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1.
可降解多孔β—TCP/rhBMP—2人工骨的骨诱导活性研究   总被引:11,自引:1,他引:10  
王丹  郑昌琼 《中华骨科杂志》1998,18(11):689-691,I003
目的:检测可降解多孔β-TCP/rhBMP-2人工骨的诱导成骨能力。方法:自制要降解多孔β-TCP与rhBMP-2复合后植入45只小鼠股后肌袋作为实验组,单纯β-TCP植入对侧作对照,术后24,72小时,1,2,4,8周分别取材做组织学检查,2,4周取材的部分标本做扫描电镜观察:1,2,4周取材的部分标本做碱性磷酸酶(ALP)活性测定。结果:实验组有大量新生软骨和骨形成,随着时间的推移,生成量逐渐  相似文献   

2.
随着分子生物学的发展,多种生长因子参与骨和软骨的生成过程逐渐为人们所认识。骨形态发生蛋白(BMP)为一种诱导成骨因子,目前已能利用基因工程获得具有生物活性的rhBMP2〔1〕,体外和体内实验均证明rhBMP2〔1〕有明显骨诱导活性〔2〕。它能诱导...  相似文献   

3.
陶瓷样异种骨复合骨髓异位成骨的实验研究   总被引:14,自引:3,他引:11  
目的了解陶瓷样异种骨(CXB)与骨髓(BM)复合移植的成骨作用。方法将CXB与BM复合及单纯CXB植入兔的骶棘肌内,术后2、4、8、12、16及24周取出植入材料作组织学及组织化学检查,观察植入材料的成骨作用。结果CXB与BM复合植入后2周开始有软骨和新骨生成,以后软骨逐渐钙化成骨,8周时出现髓腔,并随植入时间的延长,新骨生成增多,成骨更为典型。而单纯CXB植入后无新骨或软骨形成。结论CXB与BM复合移植通过骨传导、骨诱导及提供成骨细胞或成软骨细胞而成骨,是一种理想的骨移植替代材料,可望在临床上用于骨缺损的修复。  相似文献   

4.
重组人骨形态发生蛋白-2诱导成骨作用的动物实验研究   总被引:1,自引:0,他引:1  
骨形态发生蛋白(bonemorphogeneticprotein,BMP)的主要作用和用途是诱导新骨形成和促进骨损伤的修复。作者采用多种动物模型,观察了大肠杆菌表达的重组人BMP—2(rhBMP—2)的生物学作用。小鼠股部肌肉内植入试验结果表明,rhBMP—2具有较强的诱导成骨活性。植入后第21天,局部有硬质骨的形成,新生骨有骨皮质和不规则的骨髓腔,植入区局部的股骨增粗,股骨重量明显增加。组织形态学观察表明,诱导成骨过程符合典型的软骨内成骨的时相。另在大鼠颅骨大面积缺损模型中观察到,在颅骨缺损区植人rhBMP—2三个月后,缺损区内有从周边向中央生长的新骨生成,实验组缺损区的面积明显小于对照组,并且颅骨的厚度也显著增加。家兔股骨骨膜下植入试验发现,rhBMP—2植入后21天,植入区股骨的骨皮质增厚,并有沿骨干延伸的骨痂组织的产生。以上结果证明,大肠杆菌表达的重组人BMP—2有较强的跨种诱导成骨活性和骨损伤修复作用,具有较好的临床应用前景。  相似文献   

