Effect of bone mesenchymal stem cells transplantation on the micro-environment of early osteonecrosis of the femoral head

Autologous implantation of bone mesenchymal stem cells (BMSCs) has achieved promising clinical efficacy for the treatment of early-stage osteonecrosis of the femoral head (ONFH). However, the underlying mechanisms are not completely elucidated. Here, we investigated the effect of BMSCs on the early ONFH in vitro and in vivo. In co-cultured system, primary BMSCs enhanced the activity and inhibited the apoptosis of primary OB. The concentrations of VEGF and BMP-2 in the co-cultured medium were significantly higher than those without co-culture. Importantly, BMSCs implantation increased OB, capillaries and VEGF and BMP-2 expressions of the necrotic areas of femoral head in the ONFH rabbits. In conclusion, our results indicated that BMSCs treated the early ONFH possibly through increasing OB and capillaries, as well as VEGF and BMP-2 expression in the femoral head. These results provided possible mechanisms for the treatment of early-stage ONFH with BMSCs transplantation.     

Micro-CT-based bone ceramic scaffolding and its performance after seeding with mesenchymal stem cells for repair of load-bearing bone defect in canine femoral head

Osteonecrosis of the femoral head is a debilitating and painful orthopedic condition characterized by joint collapse. Salvage of the femoral head is highly desirable to preserve the contour and mechanical properties and prevent joint collapse. This study aimed to develop a new tissue-engineering approach for treatment of large bone defect in femoral head, that is, after osteonecrosis. The biphasic calcium phosphate (BCP) ceramic scaffolds were fabricated by a 3D gel-lamination technique based on micro-computed tomography (micro-CT) images of the cancellous bone microarchitecture of femoral heads. After seeding with autologous bone marrow-derived mesenchymal stem cells (BMSCs) in vitro, the cell-scaffold composite was implanted into a bone defect surgically induced in canine femoral head via trapdoor procedure, which was a common procedure for treatment of osteonecrosis. A total of 24 adult dogs were randomly divided into three groups (n = 8 each) for implantation of the BCP scaffold with or without with BMSCs, and also the autologous bone chips for comparisons. All animals were sacrificed at 30 weeks postoperatively and processed for radiological and histological evaluations. The contour of the femoral head was well preserved with implantation of BCP scaffolds with or without BMSCs, whereas joint collapse was found after treatment with autologous bone chips. The osteointegration and new bone formation was significantly greater with BCP scaffold implantation with than without BMSC seeding and showed greater strength and compressive modulus in the repair site. Micro-CT-based bone ceramic scaffolds seeding with BMSC might be a promising way to repair bone defects in the femoral head.     

血管内皮生长因子与纳米晶胶原基骨支架复合修复大鼠股骨缺损

背景：研究证实纳米晶胶原基骨复合间充质干细胞修复骨缺损具有体内成骨能力。 目的：观察血管内皮生长因子与骨髓间充质干细胞、纳米晶胶原基骨复合物修复大鼠股骨缺损的效果。 方法：制作SD大鼠股骨中段骨缺损模型,随机分为2组：对照组植入骨髓间充质干细胞/纳米晶胶原基骨复合物;实验组植入血管内皮生长因子/骨髓间充质干细胞/纳米晶胶原基骨复合物。术后第2,4,8周行股骨标本影像学与组织学观察;术后第8周行新生骨痂环境扫描电镜检查。 结果与结论：纳米晶胶原基骨支架复合物植入大鼠体内后无排斥反应及炎症反应,且血管内皮生长因子/骨髓间充质干细胞/纳米晶胶原基骨复合物成骨更快,较骨髓间充质干细胞/纳米晶胶原基骨复合物具有更好的骨再生能力,其成骨方式主要为软骨内成骨。推测血管内皮生长因子促进了局部微血管的形成和成骨细胞的分化、增殖,加快了软骨内成骨的速率,缩短了骨修复时间,提高了骨再生的质量和速率。     

