股骨骨缺损动物模型制备现状及特点

背景：骨缺损的修复及后期临床转归仍是临床研究中的热点和难点,是困扰临床医师的常见问题。构建合适、可重复性及无限接近临床的动物实验模型及科学的评估对进一步的临床治疗相关疾病至关重要。目的：回顾性分析文献中股骨骨缺损常用实验动物模型制备方法及不同模型特点,评估优势与不足,为相关研究者选择合适的股骨骨缺损动物模型提供一定的参考。方法：检索PubMed、Web of Science、Medline数据库及CNKI数据库,设定英文检索词为：bone defect,bone,bones,defect,defects,defective,animal model,animal,model,laboratory,laboratory animal,animal laboratory;中文检索词为：骨缺损,动物模型,实验。检索时限为2000-01-01/2022-08-01。结果与结论：(1)对入选的27篇随机对照动物实验进行了分析和评估,实验动物包含大鼠、小鼠、新西兰兔及羊,骨缺损类型主要包含圆柱形骨缺损和节段性截骨骨缺损,部位以股骨中段及远端居多。多用于评估骨修复材料、药物、载药活性物质及物理治疗等...     

兔桡骨临界骨缺损模型的制备

背景：各种原因造成的骨折和骨缺损导致的骨不连一直是临床骨科修复的一大难题,相关产品质量的检验需要标准的骨缺损模型,然而骨缺损的临界长度至今仍无定论。 目的：建立兔桡骨骨缺损模型,以确定兔桡骨临界骨缺损长度。 方法：将18只雄性新西兰大白兔,随机分为6组,在双侧桡骨中段分别做12,13,14,15,16,17 mm的缺损,伤口缝合包扎但不固定。 结果与结论：大体标本和放射学观察显示,3个月内12,13,14,15,16 mm组的缺损均有修复完整的情况,但17 mm组无一例修复。组织学结果显示12,13,14,15,16 mm组缺损修复区有骨小梁与骨基质的形成、骨再生和再血管化、髓腔不同程度再通以及成骨细胞,17 mm组可见成骨细胞,破骨细胞,但未见骨再血管化和髓腔再通。故兔桡骨临界骨缺损长度为17 mm。     

幼龄兔及成年兔桡骨骨缺损模型中骨缺损大小的对比研究

目的 探讨不同月龄新西兰兔建立桡骨骨缺损模型时骨缺损大小的选择。方法 选取3月龄(幼龄兔)及6月龄(成年兔)健康雄性新西兰兔各20只,根据兔龄分为A组(3月龄)和B组(6月龄),每组兔前肢采用数字表法随机分为2亚组制备桡骨骨缺损模型,每组20侧。其中A1组、B1组桡骨骨缺损长度为15 mm,A2组、B2组骨缺损长度为20 mm。分别于模型制备术后第4、8、12周行X线检查,并应用X线Lane-Sandhu评分标准评估骨愈合情况。术后12周处死所有实验动物,取桡骨标本进行大体及组织学观察,分析骨愈合情况。结果 制备骨缺损模型术后,所有实验兔均存活。X线检查显示:术后第8周A1组骨缺损基本愈合,至第12周新生骨塑形完全,与正常桡骨形态类似;其余3组至第12周骨缺损均未完全修复,断端及邻近尺侧有少量新骨生成,髓腔封闭。术后各时间点X线Lane-Sandhu评分结果示:组内比较,A1组评分均高于A2组,差异均有统计学意义(P值均<0.05);B1组与B2组评分比较,差异均无统计学意义(P值均>0.05)。组间缺损尺寸相同的亚组间比较:A1组、A2组评分分别高于B1组、B2组,差异均有统计学意义(P值均<0.05)。术后12周标本大体观察显示:A1组断端形成骨性桥接,新生骨塑形良好,其余3组断端髓腔封闭,缺损区由纤维组织填充。组织学结果示A1组修复完全,新生骨骨板排列规则;其余3组缺损空腔可见纤维组织填充。结论 兔龄和骨缺损大小对于术后骨缺损愈合情况有重要影响,在构建兔桡骨骨缺损模型的动物实验中,幼龄兔(3月龄)骨缺损长度宜选择20 mm,成年兔(6月龄)宜选择15 mm。     