5.
多孔β—TCP/BMP复合人工骨的研制和动物体内的相关研究   总被引:23,自引:1,他引:22  
梁戈  胡蕴玉 《中华骨科杂志》1998,18(2):75-79,I003
多数人工骨缺损修复材料无骨诱导活性,为使人工植骨材料具有骨诱导活性并可在体内降解,本研究采用可降解陶瓷β-磷酸三钙(β-TCP)与骨形成蛋白(BMP)复合形成具有骨诱导能力的人工骨。将β-TCP/BMP、单纯TCP、羟基磷灰石(HA)和TCP/HA分别植入168只小鼠股部肌肉内,在24、72小时,1、2、4、8周取材,作大体观察、组织形态学观察、扫描电镜观察及碱性磷酸酶(ALP)检测。另将上述材料植入55只兔桡骨1.5cm缺损中,分别在2、4、8、12、16周取材,作大体、X线、组织形态学观察及计算机图像分析。研究结果显示:将β-TCP/BMP植入小鼠肌袋后1周软骨生成,4周有造血骨髓的板层骨生成。ALP检测1、2周水平最高。植入材料与骨组织之间无纤维组织间隔。在兔桡骨缺损修复的研究中发现,β-TCP/BMP的骨缺损修复作用最强,16周植入材料的降解达53%,成骨量亦最多。研究结果表明:β-TCP/BMP是一种可降解、具有较强骨诱导能力、生物相容性较好的人工骨。  相似文献   

6.
重组人骨形态发生蛋白—2诱导成骨作用的动物实验研究   总被引:7,自引:1,他引:7  
刘莉  赵明 《中华骨科杂志》1995,15(8):519-522
骨形态发生蛋白(bone morphogenetic protein,BMP)的主要作用和用途是诱导新骨形成和促进骨损伤的修复。作用采用多种动物模型,观察了大肠杆菌表达的重组人BMP-2(rhBMP-2)的生物学作用。小鼠股部肌肉内植入试验结果表明,rhBMP-2具有较强的诱导成骨活性。植入后第21天,局部有硬有的形成,新生骨有骨皮质和不规则的骨髓腔,植入区局部的股骨增粗,股骨重量明显增加。组织形  相似文献   

7.
目的:对bFGF增强rhBMP-2诱导成骨的调节机理进行探讨。方法:210只BALB/c小鼠随机分为3组,每组70只,试验侧均位于右后肢。设立rhBMP-2/牛松质骨载体、单纯牛松质骨载体为对照组,分别于术后12h~21d共11个时间点取材,观察其诱导成骨过程。结果:rhBMP-2/bFGF/聚乙烯吡咯啉酮/牛松质骨载体组在诱导间充质细胞增殖、分化,软骨细胞、新生骨形成方面均早于rhBMP-2/牛松质骨载体组,成骨量优于rhBMP-2/牛松质骨载体组,而单纯牛松质骨载体组在21d仅出现了少量增殖的间充质细胞。结论:rhBMP-2和bFGF在诱导成骨调节中存在着协同作用。  相似文献   

8.
目的 比较三种重组合人工骨的成骨能力。方法 在50 只兔的100 个颅骨缺损动物模型中分别植入:①牛脱蛋白骨(b D P B)/牛骨形态发生蛋白(b B M P)/肿瘤坏死因子α( T N Fα);②b D P B/b B M P/碱性成纤维细胞生长因子(b F G F);③b D P B/b B M P/表皮细胞生长因子( E G F);④b D P B/b B M P。植入后1、2、4、6 及8 周行组织学检查及 X 线摄片; 植入后10 及42 天行 35 S和45 Ca 液闪计数及灰重测定。结果 成骨能力:b D P B/b B M P/ T N Fα> b D P B/b B M P/b F G F( P< 0.01) > b D P B/b B M P/ E G F( P< 0.01);b D P B/b B M P/ E G F 与 b D P B/b B M P 无显著性差异( P> 0.05)。结论  T N Fα与 B M P及载体复合后,在体内对骨修复产生明显的促进作用,在载体/骨诱导因子/生长因子的重组合人工骨模式中, D P B/b B M P/ T N Fα是一种有价值的骨移植材料。  相似文献   