富血小板血浆联合骨髓间充质干细胞治疗家兔股骨头缺血坏死的研究

目的 评价比较富血小板血浆（PRP）联合骨髓间充质干细胞（BMSCs）移植修复家兔激素性股骨头缺血坏死与单纯BMSCs移植效果.方法 选取2只家兔自股骨骨髓离心提取BMSCs.选取40只家兔制作股骨头缺血坏死模型后,根据股骨头坏死临床诊断标准选取处于股骨头坏死Ⅰ、Ⅱ期阶段的30只家兔随机分为3组,每组10只.第一组10只患肢行钻孔减压后接受PRP联合BMSCs治疗（PRP联合BMSCs治疗组）;第二组10只患肢行钻孔减压后只接受单纯BMSCs治疗（单纯BMSCs治疗组）;第三组10只作为空白对照组,患肢行钻孔减压后接受注射用0.9％氯化钠溶液治疗.实验结果观察包括：治疗1周后利用聚合酶链反应检测各组转录生长因子（TGF-β）以及血管内皮生长因子（VEGF）含量;治疗5周后行切片分析以及BMSCs生长周期测定.结果 聚合酶链反应结果显示,PRP联合BMSCs治疗组分别与单纯BMSCs治疗组以及空白对照组比较,TGF-β的表达量存在差异,并具有统计学意义（3组间TGF-β含量分别为：1.5±0.46、1.2±0.36、0.4±0.12,P＜0.01）,VEGF的表达量存在差异,并具有统计学意义（3组间VEGF含量分别为：1.5 ±0.72、1.1±0.43、0.8±0.21,P＜0.01）;细胞周期测定显示PRP联合BMSCs治疗组与单纯BMSCs治疗组以及空白对照组相比,处于G1期数目较少,具有统计学意义（3组经治疗后处于G1期BMSCs的比例分别为：40％、60％、70％,P＜0.05）.结论 实验证明,PRP可以促进TGF-β以及VEGF的分泌,并且可以通过促进TGF-β以及VEGF的分泌对BMSCs的增殖有促进作用.与单纯BMSCs治疗相比,PRP联合BMSCs治疗股骨头缺血坏死可能是一种更有效的治疗方法.     

Evaluation of autologous bone marrow mesenchymal stem cell-calcium phosphate ceramic composite for lumbar fusion in rhesus monkey interbody fusion model

Autologous bone marrow mesenchymal stem cell (BMSC)-calcium phosphate ceramic composites were constructed in vitro and implanted as a bone graft substitute for lumbar anterior interbody fusion in rhesus monkeys to determine the osteogenic capacity of the composites. Nine adult rhesus monkeys underwent lumbar L3-L4 and L5-L6 diskectomy and interbody fusion via an anterior retroperitoneal approach. Two fusion sites in each animal were randomly assigned to two of three treatments: autogenous tricortical iliac crest bone graft (autograft group), cell-free ceramic graft (ceramic group), or BMSC-ceramic composite graft (BMSC group). Autologous BMSCs were expanded in culture and stimulated with osteogenic supplement. The spinal fusion segments were evaluated by radiography, biomechanical testing, histologic analysis, and histomorphometric analysis 3 months postsurgery. The BMSC group achieved lumbar interbody fusion superior to that of the ceramic group, both biomechanically and histologically. The BMSC group and the autograft group showed equivalent biomechanical stiffness. Ceramic residues were significantly greater in the ceramic group versus the BMSC group. The results indicate that BMSC-ceramic composites can enhance bone regeneration and achieve osseous spinal fusion 3 months after implantation in the rhesus monkey interbody fusion model.     

人血管内皮生长因子165基因转染兔骨髓间充质干细胞的蛋白表达

背景：骨髓间充质干细胞是最好的组织工程种子细胞来源,含有血管内皮生长因子165(vascular endothelial growth factor 165,VEGF165)不仅对血管再生和启动成骨修复有重要意义,其持续稳定的释放还能够提高新生骨的矿化程度,增强修复组织的力学性能。 目的：观察hVEGF165基因转染的兔骨髓间充质干细胞分泌血管内皮生长因子的蛋白功能。 方法：体外分离、培养兔骨髓间充质干细胞,纯化并鉴定兔骨髓间充质干细胞;免疫荧光法检测细胞表面标志;传代培养后的骨髓间充质干细胞以pcDNA3.1-VEGF165质粒和脂质体1∶3比例的混合液转染,并分为3组：转染组应用pcDNA3.1-VEGF165转染细胞,空载体转染组应用pcDNA3.1-空载体转染,未转染组不处理。通过ELISA和Western-blot检测转染后细胞中外源性血管内皮生长因子的表达。 结果与结论：转染组与其他两组比较,VEGF165蛋白含量显著增高,差异有显著性意义(P < 0.05),但空载体转染组与未转染组之间差异无显著性意义(P > 0.05),转染组不同时间点之间VEGF165蛋白含量差异均有显著性意义(P< 0.05),hVEGF165基因转染的骨髓间充质干细胞能成功分泌VEGF165蛋白。提示采用基因转染技术可将hVEGF165基因转染到骨髓间充质干细胞中并可有效表达具有生物活性的VEGF165。     