聚乳酸/矿化胶原复合人工骨修复材料在兔股骨髁松质骨缺损中的应用研究*

目的 研究聚乳酸/矿化胶原人工骨修复材料（NBG）在兔股骨髁松质骨缺损中的疗效,以及该材料与自体骨、骨髓混合使用的效果,考察材料的安全性及有效性。方法 在兔双侧股骨髁造成松质骨缺损,将60只雄性大白兔进行不同骨材料植入。试验分为5组：空白（Blank）组、人工骨（NBG）组、人工骨混骨髓（NBG+ABM）组、人工骨混自体骨（NBG+AGB）组、自体骨（AGB）组,通过影像学观察、组织学评价、生物力学分析等方法考察5 组材料的骨修复性能。结果 观察新生骨和周围骨质结合情况,拍摄X线片并进行灰度值分析以及进行CT三维重建分析,不同时间点的组织切片观察,均表明NBG组、NBG+ABM组、NBG+AGB组、AGB组骨修复效果良好,生物力学测试也表明各实验组相对于空白组可以承载较高的压力载荷。AGB组、NBG+AGB组、NBG+ABM组、NBG组修复效果依次降低,但均接近完全修复。结论 聚乳酸/矿化胶原基人工骨修复材料有良好的生物相容性及骨诱导性,是良好的骨植入材料。单独使用即可以获得良好的骨修复效果,也可以和自体骨或骨髓混合使用,修复效果更加明显。     

股骨近端骨肿瘤及瘤样病变骨缺损的修复重建

目的 探讨股骨近端骨肿瘤及瘤样病变骨缺损的修复重建方式.方法 对自1998～2003年共49例股骨近端骨肿瘤或瘤样病变的手术治疗及术后疗效进行回顾性分析,本组中17例采取病变刮除,瘤壁烧灼,自体、异种骨、人工骨或复合移植术;12例采取病变刮除,瘤壁烧灼或酒精浸泡,自体骨、异种骨、人工骨或复合骨移植,并辅予内固定固定术;20例采取瘤段切除,定制人工关节假体重建关节术;术后均获随访.结果 术后随访17～51个月,平均31个月,X线片可见缺损修复区内有骨降解和骨替代现象发生,2例复发,其中1例伴内固定物旁骨折,其余术后患肢功能恢复良好,4～12个月撤拐行走,无跛行;假体重建者1例假体断裂,1例死亡,根据Enneking术后功能评估系统,20例术后10～14月的评分73%～87%.结论 根据肿瘤生物学行为及股骨近端生物力学选择个体化的修复重建方式,对股骨近端骨肿瘤及瘤样病变的疗效满意.     

多孔丝素蛋白支架修复兔下颌骨临界性骨缺损

背景：丝素蛋白具有良好的生物相容性和可降解性。 目的：观察多孔丝素蛋白支架原位修复兔下颌骨临界性骨缺损效果。 方法：建立兔双侧下颌骨临界性骨缺损模型,随机选取一侧缺损植入多孔丝素蛋白支架作为实验组,另一侧缺损不作处理作为对照组。 结果与结论：①大体标本：术后12周,实验组骨缺损腔表面完全被新生骨覆盖,材料无脱出;对照组骨缺损腔内充满肉芽组织,骨不连。②X射线骨密度测定：术后2,6,12周,两组骨密度均随着时间延长逐渐增高,组内不同时间点间差异有显著性意义(P < 0.05),且同期实验组高于对照组(P < 0.05)。③组织病理切片苏木精-伊红染色：术后12周,实验组岛状新生骨及骨小梁明显增多,而且粗大而致密,材料内部明显疏松,部分区域塌陷;对照组宿主骨边缘可见散在分布的新生骨组织,但并无粗大骨小梁形成。④骨形态发生蛋白2免疫组织化学染色：术后2,6,12周,两组骨形态发生蛋白2阳性细胞数均随着时间延长逐渐增多,组内不同时间点间差异有显著性意义(P < 0.05),且同期实验组多于对照组 (P < 0.05)。表明多孔丝素蛋白支架用于原位组织工程修复骨缺损具有一定可行性。     