9.
目的 探讨复合基因重组人BMP2 的异种骨(rhBMP2/BCB) 移植及其与骨膜联合移植修复节段性骨缺损的效果。方法 将rhBMP2 与去抗原牛松质骨载体(BCB)复合,制成rhBMP2/BCB;并采用兔桡骨干1.5 cm 缺损的动物模型,通过X线、生物力学、骨密度、组织学等检测手段,比较单纯rhBMP2/BCB移植、rhBMP2/BCB 与带血运骨膜联合移植及rhBMP2/BCB 与游离骨膜联合移植修复节段性骨缺损的疗效。结果 (1) 单纯rhBMP2/BCB 移植,可在16 周使节段性骨缺损基本修复,其修复机制与过程和重组异种骨相似;(2)rhBMP2/BCB与带血运骨膜联合移植,8 周即可修复骨缺损,其修复机制与骨折修复相仿,包括膜内成骨和软骨成骨两种机制;(3)rhBMP2/BCB与游离骨膜联合移植,在骨缺损修复早期( ≤12 周) ,其成骨速度及成骨质与量均优于单纯rhBMP2/BCB移植,约在12 周使骨缺损基本修复。结论 上述三种方法均可有效地修复节段性骨缺损,但以rhBMP2/BCB与带血运骨膜联合移植较为理想。该方法同时具有良好的骨生成、骨传导和骨诱导作用。  相似文献   

10.
目的:对bFGF增强rhBMP-2诱导成骨的调节机理进行探讨。方法:210只BALB/c小鼠随机分为3组,每组70只,试验侧均位于右后肢。设立rhBMP-2/牛松质骨载体、单纯牛松质骨载体为对对照组,分别于术后12h~21d共11个时间点取材,观察其诱导成骨过程。结果:rhBMP-2/bFGF/聚乙烯吡咯啉酮/牛松质骨载体组在诱导间充质细胞增殖、分化,软骨细胞、新生骨形成方面均早于rhBMP-2/  相似文献   

11.
目的 评价重组人骨形成蛋白 - 2 (rh BMP- 2 )与胶原复合物在大鼠颅骨表面的成骨作用。方法 用 SD大鼠 9只在两侧颞部各制备一骨膜下袋后 ,分为实验侧和对照侧。右侧植入 rh BMP- 2与胶原复合物为实验侧 ,左侧植入单纯胶原作为对照 ,分别于术后 2、4及 8周处死动物各 3只 ,取标本制作脱钙石蜡切片 ,观察成骨情况 ,并测量成骨厚度。结果  rh BMP- 2与胶原复合物可在颞骨表面通过膜内成骨的方式诱导新骨形成 ,并与颞骨外板良好结合 ,术后 2周 ,植入物大部分降解吸收 ,颞骨表面有大量新生骨 ;术后 4周 ,植入物完全为新骨代替 ,颞骨厚度约为厚原度的 5倍 ;术后 8周 ,新骨更加成熟 ,颞骨厚度约为原厚度 2 .8倍。而对照侧骨质在术后各周均无明显增厚。结论  rh BMP- 2与胶原复合物可作为良好的表面植骨替代材料 ,并能与植骨床良好结合  相似文献   

12.
目的:制备多孔复合材料明胶微球/rhBMp-2/CPC并研究其异位成骨效应。方法:双相乳化冷凝聚合法制备明胶微球,京尼平进行交联,喷金后电镜观察。交联微球携载rhBMP-2,以2.5%的比例掺入磷酸钙骨水泥(calcium phosphate cements,CPC)固化,制成实验用多孔明胶微球/rhBMP-2/CPC,rhBMP-2/CPC作为对照组.两组材料固化后分别浸入生理盐水,1、3周后进行生物力学压缩实验,扫描电镜观察材料断面:ELISA法测定不同时间点生理盐水中rhBMP-2浓度,计算rhBMP-2的累积释放量。材料植入小鼠大腿肌袋,术后3周处死小鼠,切取材料及周围组织,HE染色后进行组织学观察,同时测定材料周围组织中碱性磷酸酶及钙含量。结果:交联的明胶微球呈规则圆形,粒径(62±18)um,分散性好。1、3周后实验组材料断面可见大量大孔形成,对照组未见明显大孔,实验组的总孔径率、大孔率及rhBMP-2的累积释放量均高于对照组:3周后实验组最大压缩强度(7.8±1.2)MPa,较对照组(11.2±1.6)MPa稍低。HE染色两组均可见软骨形成,但实验组更多,碱性磷酸酶及钙含量测定实验组分别为(4.33±0.52)IU/g和(6.12±1.22)ug/mg,高于对照组的(2.67±0.23)IU/g和(3.12±0.41)ug/mg。结论:明胶微球/rhBMp-2/CPC在微球降解后形成多孔磷酸钙复合材料,使rhBMp2的释放量增加,具有强大的异位成骨性能,是一种优秀的骨组织工程材料。  相似文献   

