysis. The degree of angiogenesis was also assessed, as determined by the microvessel density (MVD), the assessment of which was based on CD31-expressing vessels. Bilateral avascular necrosis of femoral heads was induced with methylprednisolone and lipopolysaccharide in 30 New Zealand rabbits. The left limb (the study side) received shock wave therapy to the femoral head. The right limb (the control side) received no shock wave therapy. Biopsies of the femoral heads were performed at 1, 2, 4, 8, and 12 weeks. Western blot analysis and real-time PCR showed that shock wave therapy significantly increased VEGF protein and mRNA expression, respectively, in the subchondral bone of the treated necrotic femoral heads. Compared with the contralateral control without shock wave treatment, the VEGF mRNA expression levels increased to a peak at 2 weeks after the shock wave treatment and remained high for 8 weeks, then declined at 12 weeks, whereas the VEGF protein expression levels increased to a peak at 4 weeks after the shock wave treatment and remained high for 12 weeks. The immunostaining of VEGF was weak in the control group, and the immunoreactivity level in the shock-wave-treated group increased at 4 weeks and persisted for 12 weeks. The most intensive VEGF immunoreactivity was observed in the proliferative zone above the necrotic zone. At 4, 8, and 12 weeks after the shock wave treatment, MVD in subchondral bone from treated femoral heads was significantly higher than that in subchondral bone from untreated femoral heads. These data clearly show that extracorporeal shock waves can significantly upregulate the expression of VEGF. The upregulation of VEGF may play a role in inducing the ingrowth of neovascularization and in improving the blood supply to the femoral head.     

bFGF/BMP/AACB复合物修复犬股骨头缺损坏死模型的实验研究

目的制备bFGF/BMP/AACB复合物,通过动物实验研究其对股骨头缺损坏死模型的修复作用及相关问题,探讨临床应用的可能性。方法制备异体脱抗原松质骨(AACB),并将其与碱性成纤维细胞生长因子(bFGF)及骨形态发生蛋白(BMP)复合制成bFGF/BMP/AACB复合物,植入通过液氮冷冻建立的犬股骨头缺损坏死模型,术后不同时间处死动物。通过大体解剖、X线片、组织学染色、图像分析、血管免疫组化染色、X线能谱分析、生物力学测定等手段观察缺损坏死模型的修复情况。结果术后各组动物均无毒性反应和炎症反应。A组(空白缺损组)术后12周缺损仍未愈合;B组(AACB组)虽然优于A组,但成骨作用不及C组(BMP/AACB组);而D组(bFGF/BMP/AACB组)成骨和成血管作用优于A、B、C组。早期(3、6周)甚至优于E组(自体骨组),后期(12周)的骨修复及骨改建效果与E组相当。结论bFGF/BMP/AACB复合物具有明显促进犬股骨头缺损坏死模型再血管化及新骨形成的作用,可望成为新型的股骨头缺血性坏死(ANFH)修复材料。     

Treatment of osteonecrosis of femoral head with BMSCs-seeded bio-derived bone materials combined with rhBMP-2 in rabbits

Objective： To evaluate the effect of autologous bone marrow mesenchymal stem cells （BMSCs） seeded bio-derived bone materials （BBM） combined with recombinant human bone morphogenetic protein-2 （rhBMP-2） in repairing defect of osteonecrosis of femoral head （ONFH）.
Methods： Early-stage osteonecrosis in the left hip was induced in 36 adult New Zealand white rabbits （provided by the Animal Center of Guangxi Medical University, Nanning, China） after core decompression and delivery of liquid nitrogen into the femoral head. Then the animals were divided into three groups according to the type of implants for bone repair： 12 rabbits with nothing （Group Ⅰ, the blank control group）, 12 with BBM combined with rhBMP-2 （Group Ⅱ）, and 12 with BMSCs-seeded BBM combined with rhBMP-2 （Group Ⅲ）. At 4, 8, and 12 weeks after surgery, X-ray of the femoral head of every 4 rabbits in each group was taken, and then they were killed and the femoral heads were collected at each time point, respectively. Gross observation was made on the femoral heads. After hematoxylin and eosin staining, Lane-sandhu scores of X-ray and bone densitometry were calculated and the histomorphometric measurements were made for the new bone trabeculae.
Results： At 12 weeks after surgery, two femoral heads collapsed in Group Ⅰ, but none in Group Ⅱ or Group Ⅲ. X-ray examination showed that the femoral heads in Group I had defect shadow or collapsed while those in Group II had a low density and those in Group III presented with a normal density. Histologically, the defects of femoral heads were primarily filled with no new bone but fibrous tissues in Group Ⅰ. In contrast, new bone regeneration and fibrous tissues occurred in Group II and only new bone regeneration occurrd in Group Ⅲ. Lane-sandhu scores of X-ray, bone mineral density and rate of new bone in trabecular area in Group Ⅲ were higher significantly than those of the other two groups. Conclusions： Our findings indicate a superior choice of     

激素性骨坏死关节软骨下皮质骨病理改变的实验研究

[目的]观察激素性骨坏死关节塌陷早期软骨下皮质骨的病理形态改变,分析关节塌陷的原因.[方法]将新西兰白兔分为两组,A组复制激素增强的Shwanzman反应骨坏死模型,B组为空白对照组.停药后10周获取肱骨头标本,分别制备脱钙和不脱钙切片,脱钙标本HE染色,观察软骨下皮质骨改变,哈佛管计数.不脱钙标本进行荧光观察,比较软骨下皮质骨形态、结构;扫描电镜观察,比较软骨下微循环改变、软骨下方骨组织形态、结构改变.[结果]A组标本出现坏死改变.软骨下方骨组织内哈佛管减少消失,即软骨下皮质骨及由其构成的球拱、桥拱结构破坏,支撑软骨层的骨组织呈松质骨改变.有部分肱骨头出现关节塌陷早期改变.软骨下微血管内广泛存在红细胞淤滞、填塞现象.B组软骨下方骨组织具有较丰富的哈佛管,为皮质骨.完整且连续的皮质骨支撑关节软骨,同时构成球拱、桥拱结构.软骨下微血管内无红细胞淤滞、填塞现象.[结论]关节软骨下皮质骨缺失是关节发生塌陷的原因.软骨下微循环障碍是其重要原因.