量化比较带蒂筋膜瓣促血管化成骨与膜诱导成骨作用及成骨效果的实验研究

目的通过量化指标测定,明确带蒂筋膜瓣包裹自体骨髓基质干细胞（BMSC）接种的非细胞型组织工程骨在修复骨缺损各时间段中的主要作用及成骨效果,为临床干预骨缺损的治疗提供依据。方法制作动物骨缺损模型及带蒂筋膜瓣,随机分为A、B、C三组,A组为单纯植入对照组,B组为无蒂筋膜瓣对照组,C组为带蒂筋膜瓣实验组,在第4、8、12、16周进行骨修复区吸光度比测量、骨形态计量分析、交界区和中心区血管图像计量分析,第8、12、16周同时进行放射性核素骨显像检查、腋动脉注入墨汁检查及生物力学测定分析。结果第4、8周时,C组与A组、B组相比较其骨修复区吸光度比值、新生骨小梁面积、再生血管面积和放射性核素骨显像摄取比值明显增多,生物力学强度增加,各项量化指标差异均有统计学意义（P〈0.05）,表现为早期骨修复过程中血管体积增多对成骨作用是有利的;第12、16周时,三组骨修复区吸光度比测量、新生骨小梁面积和生物力学强度逐渐明显增加,C组仍大于A组、B组,但各组再生血管面积和放射性核素骨显像摄取比值较第8周下降明显,差异有统计学意义（P〈0.05）,表现为随着时间的推移,成熟骨组织量的增多,血管化作用逐渐减弱,后期膜诱导成骨作用显著。结论带蒂筋膜瓣包裹自体BMSC接种的非细胞型组织工程骨具有构建血管化和膜诱导组织再生双重作用,早期促血管化成骨作用占主导地位,并有助于膜诱导成骨作用,后期膜诱导成骨作用为主,促血管化成骨作用消失,临床适时干预治疗对骨缺损修复有极好作用。     

带蒂筋膜瓣促非细胞型组织工程化骨血管化及其成骨的组织学变化****

背景：目前关于带蒂筋膜瓣促组织工程骨成骨是否以早期促血管化为核心的成骨修复方式的对比研究还缺少相关报道。 目的：通过带蒂筋膜瓣在修复骨缺损各时间段中促非细胞型组织工程化骨血管化及其对成骨作用影响组织学观察,论证带蒂筋膜瓣具有较好的促血管化作用及促成骨能力。 方法：制作兔尺骨长段骨-骨膜完全缺损模型及带蒂筋膜瓣,随机分为单纯植入组、无蒂膜瓣包裹组、血管内皮生长因子组、膜瓣包裹组4组,分别于骨缺损处植入相应材料。 结果与结论：组织学显示,在各时间点无论新生血管数量,还是新生骨小梁质与量,膜瓣包裹组均明显优其他3组。血管再生面积和新生骨小梁面积测定显示,第4周血管内皮生长因子组、膜瓣包裹组明显多于单纯植入组、无蒂膜瓣包裹组        (P < 0.05);植入后第8,12,16周膜瓣包裹组骨修复区血管再生面积及对应的再生骨小梁面积明显多于其他3组(P < 0.05)。提示带蒂筋膜瓣具有显著促非细胞型组织工程化骨血管化作用,血管化增强有利于成骨作用,且可有效提高成骨质和量、缩短骨修复时间。      

以带蒂筋膜瓣为膜材料应用GBR技术修复兔骨缺损的血管化作用及成骨方式研究

目的研究带蒂筋膜瓣作为膜材料应用于膜引导性骨再生技术修复骨缺损的过程中血管化进程及成骨效果方法24只5月龄新西兰大白兔雌雄不限,制备双侧尺骨1cm骨缺损模型,自体红骨髓（au-tologous red bone marrow,ARBM）接种于骨诱导活性材料（Osteoinductive absorbing material,OAM）制备组织工程骨。将非细胞型组织工程复合物植入骨缺损区,右侧单纯可吸收生物膜包裹设为A组,左侧带血运深筋膜瓣包裹设为B组。各组在4、8、12、16周后进行X线检查、光密度比值测量、大体观察和组织学检查、交界区血管图像计量分析,将数据作统计学处理,用以比较骨缺损修复情况。结果X线片、大体形态和组织学观察显示,植入物内部血管的长入、骨小梁及软骨组织形成的数量和速度、成熟骨结构的形成、骨干结构的重塑、骨髓腔的再通、植入物的吸收降解,筋膜瓣组均明显优于生物膜组。光密度比值测量显示,术后8、12、16周两组间比较及同组内各时间点间比较差异均有统计学意义（P〈0.05）,术后4、8、12、16周,骨修复交界区单位面积内血管再生面积筋膜瓣组明显多于生物膜组,差异有统计学意义（P〈0.05）。从术后12周,筋膜瓣组随着成熟骨结构形成,血管结构减少或消失。结论带血运筋膜瓣具有明显的促组织工程骨血管化作用并通过促血管化而促进成骨并具备膜引导性骨再生（guided bone regeneration,GBR）技术的骨修复特点,即早期促进外骨痂生长。     