13.
An ideal artificial substitute has good biocompatibility properties and is able to provide for rapid bone formation. Bone morphogenetic protein‐2 (BMP‐2) is considered as one of the most important growth factors for bone regeneration. In this study, a synthetic BMP‐2‐related peptide (designated P24) corresponding to residues of the knuckle epitope of BMP‐2 was introduced into a bioactive scaffold based on nano‐hydroxyapatite/collagen/poly(L ‐lactic acid) (nHAC/PLLA); its in vitro release kinetics was then measured. A 5 mm diameter cranial bone defect was created in the calvariae of 30 rats and randomly implanted with three groups of biomaterials: Group A (nHAC/PLLA alone); Group B (P24/nHAC/PLLA composite); and Group C (recombinant human BMP‐2 (rhBMP‐2)/nHAC/PLLA composite). The P24/nHAC/PLLA implants significantly stimulated bone growth similarly to the rhBMP‐2/nHAC/PLLA implants based on the radiographic and three‐dimensional CT evaluation and histological examination, thereby confirming the enhanced bone healing rate of these compounds compared with the stand‐alone nHAC/PLLA scaffold material. The osteoinductive ability of 3 mg P24 was similar to that of 1 µg rhBMP‐2. P24/nHAC/PLLA is a promising scaffold biomaterial for bone tissue regeneration. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1745–1752, 2011  相似文献   

14.
H Itoh  S Ebara  M Kamimura  Y Tateiwa  T Kinoshita  Y Yuzawa  K Takaoka 《Spine》1999,24(14):1402-1405
STUDY DESIGN: Posterolateral lumbar spinal fusion with use of recombinant human bone morphogenetic protein 2 (rhBMP-2) was tested in rabbits by implanting composites of rhBMP-2 and collagen carrier. OBJECTIVES: To examine the bone-formation-inducing activity of rhBMP-2 and find the optimal amount of rhBMP to add to a collagen carrier to constitute bone-formation-inducing implants to be substituted for bone graft in posterolateral spinal fusion in rabbits. SUMMARY OF BACKGROUND DATA: In animal models, rhBMP-2--impregnated collagen has been successfully used for posterolateral spinal fusion, indicating that it is a potential substitute for the autogenous corticocancellous bone graft currently used most routinely in posterolateral lumbar spinal fusion. METHODS: Nine rabbits were divided into three equal groups. The bilateral L4-L5 transverse processes were exposed, and collagen strips impregnated with rhBMP-2 (10, 50, or 200 micrograms) were placed on the left transverse processes, and collagen strips alone were inserted on the right. All rabbits were killed 24 weeks after surgery. The implanted sites were assessed for new bone formation and bony fusion by radiography and histologic examination. RESULTS: New bone formation was noted in intertransverse spaces on the left side of all rabbits except one (10 micrograms rhBMP-2). Twelve weeks after implantation, no new bone formation was seen on the right side of all animals. The newly formed bone masses were significantly larger in the 50-microgram and 200-microgram rhBMP-2 groups than in the 10-microgram rhBMP-2 group (P < 0.01), but there was no significant difference between bone formation in the 50-microgram and 200-microgram groups (P = 0.647). CONCLUSIONS: The rhBMP-2/collagen composite implant was an effective bone graft substitute for achieving posterolateral spinal fusion. When combined with a collagen carrier, the optimal rhBMP-2 dose for achieving posterolateral spinal fusion seemed to be approximately 50 micrograms per segment in rabbits.  相似文献   