A Canine Model of Femoral Head Osteonecrosis Induced by an Ethanol Injection Navigated by a Novel Template

There is no consensus on how to establish models of osteonecrosis of the femoral head (ONFH) in large mammals. The aim of this study was to investigate the effectiveness of a novel canine model of ONFH, induced by a navigated injection of absolute ethanol. Using three-dimensional reconstruction and rapid prototyping manufacturing techniques, a new template was designed and processed to navigate the ethanol injection. The femoral heads of 18 adult dogs were injected with ethanol. Macroscopic, X-ray and histological examinations were performed at 3, 6, and 9 weeks after the operation. Further, computed tomography (CT), magnetic resonance imaging (MRI), and radionuclide scans were performed 6 weeks postoperatively. Three weeks after the operation, the femoral heads showed evidence of osteonecrosis including increasing numbers of empty lacunae, decreased hematopoietic cells, and destroyed adipose tissue in the medullary cavity, which increased in severity at the subsequent follow-up evaluations at 6 and 9 weeks. Fractured trabeculae and fibrous tissue were noted 9 weeks postoperatively. Image analysis also revealed evidence of osteonecrosis, such as several osteopenic areas with sclerotic rims on the X-ray, several areas of low bone mineral density with sclerosis on the CT scan, increased uptake of the nuclide species in MRI, and an inhomogeneous long T2 signal on the radioisotopic images. Ethanol injection navigated by our novel template was successful in establishing a canine model of ONFH. This model can be used to test new treatment modalities for human ONFH.     

Can bisphenol A diglycidyl ether (BADGE) administration prevent steroid-induced femoral head osteonecrosis in the early stage?

Steroid-induced osteonecrosis of the femoral head (ONFH) is associated with increase of intraosseous pressure caused by elevating of adipogenesis and fat cell hypertrophy in the bone marrow, which subsequently decreases the blood flow in the femoral head and finally resulting in bone ischemia. The early femoral head-preserving method has mainly focused on the conventional core decompression procedure. However, it only achieves a slight decrease in intra-medullary pressure with limited clinical outcome. The crucial point in prevention is to achieve a thorough decompression of intra-medullary pressure and improvement of microcirculation of the femoral head. Bisphenol-A-diglycidyl ether (BADGE), an antagonism of PPAR-γ(Peroxisome proliferator-activated receptor gamma), has been shown to successfully reverse bone marrow adipogenesis and fat cell hypertrophy, enhances proliferation of osteoblasts, inhibit osteoclastogenesis. Therefore, we hypothesized that BADGE administration may be an appropriate novel method for the prevention of early stage steroid-induced ONFH.     

三足负重犬股骨头坏死模型的生物力学相关性研究

目的研究股骨头坏死病程各阶段的生物力学改变,探讨其生物力学发生作用的机制。方法取杂种犬24只,固定一侧前肢建立三足负重犬模型。随机取三足负重犬一侧后肢为实验侧,在股骨头内注射无水酒精,致股骨头坏死;对侧为对照侧,在股骨头内注入等量生理盐水。造模后1、3、6及12周处死动物,每组6只,分别对两组股骨头行大体观察以及放射学、组织学、生物力学检测。结果术后3周股骨头坏死侧点压硬度及中部松质骨弹性模量相对对照侧分别下降29%和32.9%,此时仅MRI可见股骨头出现低密度坏死区,组织学主要表现为骨坏死。术后6、12周股骨头坏死侧点压硬度相对对照侧分别下降了45.5%和48.7%,中部松质骨弹性模量相对对照侧分别下降了34.1%和32.4%。6周时坏死侧X线可见股骨头内密度不均,组织学表现为坏死和修复反应并存,坏死区向软骨下骨区进展。12周时坏死侧X线可见股骨头负重区下出现局部骨密度减低区,组织学出现关节软骨面塌陷和关节间隙狭窄。结论生物力学是股骨头病程进展的重要影响因素;病程进展中,特别是修复期力学性能的显著下降可能是后期塌陷的最直接原因。治疗股骨头坏死不仅应促进骨修复,更应提供病变区一个有利、稳定的生物力学环境。     