放射性核素骨显像在骨缺损修复实验中的研究

目的：通过动物实验探讨多孔纳米羟基磷灰石人工骨（nano-HA）的骨缺损修复作用及放射性核素骨显像在骨重建过程中的应用，为临床运用于骨缺损修复领域提供依据。方法：采用新西兰大白兔24只在单侧桡骨制备骨缺损动物模型，然后用多孔纳米羟基磷灰石人工骨材料进行植入骨缺损处进行修复作为实验组，以普通羟基磷灰石人工骨材料作为对照组；术后2周，4周，8周和12周分别行放射性核素骨显像监测两组人工骨对骨缺损的修复能力。结果：通过ROI方法定量对比两种材料植入区和正常区放射性浓集比值，nano-HA人工骨组成骨作用优于HA人工骨组，骨缺损修复能力优于后者，差异有统计学意义（P〈0．05）。结论：纳米羟基磷灰石人工骨具有良好的成骨能力，可望成为新型的骨缺损修复材料，放射性核素骨显像在骨修复过程中具有良好的监测作用。     

生物膜与带蒂筋膜瓣体内构建组织工程复合体修复兔骨缺损的比较

背景：利用带蒂筋膜瓣包裹法及单纯生物膜包裹构建组织工程骨均能有效促进骨修复,目前缺乏此两方面的对比研究。 目的：观察单纯生物膜包裹及带蒂筋膜瓣包裹法构建组织工程骨修复骨缺损的效果。 方法：制备兔双侧尺骨中段连同骨膜1 cm骨缺损模型,将自体红骨髓接种于含骨形态发生蛋白的骨诱导活性材料制备非细胞型组织工程骨,并植入双侧骨缺损区,左侧采用深筋膜瓣包裹,设为实验组,右侧采用单纯可吸收生物膜包裹,设为对照组。4,8,12,16周后进行X射线检查、大体观察和组织学检查、修复区内骨形态计量分析,并在12周行生物力学检测,比较两组骨缺损修复情况。 结果与结论：实验组X射线片、大体形态和组织学观察、骨小梁及软骨组织形成的数量和速度、成熟骨结构的形成、骨干结构的重塑、骨髓腔的再通、植入物的吸收降解、新生骨小梁面积占修复总面积比值以及最终生物力学强度均明显优于对照组(P < 0.05)。说明以带蒂筋膜瓣为膜材料应用膜引导性骨再生技术修复大段骨缺损,能有效限制纤维结缔组织长入,具有有效快速血管化能力,极大地加快了移植骨转化为自体骨的速度及效果。     

核素骨显像评价组织工程骨修复骨缺损效果的价值

目的 应用放射性核素骨显像评价组织工程骨修复兔股骨髁骨缺损的效果。方法 取人白兔15只，抽取骨髓，行骨髓间充质干细胞分离、培养、骨向诱导。双侧股骨髁制作0．6×1．2cm的骨缺损，将诱导的成骨细胞复合珊瑚羟基磷灰石植入左侧，右侧单纯植入羟基磷灰石为对照组。术后4间、8周和12周分别行静态核素骨显像评价骨缺损的修复能力。结果表明术后4、8、12周实验组ROI计数（单位像素）均较对照组有显著性增高（P〈0．001）。实验组ROI计数随时间的延长呈明显的上升趋势，但术后8周始增长放缓；对照组ROI也有卜升趋势，但术后8周始增长加快，均在12周达到峰值。结论 骨髓间充质干细胞诱导后复合珊瑚羟基磷灰石可有效的修复股骨髁松质骨缺损。放射性核素骨显像在骨修复过程中具有动态评价血管化和骨生长的作用。     