大动物节段性骨缺损模型的研究进展

四肢节段性骨缺损,尤其是临界尺寸节段性骨缺损的修复仍然是骨科最具挑战性的难题之一。人工骨材料逐渐取代自体骨及同种异体骨成为骨缺损修复的研究热点。为评价人工骨材料作为骨缺损修复替代物的发展前景,有必要建立可重复且有效的节段性骨缺损动物模型,但目前尚无一种理想的大动物节段性骨缺损模型能完美模拟人类骨结构和力学特征。因此本文对大动物节段性骨缺损模型的临界尺寸骨缺损大小的取值、常用建模动物的优缺点、节段性骨缺损模型的建立、骨材料的不同固定方法等方面进行综述,以促进大动物节段性骨缺损模型的优化改进。     

可注射矿化胶原水凝胶修复大鼠颅骨临界性骨缺损的研究

目的 基于矿化胶原（MC）与海藻酸盐（ALG）,制备一种新型可注射矿化胶原水凝胶（MCA）,研究MCA对颅骨临界性骨缺损的修复作用。方法 将MC粉末以200 mg/mL的比例加入到ALG（C_ALG=15 mg/mL）中制备出矿化胶原水凝胶（MCA）。采用扫描电子显微镜对MCA的交联状态和元素分析情况进行观察。采用L929细胞增殖实验评估MCA的生物安全性,体内降解实验观察MCA降解性和生物相容性。通过大鼠颅骨临界骨缺损模型来验证MCA的骨修复效果。结果 MCA水凝胶经过扫描电子显微镜（SEM）观察后发现水凝胶表面粗糙,其内部Ca/P信号均匀且密集。为了评估MCA的生物安全性,使用MCA浸提液与L929细胞共同孵育后,发现200 mg/mL浸提液实验组的L929细胞增值率为99.95%,毒性评级为1级。同时,将MCA水凝胶注射至大鼠皮下,术后60 d注射部位仍见残留的MCA植入物,而在MCA水凝胶注射到颅骨缺损处的第60天时,MCA则全部降解。最后,观察MCA在颅骨临界骨缺损动物模型中的骨缺损修复效果,实验结果表明MCA水凝胶组的颅骨缺损修复效果优于ALG水凝胶组和对照组。结论 MCA水凝胶具有良好的生物安全性,降解性和促进骨再生的能力,是一种安全可靠的骨修复材料。     

股骨内髁参数对单髁置换中截骨及假体设计的参考意义

BACKGROUND: Knee-parameter measurements play an important role in the designing of the knee prosthesis. Currently, we have more and more research of the total knee replacement, while uni-condylar knee replacement study is few.  OBJECTIVE: To obtain the parameters of the normal femoral condyles and explore its correlation with osteotomy and prosthesis design of the knee joint during uni-condylar knee replacement. METHODS: Normal knee joints of 60 cases (60 knees) were selected. We measured the parameters by using thin-section CT scan and post-processing techniques, including arc diameter of the lowest point of the femoral condyle on the coronal plane, arc diameter of the distal point of the posterior condyle of the femur on the transverse plane, arc diameter of the distal point of the posterior condyle of the femur on the sagittal plane, and arc diameter of the lowest point of the femoral condyle on the sagittal plane, and analyzed the correlation with sex and height.  RESULTS AND CONCLUSION: The diameter of the arc that passes through the lowest point of femoral medial condyle in the coronal plane was (42.685±1.389) mm. The diameter of the arc that passes through the farthest point of posterior of femoral medial condyle in the cross-section was (42.732±1.440) mm. The diameter of the arc that passes through the lowest point of femoral medial condyle on the sagittal plane was (45.473±1.332) mm. The diameter of the arc that passes through the farthest point of posterior of femoral medial condyle on the sagittal plane was (42.587±1.446) mm. The results illustrate that knee condyle related parameters were positively correlated with height. Parameters in males were significantly greater than in females. The diameter of the arc that passes through the lowest point of femoral medial condyle on the sagittal plane was significantly larger than that of the farthest point of femoral posterior medial condyle on the sagittal plane (P < 0.001). There was no significant difference among the diameter of the arc that passes through the lowest point of femoral medial condyle on the coronal plane, the diameter of the arc that passes through the farthest point of posterior of femoral medial condyle on the cross-section and that of the farthest point of femoral posterior medial condyle on the sagittal plane.       