Augmented healing of critical-size calvarial defects by baculovirus-engineered MSCs that persistently express growth factors

Repair of large calvarial bony defects remains clinically challenging because successful spontaneous calvarial re-ossification rarely occurs. Although bone marrow-derived mesenchymal stem cells (BMSCs) genetically engineered with baculovirus (BV) for transient expression of osteogenic/angiogenic factors hold promise for bone engineering, we hypothesized that calvarial bone healing necessitates prolonged growth factor expression. Therefore, we employed a hybrid BV vector system whereby one BV expressed FLP while the other harbored the BMP2 (or VEGF) cassette flanked by Frt sequences. Transduction of rabbit BMSCs with the FLP/Frt-based BV vector led to FLP-mediated episome formation, which not only extended the BMP2/VEGF expression beyond 28 days but augmented the BMSCs osteogenesis. After allotransplantation into rabbits, X-ray, PET/CT, μCT and histological analyses demonstrated that the sustained BMP2/VEGF expression remarkably ameliorated the angiogenesis and regeneration of critical-size (8 mm) calvarial defects, when compared with the group implanted with BMSCs transiently expressing BMP2/VEGF. The prolonged expression by BMSCs accelerated the bone remodeling and regenerated the bone through the natural intramembranous pathway, filling ≈83% of the area and ≈63% of the volume in 12 weeks. These data implicated the potential of the hybrid BV vector to engineer BMSCs for sustained BMP2/VEGF expression and the repair of critical-size calvarial defects.     

Systemic BMSC homing in the regeneration of pulp-like tissue and the enhancing effect of stromal cell-derived factor-1 on BMSC homing

Pulp regeneration caused by endogenous cells homing has become the new research spot in endodontics. However, the source of functional cells that are involved in and contributed to the reconstituting process has not been identified. In this study, the possible role of systemical BMSC in pulp regeneration and the effect of stromal cell-derived factor-1 (SDF-1) on stem cell recruitment and angiogenesis were evaluated. 54 mice were divided into three groups: SDF-1 group (subcutaneous pockets containing roots with SDF-1 absorbed neutralized collagen gel and the green fluorescent protein (GFP) positive BMSCs transplantation via the tail vein), SDF-1-free group (pockets containing roots with gel alone and GFP + BMSCs transplantation) and Control group (pockets containing roots with gel alone). The animals were sacrificed after the roots were implanted into subcutaneous pockets for 3 weeks. Histomorphometric analysis was performed to evaluate the regenerated tissue in the canal by hematoxylin and eosin (HE) staining. The homing of the transplanted BMSCs was monitored with a fluorescence microscope and immunohistochemical analysis. The expression of ALP in new formed tissue was detected immunohistochemically. Dental-pulp-like tissue and new vessels were regenerated and GFP-positive BMSCs and expression of ALP could be observed in both SDF-1 group and SDF-1-free group. Furthermore, more GFP+ cells, stronger expression of ALP and stronger angiogenesis were found in the SDF-1 group than in the SDF-1-free group. To conclude, systemic BMSC can home to the root canal and participate in dental-pulp-like tissue regeneration. Intracanal application of SDF-1 may enhance BMSC homing efficiency and angiogenesis.     