纳米羟基磷灰石人工骨修复骨缺损的再血管化研究

目的通过动物实验探讨多孔纳米羟基磷灰石人工骨（Nano-HA）的骨缺损修复作用并观察骨重建过程中再血管化过程。方法采用新西兰大白兔24只在单侧桡骨制备骨缺损动物模型，然后用纳米羟基磷灰石人工骨材料进行植入骨缺损处进行修复作为实验组，以普通羟基磷灰石人工骨材料作为对照组；术后2，4，8和12周分别行钟^99mTc-亚甲基二膦酸盐（MDP）放射性核素骨显像监测在骨缺损修复中再血管化的过程，并以x线、组织学检查作比较。结果通过ROI方法定量对比两种材料植入区和正常区放射性浓集比值，Nano-HA人工骨组成骨代谢明显优于HA人工骨组，骨缺损修复能力明显优于后者，差异有统计学意义（P〈0．05）。结论纳米羟基磷灰石人工骨具有优异的成骨能力，可望成为新型的骨缺损修复材料，放射性核素骨显像是监测骨修复再血管化过程敏感、直观、可靠的方法。     

聚羟基丁酸-羟基戊酸共聚酯膜与聚羟基丁酸-羟基戊酸共聚酯-溶胶-凝胶生物活性玻璃复合材料修复骨缺损的研究

目的 探讨聚羟基丁酸-羟基戊酸共聚酯(PHBV)膜与PHBV-溶胶-凝胶生物活性玻璃(PHBV-SGBG)多孔复合材料促进骨再生的能力.方法 制备犬胫骨骨缺损模型,实验分4组:PHBV膜+PHBV-SGBG组;PHBV膜组;PHBV-SGBG组;空白对照组.术后2、4、8、12周取材,扫描电镜下观察各组骨缺损区的骨生长情况,并进行新骨的Ca、P元素微区定量测定.结果 所有植入材料组(PHBV膜+PHBV-SGBG组、PHBV膜组、PHBV-SGBG组)均可不同程度地促进新骨的形成.术后12周,PHBV膜+PHBV-SGBG组骨缺损区的修复重建基本完成,新生骨的Ca/P比值(1.625±0.037)与周围正常骨的Ca/P比值(1.625±0.063)差异无统计学意义(P＞0.05);空白对照组的新生骨质疏松有洞,显示有较高的有机组织能谱;PHBV-SGBG组的骨修复略优于PHBV膜组,但两组间的差异无统计学意义(P＞0.05).结论 PHBV膜具有引导骨再生的能力,PHBV-SGBG复合材料具有很好的骨传导性和骨形成能力,联合应用PHBV膜和PHBV-SGBG复合材料具有促进骨缺损修复的协同作用.     

带血供的骨膜瓣修复兔关节软骨缺损的实验研究

目的:设计带血供的骨膜瓣转位修复兔关节软骨缺损,以探索小动脉血管蒂骨膜瓣修复关节软骨的可能性。方法:骨刀在髌股关节的股骨侧软骨面制造6mm×8mm软骨缺损,以兔隐动脉关节支为蒂,切取股骨内髁骨膜瓣7mm×9mm,右侧骨膜瓣生发层朝向关节腔覆盖软骨缺损区(实验组),左侧骨膜瓣生发层朝向骨面覆盖软骨缺损区(对照组)。术后2、4、8、12、16周后处死取材,分别作肉眼、光学显微镜及电子显微镜观察。结果:所有骨膜瓣均存活,肉眼观察见两侧新生组织类似关节软骨,光镜和电镜观察见右侧软骨修复优于左侧。结论:带小动脉血管蒂骨膜瓣转位可修复关节软骨缺损,再生软骨接近透明软骨。     

四肢带血管蒂骨（膜）瓣移位术新供区的解剖学基础

目的:介绍上、下肢带血管蒂骨瓣、骨膜瓣移位术新供区的解剖学依据,指导术式设计和推广应用。方法:综合作者近年新发掘的四肢骨瓣、骨膜瓣新供区的解剖学资料,针对性地设计了常用的移位术式。结果:这一批供区以非主干知名血管或主干血管的小分支为血管蒂,设计的骨瓣、骨膜骨瓣.顺行或逆行移位修复四肢骨不连、骨缺损、骨缺血性坏死,临床应用获得了可靠的治疗效果。结论:四肢带血供的骨(膜)瓣移位术供区,术式设计合理,手术操作简便,对供区功能影响很小,适合在基层医疗单位推广。     

Strategies of enhancing bone regenerate formation in distraction osteogenesis

Distraction osteogenesis (DO) is a commonly used technique in multiple orthopedic sub-specialties, including trauma, oncology and pediatrics. This technique aims to produce new bone formation in the distraction gap in a controlled manner. The issue with this technique has been the high risk of complications, one of which is poor regenerate formation during the distraction process. Although several factors (including patient and operative factors) and techniques (including surgical, mechanical and pharmacological) have been described to ensure successful regenerate formation during the process of DO, these factors are sometimes difficult to control clinically. Our aim from this review is to highlight the different factors that affect DO, modalities to assess the regenerate and review treatment options for poor regenerate in the distraction gap. In addition, we propose a management protocol derived from the available literature that can be used to facilitate the management of inadequate regenerate formation.     