15.
Objective: To investigate the effect of nanohydroxyapatite/collagen (nHA/collagen) composite as a graft extender and enhancer when combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) on lumbar intertransverse fusion in rabbits. Methods: Sixty-four adult female New Zealand white rabbits, aged 1 year and weighing 3.5-4.5kg, underwent similar posterolateral intertransverse process arthrodesis and were randomly divided into 4 groups based on different grafts: autogenous cancellous bone alone (ACB group), nHA/collagen alone ( HAC group ), half autogenous cancellous bone and half nHA/collagen (ACB HAC group) and nHA/collagen combined with rhBMP-2 (HAC BMP group ). The fusion masses were analyzed by manual palpation, radiography, biomechanical testing and histological examination. Results: Fusion was observed in 4 cases in the 6th week and in 5 cases in the 10tb week after surgery in ACB group. No case showed fusion in HAC group. In ACB HAC group, there was fusion in 3 cases in the 6th week and in 4 cases in the 10th week after surgery. In HAC BMP group, fusion in 1 case was found in the 4th week, in 5 cases in the 6th week and in 6 cases in the 10th week after surgery. It suggested that ACB, ACB HAC and HAC BMP groups showed similar fusion ratio and mechanical strength in the 6th and 10th week after surgery. According to the microstructure analysis of the samples, nHA/collagen had no negative effect when implanted together with ilium autograft. In HAC BMP group, new bone-like tissue was observed in the 2nd week postoperatively, and nearly all of the implanted composites were replaced by mature bone matrix and new bones in 10th week postoperatively. Conclusions:The nHA/collagen, especially combined with rhBMP-2, is a promising bone substitute, for it has quick biodegradation, fine bone-bending ability, and high osteoconductivity on posterolateral spinal fusion in rabbits.  相似文献   

16.
人骨髓基质细胞接种珊瑚构建组织工程骨   总被引:3,自引:1,他引:3  
目的:观察体外培养的人骨髓基质细胞与珊瑚复合物植入体内后的成骨能力。方法:穿刺抽吸入髂骨区骨髓基质细胞,体外培养扩增、诱导,将其与珊瑚复合后植入裸鼠体内,以单纯珊瑚作为对照。术后4、8周取材,通过大体、组织学、扫描电镜观察植入物体内成骨情况。结果:术后4周,复合物中有少量新骨形成;术后8周,复合物中出现大量成熟骨组织。而对照组无骨组织形成。结论:人骨髓基质细胞复合珊瑚在无免疫动物体内具有成骨能力,穿刺抽吸的人骨髓基质细胞可作为骨组织工程的种子细胞。  相似文献   

17.
目的观察重组人骨形态发生蛋白2/脱细胞骨基质材料(rhBMP2/ACBM)对体外培养的骨髓基质细胞(MSCs)增殖和分化的影响及兔桡骨骨缺损的修复作用。方法在制备rhBMP2/ACBM复合缓释载体的基础上,取培养第3代MSCs种植到材料上,体外培养4~7d,观察MSCs的增殖及碱性磷酸酶(AKP)、骨钙素的表达;将自体MSCs材料复合培养后24h回植到骨缺损局部,同期观察复合材料及空白对照组,分别于4、8、12周,通过X线、单光子放射计算机断层显象术(SPECT)、及组织学方法评价其对骨缺损的修复效果。结果与单纯体外培养组比较,复合载体在体外对MSCs具有成骨细胞诱导作用,而对细胞增殖无影响。与复合载体植入组比较,细胞材料复合植入组,4周时成骨量明显增多(P<0.05),且12周新骨塑型好。结论复合载体具有良好的体内外诱导成骨作用,细胞载体复合植入对骨缺损修复效果良好。  相似文献   