双基因转染犬骨髓间充质干细胞复合HA/ZrO2生物材料新型组织工程骨的构建及其体外成骨能力的研究

目的 构建骨形态发生蛋白2(BMP-2)、血管内皮细胞生长因子165(VEGF165)双基因修饰的骨髓间充质干细胞(BMSCs)复合羟基磷灰石复合二氧化锆(HA/ZrO₂)生物材料的新型组织工程骨,并观察该组织工程骨在体外的成骨能力。方法 采用有机泡沫作为模版,干铺烧制法制备新型的蜂窝状HA/ZrO₂梯度生物材料,电镜观察新型生物材料的表面特性,生物力学试验机检测其力学性能。采取1岁龄健康beagle犬骨髓分离原代BMSCs进行培养,建立双基因修饰的BMSCs复合蜂窝状HA/ZrO₂梯度生物材料的共培养体,构建新型组织工程骨。实验分为4组:未转染组,只转染BMP-2(BMP-2组)和VEGF165(VEGF165组)单一目的基因的BMSCs,以及转染BMP-2、VEGF165共基因慢病毒的BMSCs组(BMP-2+VEGF165组)。显微镜下观察细胞在支架材料上的生长情况,用碱性磷酸酶染色检测各组细胞成骨分化能力,免疫组织化学染色检测其成骨细胞特异性蛋白骨Ⅰ型胶原及骨钙素的分泌。结果 新型材料电镜下其表面整体呈多孔状,孔径125~550 μm,各孔之间存在缝隙联结;其平均抗弯强度为812.25 MPa,最高可达987.12 MPa;共培养体建立后扫描电镜观察转染后的BMSCs在支架材料上黏附生长状况良好,双基因联合转染组细胞分泌基质旺盛;BMP-2+VEGF165组细胞碱性磷酸酶活性检测明显高于其他各组(F=1 029.398,P<0.01),免疫组织化学染色在不同阶段发现成骨细胞早晚期分泌的骨Ⅰ型胶原及骨钙素特异性蛋白。结论 新型的蜂窝状HA/ZrO₂梯度生物材料是一种合适种子细胞生长的支架材料,并且其力学满足人体四肢承重骨的需要;VEGF165、BMP-2双基因转染BMSCs后具有协同作用,能够促进其在体外的成骨分化。     

The influence of osteoblast differentiation stage on bone formation in autogenously implanted cell-based poly(lactide-co-glycolide) and calcium phosphate constructs

We tested the hypothesis that the osteoblast differentiation status of bone marrow stem cells (BMSCs) combined with a three-dimensional (3D) structure modulates bone formation when autogenously implanted. Rat BMSCs were aspirated, expanded, and seeded into a 3D composite of poly(lactide-co-glycolide) and calcium phosphate (PLGA/CaP) to produce a hybrid biomaterial. Calvarial defects were implanted with (1) scaffold without cells (SC/NC), (2) scaffold and BMSCs (SC+BMSC), (3) scaffold and osteoblasts differentiated for 7 days (SC+OB7), and (4) for 14 days (SC+OB14). After 4 weeks, there was more bone formation in groups combining scaffold and cells, SC+BMSC and SC+OB7. A nonsignificant higher amount of bone formation was observed on SC+OB14 compared with SC/NC. Additionally, more blood vessels were counted within all hybrid biomaterials, without differences among them, than into SC/NC. These findings provide evidences that the cell differentiation status affects in vivo bone formation in autogenously implanted cell-based constructs. Undifferentiated BMSCs or osteoblasts in early stage of differentiation combined with PLGA/CaP scaffold favored bone formation compared with plain scaffold and that one associated with more mature osteoblasts.     

Can local Erythropoietin administration enhance bone regeneration in osteonecrosis of femoral head?

Osteonecrosis of femoral head (ONFH) is a challenging disease. Regardless of underlying causes, the ultimate result in all cases is disruption of femoral head blood supply. Once the disease starts, it is progressive in 80% of cases. Since the majority of the affected individuals are young, every effort should be focused on preserving the patients own femoral head. These years, the role of angiogenic growth factors has been investigated with promising results in animal models of ONFH. Erythropoietin (EPO) is a well known hormone that has been used in treatment of chronic anemia for many years with few side effects. Considering the angiogenic properties of EPO, we hypothesize that local delivery of recombinant human EPO during core decompression will enhance bone regeneration in ONFH. In this way we also can avoid systemic side effects of EPO.     