股骨髁 X 线测量及性别判别分析

目的为积累资料和探讨国人股骨髁的性别差异，方法随机对 33～76 岁 194 例健康人(男 138，女 56)拍摄膝部正侧位 X 线片；在正位片上测量了上髁宽和内、外侧髁宽，在侧位片上测量了内、外侧髁长和高。用 SPSS 软件计算出 5 个指数和 7 个性别判别分析式。结果所测 7 项均具有非常显著的性别差异(t＝3．53～13．94，P＜0．01)，5 项指数除髁高指数外，均无显著性性别差异；7 个性别判别式的回代判别率在 75．45％～89．73％间。结论股骨髁的 X 线测量对性别判别具有一定的实用意义。     

Establishment and effects of allograft and synthetic bone graft substitute treatment of a critical size metaphyseal bone defect model in the sheep femur

Assessment of bone graft material efficacy is difficult in humans, since invasive methods like staged CT scans or biopsies are ethically unjustifiable. Therefore, we developed a novel large animal model for the verification of a potential transformation of synthetic bone graft substitutes into vital bone. The model combines multiple imaging methods with corresponding histology in standardized critical sized cancellous bone defect. Cylindrical bone voids (10 ml) were created in the medial femoral condyles of both hind legs (first surgery at right hind leg, second surgery 3 months later at left hind leg) in three merino‐wool sheep and either (i) left empty, filled with (ii) cancellous allograft bone or (iii) a synthetic, gentamicin eluting bone graft substitute. All samples were analysed with radiographs, MRI, μCT, DEXA and histology after sacrifice at 6 months. Unfilled defects only showed ingrowth of fibrous tissue, whereas good integration of the cancellous graft was seen in the allograft group. The bone graft substitute showed centripetal biodegradation and new trabecular bone formation in the periphery of the void as early as 3 months. μCT gave excellent insight into the structural changes within the defects, particularly progressive allograft incorporation and the bone graft substitute biodegradation process. MRI completed the picture by clearly visualizing soft tissue ingrowth into unfilled bone voids and presence of fluid collections. Histology was essential for verification of trabecular bone and osteoid formation. Conventional radiographs and DEXA could not differentiate details of the ongoing transformation process. This model appears well suited for detailed in vivo and ex vivo evaluation of bone graft substitute behaviour within large bone defects.     

改良"叉"形钢板固定股骨髁部C1型骨折的生物力学评价

目的 :评价改良“叉”形钢板对股骨髁部C1型骨折固定的生物力学性能。方法 :18具新鲜股骨下段及胫骨上段标本随机分成 3组 ,均制成股骨髁部C1型骨折模型 ,A组 :用改良“叉”形钢板固定 ;B组 :用股骨塑形钢板固定 ;C组 :用GSH钉固定。分别在MTS试验机上进行纵向压缩试验和轴向扭转试验 ,测量标本的纵向压缩位移、横向分离位移和扭转角度。结果 :改良“叉”形钢板、GSH钉、股骨塑形钢板固定组的纵向压缩位移分别为 (0 .41± 0 .0 3 )、(0 .3 8± 0 .0 1)、(0 .81± 0 .10 )mm ;横向分离位移分别为 (0 .2 0± 0 .0 1)、(0 .19± 0 .0 1)、(0 .3 0± 0 .0 1)mm ;扭转角度为 1.62°± 0 .0 7° ,1.69°± 0 .0 6° ,4.2 6°± 0 .72°。改良“叉”形钢板和GSH钉固定明显优于股骨塑形钢板 ,具有显著性差异 (P <0 .0 1)。结论 :改良“叉”形钢板用于固定股骨髁部C1型骨折 ,具有良好的生物力学性能 ,是治疗股骨髁部C1型骨折的一种较理想的内固定器械。     