18.
目的 研究柠檬酸钙与骨形态发生蛋白-2(BMP-2)复合后成骨的作用.方法 取2月龄雄性昆明小鼠15只,通过体外实验获取柠檬酸钙与BMP-2最佳比例,在体外将10 mg柠檬酸钙与2mg BMP-2复合后,植入小鼠股部肌肉上中,行肌袋实验.以柠檬酸钙与BMP-2复合物为实验组,单独BMP-2为对照组,术后2、4、6周取材进行大体标本观察与组织学观察,计算新骨形成面积比及新生骨密度比.结果 大体标本观察与组织学观察示实验组成骨明显高于对照组,成骨面积较对照组明显增多.2、4、6周时比较差异均有统计学意义(P<0.05);2、4、6周时骨密度测量实验组较对照组高,差异均有统计学意义(P<0.05).实验组骨质2周时出现骨小梁结构,成熟度高,成骨细胞数量多,分化明显,成骨密度高;4周时骨的成熟度增高,更多粉红色骨质形成,骨质基本成熟,骨小梁增粗增大,出现大面积成骨区域;6周时血管化及骨髓腔形成充分,骨质密度高.结论 柠檬酸钙与BMP-2复合后具有良好的诱导成骨作用,可促进骨形成,是一种较理想的载体材料,可作为一种新型复合人工骨修复骨缺损.  相似文献   

19.
目的 对碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)增强重组人骨形态发生蛋白-2(recombinant human bone morphogenetic protein-2,rhBMP-2)诱导成骨能力的剂量依赖性进行研究。方法280只BALB/c小鼠随机分为8组,每组35只,实验组rhBMP-2的剂量均为0.5mg,bFGF的剂量分别为0、2、10、40、80、300、500活性单位(IU);设立单纯牛松质骨载体组为对照组。按实验设计,分别将rhBMP-2混悬液及bFGF-PVP溶液与牛松质骨载体充分混匀,负压下真空抽吸,冻干。将复合植骨材料植入小鼠右侧股部肌袋内,各组分别于术后第3、5、7、9、14、21d六个时间点取材,进行组织学、X线分析以及钙含量测定,观察各组的诱导成骨情况。结果(1)bFGF剂量为10~80IU时,间充质细胞增殖、分化,软骨细胞及新生骨形成均早于其它各组,成骨量多于其它各组,组织钙含量明显高于其它各组(P<0.05),提示此剂量bFGF使rhBMP-2的诱导成骨能力明显增强。(2)bFGF剂量为0.2、300 IU时,各组在间充质细胞增殖、分化,软骨细胞及新生骨形成以及组织钙含量方面差异均无显著性意义(P>0.05),提示此剂量bhBMP-2的诱导成骨能力无明显影响。(3)bFGF剂量为500IU时,术后第21d,仅1例标本可见散在的极少量新骨形成,其组织钙含量明显低于其  相似文献   

20.
The use of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) in spine fusion has led to concerns regarding a potential accompanying inflammatory response. This study evaluates a combination therapy (TrioMatrix®; Pioneer Surgical, Inc., Marquette, MI) comprised of a demineralized bone matrix (DBM), hydroxyapatite, and a nanofiber‐based collagen scaffold in a rodent spine fusion model. Thirty‐six athymic rats that underwent a posterolateral intertransverse spinal fusion were randomly assigned to 1 of 5 treatment groups: absorbable collagen sponge alone (ACS, negative control), 10 µg rhBMP‐2 on ACS (positive control), TrioMatrix®, Grafton® (Osteotech, Inc., Eatontown, NJ), and DBX® (Synthes, Inc., West Chester, PA). Both TrioMatrix® and rhBMP‐2‐treated animals demonstrated 100% fusion rates as graded by manual palpation scores 8 weeks after implantation. This rate was significantly greater than those of the ACS, Grafton®, and DBX® groups. Notably, the use of TrioMatrix® as evaluated by microCT quantification led to a greater fusion mass volume when compared to all other groups, including the rhBMP‐2 group. T2‐weighted axial MRI images of the fusion bed demonstrated a significant host response associated with a large fluid collection with the use of rhBMP‐2; this response was significantly reduced with the use of TrioMatrix®. Our results therefore demonstrate that a nanocomposite therapy represents a promising, cost‐effective bone graft substitute that could be useful in spine fusions where BMP‐2 is contraindicated. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1812–1819, 2011  相似文献   

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