骨内注射无水乙醇建立兔股骨头坏死模型

背景：目前还难以建立合适的早期股骨头坏死的动物模型。 目的：建立一个简单、标准和可靠的股骨头坏死动物模型用于实验研究。 方法：X射线透视下将新西兰兔右侧股骨头中心钻孔并注入无水乙醇,左侧不做处理做对照。经过2,4和6周麻醉下处死动物获取股骨头。 结果与结论：大体及X射线观察显示,造模侧股骨头第2周关节软骨颜色变暗、骨质密度不均匀;第6周,关节面有轻微凹陷,骨质低密度影较前进一步增大。MRI显示,造模侧股骨头第2周,T1加权股骨头负重区显示线样或不规则低信号,T2加权呈高信号;第6周,股骨头变性,软骨下骨折,关节面塌陷,新月体形成。对照侧第2,4,6周股骨头结果均常。组织病理学观察显示,造模侧股骨头第2周后,骨细胞核固缩、变性坏死。结果证实,2周后兔股骨头均发生了部分坏死,股骨头坏死的完整的外观形态,大体循环和关节软骨与人类早期股骨头坏死是相似的,提示实验建立了良好的股骨头坏死动物模型。     

Osteogenic differentiation and angiogenesis with cocultured adipose-derived stromal cells and bone marrow stromal cells

The purpose of this study was to determine the influence of cocultured adipose-derived stromal cells (ASCs) in enhancing the osteogenic differentiation and angiogenesis of bone marrow stromal cells (BMSCs) as well as the underlying mechanism and the optimal ratio. Two in vitro coculture models, segregated cocultures using transwell and mixed cocultures, were employed to assess the indirect and direct effects of coculture respectively. Coculture was carried out for 14 days using 1 × 10⁵ BMSCs and ASCs of variable number. BMSCs, ASCs, or both were seeded in PLGA scaffold and implanted in the subcutaneous tissue of 25 nude mice for in vivo analysis of angiogenesis. To evaluate the orthotopic bone formation, critical size calvarial defects were created on 20 mice, and implanted with hydroxyapatite/β-tricalcium phosphate granules plus BMSCs, ASCs, or both. From both transwell and mixed coculture model, 1 × 10⁵ BMSCs cocultured with 0.5 × 10⁵ ASCs showed significantly greater osteogenic differentiation and mineralization than BMSCs alone. The mixed ASC/BMSC coculture at or above a ratio of 0.5/1 showed increased secretion of vascular endothelial growth factor (VEGF), and induced effective tube formation from human umbilical vein endothelial cells, which were comparable to ASCs. Cytokine profiling assay and gene expression study showed elevated levels of angiogenic factors VEGF and CXCL1, osteogenic factor Wnt5a as well as transforming growth factor (TGF)-βR1 and SMAD3 from BMSCs when cocultured with ASCs. After 5 weeks of implantation, polylactic-co-glycolic acid (PLGA)-ASCs-BMSCs had a number of vascular structures comparable to PLGA-ASCs and significantly greater than PLGA-BMSCs. Calvarial defects treated with ceramic/BMSCs/ASCs had greater area of repair and better reconstitution of osseous structure than the defects treated with ceramic/ASCs or ceramic/BMSCs after 10 weeks. In conclusion, ASCs added to BMSCs promoted osteogenesis and angiogenesis at the optimal ASC/BMSC ratio of 0.5/1.     

体外冲击波疗法结合同种异体骨钉治疗成人股骨头缺血性坏死

目的探讨体外冲击波疗法（ESWT）结合同种异体骨钉治疗成人股骨头缺血性坏死的疗效。方法2003年7月～2007年1月,采用体外冲击波或结合同种异体皮质骨钉植入术治疗54例（84髋）股骨头缺血性坏死患者并随访观察。男41例,女13例;年龄20～61岁,平均30岁。按Ficat分期,Ⅱ期55髋,Ⅲ期29髋。其中40髋（Ⅱ期27髋,Ⅲ期13髋）,采用ESWT结合同种异体骨钉治疗,治疗后6、12、24个月复查双髋X线、MRI及髋关节Harris评分（HHS）。44髋（Ⅱ期28髋,Ⅲ期16髋）患者采用单纯ESWT治疗。对两组治疗结果进行统计学分析。结果随访24～29个月,平均25．7个月。二者治疗后Harris评分分别为83．71±18．76和57．20±12．82,二者比较差异有统计学意义妒〈0．01）：影像学X光片评估：ESWT结合同种异体骨钉术后随访股骨头塌陷12髋,塌陷率为30％,单纯ESWT治疗随访股骨头塌陷25髋,塌陷率为56．8％。结论体外冲击波疗法结合同种异体骨钉是治疗中期ONFH的方法之一,它不但具有冲击波疗法促进骨愈合作用,而且复合骨钉移植可起到骨传导及骨支撑作用,近期可以减少股骨头塌陷发生。     