高强度聚焦超声制备兔股骨头坏死模型的可行性研究

目的:探讨高强度聚焦超声新方法制备兔股骨头坏死模型的可行性。方法:采用JC200型聚焦超声治疗系统,以80 w/cm~2强度超声照射家兔双侧股骨头,分别于照射后1、7、14、21 d取材,结合股骨头大体形态和组织石蜡切片H-E染色观察股骨头坏死情况。结果:股骨头外观7 d时可见界限明显的白色坏死区,表面光泽度稍下降;14 d时坏死区表面软骨变黄、皱缩;21 d时囊化、易剥脱。镜下见1 d时坏死区表面软骨可见少量软骨细胞核溶解,髓质可见小静脉扩张充血、血窦充血;7 d时坏死区表面软骨轻微挤压皱缩,软骨下区见骨小粱断裂和空骨陷窝,髓质造血组织明显减少,骨小梁表面成骨细胞消失,坏死骨小梁附近增生纤维组织,出现脂肪小囊,骺板稍变形;14 d时兔股骨头表面软骨变薄,偶可见破损,坏死软骨细胞增多,表面破损程度、骺板变形程度较7 d时加重,修复区可见增生肉芽组织和新生血管,有纤维组织附着于坏死骨小梁;21 d时,股骨头表面软骨破损严重,骺板进一步扭曲变形,坏死区骨小梁破碎、消失,修复区可见纤维组织包绕坏死骨小梁和新生骨小梁。结论:高强度聚焦超声制备的兔股骨头坏死模型效果稳定,具有清晰的病理演变特征,可作为一种制备股骨头坏死模型的新方法。     

An overview: Rabbit hepatitis E virus (HEV) and rabbit providing an animal model for HEV study

Hepatitis E virus (HEV) is a single‐stranded, positive‐sense RNA virus and the causative agent of hepatitis E. The virus belongs to genus Orthohepevirus in the family Hepeviridae, which contains 4 major genotypes closely relating to humans. Genotypes 1 and 2 only infect humans whereas genotypes 3 and 4 HEV are harbored in a wide range of animal species worldwide and are zoonotic to humans. Recently, a novel animal strain of HEV has been isolated in farmed rabbits in China, and subsequently more strains were discovered in the rabbit populations in at least 7 other countries. Due to high sequence similarity to genotype 3 HEV, rabbit HEV (rHEV) has been assigned to genotype 3. Experimental study showed that rHEV could infect non‐human primate and human, which pose a direct threat to human. Further pathogenesis studies showed laboratory rabbits infected with rHEV and genotype 4 HEV could present similar signs of acute and chronic hepatitis E along with extra‐hepatic replication as observed in humans. High mortality and vertical transmission were reproduced in rHEV infected pregnant rabbits. Furthermore, rabbit model was also found suitable for evaluating HEV vaccine efficacy in order to manage zoonotic transmission. These data showed laboratory rabbits could serve as an alternative animal model for HEV study under the current circumstances that HEV propagation is limited in vitro. In general, this review aims at presenting comprehensive up‐to‐date information about rHEV strains and rabbit model for HEV studies.     

69例股骨髁骨折的手术治疗分析

目的探讨手术治疗股骨髁部骨折的临床效果。方法对我院2009年9月至2011年9月收治的69例股骨髁部骨折患者手术后的临床资料进行回顾性分析,了解患者手术治疗后随访情况,评估患者术后骨折愈合和关节活动恢复效果。结果对所有患者随访6-18个月,按照Kolmenrt评定标准对临床疗效进行判定,其中评分为优48例（69．57％）,良17例（24．64％）、一般3例（4．35％）、差1例（1．44％）,优良率为94．21％。结论手术治疗股骨髁骨折疗效肯定,并发症少,骨折愈合较好,总体疗效令人满意。     

Bone regeneration and infiltration of an anisotropic composite scaffold: an experimental study of rabbit cranial defect repair

Tissue formation on scaffold outer edges after implantation may restrict cell infiltration and mass transfer to/from the scaffold center due to insufficient interconnectivity, leading to incidence of a necrotic core. Herein, a nano-hydroxyapatite/polyamide66 (n-HA/PA66) anisotropic scaffold with axially aligned channels was prepared with the aim to enhance pore interconnectivity. Bone tissue regeneration and infiltration inside of scaffold were assessed by rabbit cranial defect repair experiments. The amount of newly formed bone inside of anisotropic scaffold was much higher than isotropic scaffold, e.g., after 12 weeks, the new bone volume in the inner pores was greater in the anisotropic scaffolds (>50%) than the isotropic scaffolds (<30%). The results suggested that anisotropic scaffolds could accelerate the inducement of bone ingrowth into the inner pores in the non-load-bearing bone defects compared to isotropic scaffolds. Thus, anisotropic scaffolds hold promise for the application in bone tissue engineering.