Distraction osteogenesis as a salvage method in infected knee megaprostheses

Infection of total knee replacement represents a severe complication. Especially in cases of infected megaprostheses, treatment options are limited and even amputation may become unavoidable. We present two cases of infected knee hinged megaprostheses. Both were treated by prosthesis removal and debridement of all surrounding infected bone and soft tissue, followed by distraction osteogenesis for the bridging of the large bone defect which had resulted. Implant removal and surgical debridement were combined with Ilizarov frame application and femoral and tibial osteotomies in a one-stage procedure, for commencing distraction osteogenesis. After bone transportation was completed, arthrodesis of the knee in both cases was successful. Two years after completion of the treatment, both patients demonstrate a stable knee arthrodesis and a satisfactory clinical result. The described treatment plan represents an effective salvage method in cases of infected knee megaprostheses that can successfully address both the need for a stable arthrodesis and the avoidance of a severe leg-length discrepancy by bridging the extensive bone defect.     

microRNA-146a mediates distraction osteogenesis via bone mesenchymal stem cell inflammatory response

Distraction osteogenesis (DO) is a widely used surgical technique to repair bone defects, partly owing to its high efficiency in inducing osteogenesis; however, the process of osteogenesis is complex, and the precise mechanism is still unclear. Among the factors identified for an effective DO procedure, well-controlled inflammation is essential. We aimed to explore how microRNA(miR)?146a, a negative regulator of inflammation, influences osteogenesis in DO. First, we established canine right mandibular DO and bone fracture models to evaluate the expression level of miR-146a in response to these procedures. Second, bone marrow mesenchymal stem cells (BMSCs) were isolated from healthy puppies and cultured with lipopolysaccharide (LPS) to observe how inflammation affects osteogenesis. Finally, the osteogenesis activity of BMSCs transfected with lentiviral vector either overexpressing (miR-146a-up) or inhibited for miR-146a expression was evaluated. miR-146a-up-transfected BMSCs were injected locally into the distraction gaps of the DO model canines. On days 42 and 56 post-surgery, the bone volume/tissue volume and bone mineral density values were evaluated via using micro-computed tomography, and newly formed tissues were harvested and evaluated via histological staining. The expression of miR-146a in both the DO canine model and LPS-stimulated BMSCs increased. Overexpression of miR-146a enhanced cell proliferation, migration, and osteogenic differentiation. Additionally, the newly formed callus was improved in canine mandibles injected with miR-146a-up-transfected BMSCs. In summary, miR-146a regulates mandibular DO by improving osteogenesis, and can serve as a potential target to shorten the therapy period of DO.     

Humoral mechanisms of regulation of reparative osteogenesis

The effect of the blood serum from animals with active osteogenesis on the biosynthesis of nucleic acids and protein and on mineralization of regenerating bone tissue was studied in experiments in vivo and in vitro. Incorporation of labeled precursors of DNA ([³H]thymidine) and protein ([¹⁴C]proline) in the recipients was intensified and mineralization of bony callus (incorporation of⁸⁵Sr) was accelerated. Comparison of the order of stimulation of nucleic acid and protein synthesis suggests that the active principle of the serum promotes more rapid cell proliferation in the fracture zone.Laboratory of Pathophysiology and Laboratory of Biochemistry, Research Institute of Experimental and Clinical Orthopedics and Traumatology, Kurgan. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Fedorov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 12, pp. 725–727, December, 1977.     

Prenatal diagnosis of perinatally lethal osteogenesis imperfecta

Prenatal diagnosis of osteogenesis imperfecta was achieved at 17 weeks of gestation using ultrasound through recognition of low echogenic properties of all the bones, abnormally shaped skull, bell-shaped rib cage, distally thinned ribs, short and deformed long bones, wide metaphyses, and thin diaphyses. Severely limited abnormal movements, abnormal positioning of the lower limbs also were typical of the condition. The recognition of the signs reported in this paper will allow the identification of the condition in utero in the second trimester.     