Treatment of osteonecrosis of the femoral head: combination of operation and multiple cellular mediators

The goal in the treatment of osteonecrosis of the femoral head is to preserve, not replace, the femoral head. Although many methods have been proposed, none has proved completely satisfactory. Cellular mediators as a supplement to bone grafting and decompression is an attractive approach to this problem because it combines the desirable features of other procedures, each of which has shown a certain degree of effectiveness in stimulating bone growth and repair. Basic and clinical researches have shown the efficacy of various cellular mediators (bone morphogenetic proteins, interleukins, angiogenic growth factors, etc.) in healing bone defects. The potential application of these cellular mediators to other musculoskeletal conditions, including osteonecrosis of the femoral head, only recently has been explored. The surgical alternatives may include core decompression, osteotomy, nonvascularized, and vascularized bone grafting, which might be enhanced with the use of cellular mediators. At least three of these factors are potential candidates as therapeutic modalities: cytokines, bone morphogenetic proteins, and angiogenic factors. Therefore, we hypothesized that the combination of operation and multiple cellular mediators is an attractive method to preserve the femoral head for the therapy of osteonecrosis of the femoral head.     

转染血管内皮细胞生长因子骨髓间充质干细胞与牛松质骨支架复合组织工程骨的血管形成

背景：小块组织工程骨植入动物体内后,早期依靠组织液的渗透可获得营养,但大块组织工程骨的营养仅靠组织液的渗透是远远不够的,必须通过血管再生来获得。 目的：观察转染血管内皮细胞生长因子表达载体骨髓间充质干细胞复合组织工程骨植入动物体内后的血管形成能力。 方法：制作日本大耳白兔双侧尺骨中段骨缺损模型,左侧尺骨缺损植入转染血管内皮细胞生长因子表达载体的自体骨髓间充质干细胞复合脱钙脱脂去蛋白的牛松质骨支架组织工程骨为实验组,右侧尺骨缺损植入自体骨髓间充质干细胞复合脱钙脱脂去蛋白的牛松质骨支架组织工程骨为对照组。术后12周行X射线摄片观察、大体标本观察、苏木精-伊红染色和Masson染色组织切片观察、MiFas图像分析系统定量分析。 结果与结论：实验组与对照组尺骨缺损处均有连续骨痂形成;组织切片经苏木精-伊红染色、Masson三色法染色及MiFas图像分析系统定量分析可见实验组和对照组均有大量的新生骨,但实验组新生血管明显多于对照组(P < 0.01),且血管较粗大,而且与新生骨接近。说明将转染血管内皮细胞生长因子表达载体的骨髓间充质干细胞复合在组织工程骨上植入动物体内可明显促进新生血管的形成。     

计算机软件测定股骨头坏死的体积及其意义

目的评估计算机软件测定股骨头坏死体积比的准确性。方法 20个比格犬(40髋)通过液氮冷冻法制成双侧股骨头坏死模型,对股骨头坏死区域体积比通过二种不同的方法来计算:①通过液体测量法测定股骨头体积和坏死股骨头体积,二者相除即为体积比;②将坏死模型的MRI图像以Dicom导入Minics,重建坏死区与股骨头的三维图像,通过逆向工程软件Geomagic处理后,导入Ansys软件划分单元,计算所有坏死单元的体积与整个股骨头单元体积比。结果计算机软件计算的体积比结果为(26.4±10.2)%,实体测定的体积比为(25.8±10.6)%,通过SPPS11.0分析,无统计学差异。结论计算机软件能准确评估股骨头坏死区域体积比,是一个可以提倡的新方法。