两种壳聚糖载rhBMP-2纳米微球对SD大鼠体内异位成骨的影响

目的　通过SD大鼠异位成骨实验来探究重组人骨形态发生蛋白-2/壳聚糖/硫酸葡聚糖(rhBMP-2/CS/DS) 复合微球和重组人骨形态发生蛋白-2/壳聚糖 (rhBMP-2/CS) 微球对SD大鼠体内异位成骨的影响。 方法　随机将36只SD大鼠平均分为三组（n=12）,分别为A组 (rhBMP-2), B组(rhBMP-2/CS), C组(rhBMP-2/CS/DS)。制备股四头肌肌袋模型后,分别将三种材料植入股四头肌肌袋肌间隙中。分别在4,8和12周时大体观察植入区组织硬度,每组处死4只大鼠后取出异位骨块,并切取异位骨化的组织行micro-CT扫描及 Mimics软件三维重建;检测各组织块骨体积分数（bone volume fraction,BVF）、骨小梁厚度（trabecular thichness,Tb.Th）、骨密度（bone mineral density,BMD）;并行组织学观察和ALP活性、钙含量检测。 结果 4周时,A、B、C三组植入区周围组织质地均稍硬,三者并无明显区别;8周和12周时,三组植入区硬度明显增加,且C组比A、B组质地更硬。4周时,HE染色可见三组有少量骨组织形成,但不明显;B、C两组BVF、Tb.Th、BMD,碱性磷酸酶（ALP）活性、钙含量均高于A组;B、C两组以上指标差异无统计学意义。8、12周时,HE染色可见到三组骨组织逐渐增多,并逐渐成熟,且B、C两组可见到比A组更成熟的骨组织,C组骨组织比B组更成熟;B、C两组BVF、Tb.Th、BMD,ALP活性、钙含量均高于A组,C组以上指标均高于B组。 结论　rhBMP-2/CS/DS纳米缓释微球的成骨效果明显强于rhBMP-2/CS纳米微球和单独rhBMP-2,其可能在骨组织工程领域有较好的运用前景。     

Psychosocial aspects of osteogenesis imperfecta: An update

Osteogenesis imperfecta (OI) is an inherited disorder in which affected individuals are stigmatized by virtue of physical differences from their peers. The extent to which these differences alter life style depend on the severity of the disorder, its natural history, the extent to which it affects social integration, the effect on physical appearance, and the presence of other affected family members. Some of these factors may adversely influence the ability of affected individuals to effectively adjust to their social and work environment and recognition of these factors may aid individuals and helpers in easing the path to a constructive life.     

Comprehensive rehabilitation of the child with osteogenesis imperfecta

Children with osteogenesis imperfecta (OI) that results in considerable deformity are often viewed as poor candidates for aggressive physical therapy and rehabilitation. To determine if this view is realistic, we have entered almost 50 children with OI type III and OI type IV into a comprehensive graduated rehabilitation program, based at the National Institutes of Health, but designed to be implemented by continuing involvement of community resources. Children are begun in the program early with emphasis on gain of head and trunk control and progression to sitting and walking, if possible, with the aid of a variety of phsysical supports, including internal and external bracing. Although not conducted in a randomized fashion, the program's success in bringing children into graded exercise regimes and fostering their increased involvement in school and social situations suggest that aggressive physical therpy and rehabilitation have a major place in the overall care of the infants and children with OI.     

Early surgical management of severe forms of osteogenesis imperfecta

The early surgical management of severe osteogenesis imperfecta (OI) was studied in three children with autosomal recessive type III form of this disease. Each child had similar clinical and radiographic features at birth. The spine, pelvis, and thorax were osteoporotic but were well formed and free of major fractures. In contrast, the peripheral skeleton was severely affected with numerous new and old fractures. Conservative treatment of fractures was undertaken with a foam mould for the torso and limbs and additional support was provided for specific unstable painful fractures. However, fractures continued due to the extreme bone fragility and deformities. Surgical correction of deformities and internal splinting of the long bones with intermedullary rods was commenced between 18 months and 5 years of age. The shafts of the long bones were extremely fragile and lacked cortical bone. The osteotomies were under-taken with a scalpel. The fracture rate diminished rapidly but the non-extending rods needed shortening or replacing within 2 to 3 years. The combination of external and internal fixation and electric wheel chairs greatly reduced the frequency of fractures and facilitated the general care and development of these 3 children with a severe form of OI.