压缩冲击对骨形成蛋白2基因修饰的组织工程骨的影响

目的观察直接压缩冲击对骨形成蛋白2(bone morphogenetic protein 2,BMP-2)基因修饰的组织工程骨细胞存活和成骨的影响,以探讨组织工程骨压缩植骨的可行性.方法体外培养扩增犬骨髓基质干细胞(marrow stromal stem cells,MSCs)转染腺病毒介导的人BMP-2(adenovirus mediated human BMP-2,Adv-hBMP-2)基因,与颗粒状的犬异体冻干松质骨复合.复合后4 d进行模拟压缩实验,分别于复合后24 h、4 d,压缩后即刻、1、4 d以扫描电镜观察细胞形态及数量.将单纯冻干骨、未经压缩的Adv-hBMP-2基因修饰的组织工程骨和压缩后4 d的Adv-hBMP 2基因修饰的组织工程骨植入裸鼠背部皮下,于术后6周行组织学观察新骨形成及冻干骨吸收情况.结果复合24 h冻干骨表面细胞展开,部分孔隙可见单层细胞生长;4 d后冻干骨表面细胞复层生长,胶原量多;压缩后即刻,冻干骨与冲击器接触的外表面基本无细胞存在,剖开面可见细胞片状掀起,碎片多;压缩后1 d,冻干骨表面细胞大部分脱落掀起,形成较多的细胞碎片;4 d后细胞数量明显减少,胶原分泌量增多.植入裸鼠背部皮下后,单纯冻干骨新骨形成极少,孔隙内主要为纤维组织,未经压缩的Adv-hBMP-2基因的组织工程骨组可见大量新骨形成,材料中心与周围新骨分布均匀,压缩后的Adv-hBMP-2基因的组织工程骨组新骨量明显减少,且主要在外周.结论体外模拟压缩植骨可明显减少基因修饰的组织工程骨中的细胞存活及体内成骨,但存活细胞的功能仍存在,可适用于压缩植骨重建假体周围骨缺损.     

非骨水泥长柄假体结合同种异体颗粒骨植骨在股骨翻修骨缺损重建中的应用

目的 回顾性分析股骨髓内同种异体颗粒骨打压植骨结合非骨水泥长柄假体在髋关节翻修术中股骨侧骨缺损修复应用的近期临床效果.方法 2003年7月至2009年6月对27例股骨侧骨缺损患者采用同种异体颗粒骨打压植骨,其中男性15例,女性12例,年龄47～78岁,平均67岁.失败原因:骨溶解、无菌性松动20例,全髋关节置换术后假体周围感染二期翻修7例.按Paprosky分型标准,Ⅱ型骨缺损3例,Ⅲ型骨缺损2l例,Ⅳ型骨缺损3例.术中均采用同种异体颗粒骨打压植骨、非骨水泥翻修柄植入.定期随访复查,包括临床、影像学评估,观察假体有无松动、下沉,植入骨活化替代情况以及假体周围骨折等并发症.Harris评分术前平均43分(37～62分).结果 23例患者获得随访,随访时间3～47个月,平均26.4个月.术后末次随访时.Harris评分平均83分(67～97分).术中2例发生股骨大转子骨折,无一例发生术后假体周围骨折等并发症.1例术后发生关节脱位,1例发生深静脉血栓,1例术后2周发生急性感染,经扩创、置管冲洗、抗感染治疗成功保留假体;发生异位骨化1例,Brooker Ⅰ级.影像学所有患者股骨柄中置,无内翻或外翻,随访期内无一例发生股骨柄移位(内翻或外翻角度变化>3°).23例患者显示至少Ⅰ区股骨髓内移植骨与周围骨或与股骨柄整合.4例发生股骨柄假体下沉,平均下沉3.3 mm(2～6 mm).结论 股骨侧翻修中,良好的股骨髓内同种异体颗粒骨打压植骨结合合适的非骨水泥延长柄股骨假体,可以修复关节置换术后各种原因所导致股骨骨缺损、重建股骨完整性,具有很好的近期临床疗效.但中远期临床效果尚待进一步观察.     

微创同种异体小颗粒骨植骨治疗骨缺损

目的探索微创同种异体小颗粒冻干骨植骨治疗创伤性骨折伴骨缺损的临床效果。方法采用微创同种异体小颗粒冻干骨植骨治疗创伤性骨折伴骨缺损29例。结果骨折愈合时间(3.10±0.86)个月,术后早期多有中、低度发热,术前与术后化验指标分析显示,CRP、Lg G、Lg M、补体C3、补体C4及嗜酸细胞比值差异有统计学意义(P0.05)。结论微创同种异体小颗粒冻干骨植骨治疗创伤性骨折伴骨缺损,有显著促进骨折愈合的作用,且创伤小、实用性强。     

颗粒骨打压植骨结合非骨水泥臼固定在髋臼翻修中的应用

目的 探讨颗粒骨打压植骨结合非骨水泥臼在髋臼翻修中的临床应用.方法 应用颗粒骨打压植骨结合非骨水泥臼技术重建髋臼骨缺损10例,术中使用异体颗粒骨直径4～6 mm,髋臼假体均为生物型髋臼,上2或3枚螺钉固定,内衬均为高交联聚乙烯.结果 切口均一期愈合,无感染、脱位等并发症发生.随访9～28个月,平均19.5个月,X线片上髋臼骨床、颗粒骨及假体界面未见明显透亮带存在,原骨缺损区修复良好.Harris评分术前平均38.1分,术后平均85.5分.结论 颗粒骨打压植骨结合非骨水泥臼固定方法可有效修复髋关节翻修中髋臼AAOSⅡ、Ⅲ型骨缺损,恢复骨量,并能提供良好的早期稳定性.     

阿仑膦酸钠对人工关节假体周围骨长入的影响

目的观察阿仑膦酸钠对人工关节假体周围骨长入的影响。方法SD雄性大鼠16只,双侧胫骨上端经膝关节植入定制钛合金假体,随机分成对照组和实验组,对照组术后每日空腹生理盐水灌胃;实验组术后每日空腹阿仑膦酸钠灌胃,剂量0.1 mg/(kg.d),持续6周。术后12周处死取材,进行组织学观察及组织形态计量学测定。结果组织学观察发现,对照组假体周围由新生骨、类骨质和纤维界膜构成。纤维界膜较厚,与新生骨或类骨质间界限清晰。实验组假体周围纤维界膜薄且稀少,新生骨与假体界面多为直接接触,有些部位新生骨与假体界面完全整合。组织形态计量学测定发现,对照组假体周围界膜的厚度和面积均明显大于实验组,差异有显著性(P<0.05)。结论阿仑膦酸钠经胃肠给药可能对钛合金人工关节假体周围骨长入有一定的促进作用。     

骨保护素和骨保护素配体在假体周围骨溶解中作用的实验研究

目的通过动物实验模拟聚乙烯颗粒诱导假体周围骨溶解,观察骨溶解的组织学反应和界膜内肿瘤坏死因子-α(TNF-α)、骨保护素(OPG)和骨保护素配体(OPGL)的变化,了解上述物质在磨损颗粒诱导假体周围骨溶解中的作用机理。方法实验选用SPF级雄性SD大鼠24只,经双侧膝关节向股骨远端植入钛合金棒,术后2、4、6、8、10周分别向左侧膝关节注入聚乙烯颗粒,右侧注射生理盐水作为对照,术后12周处死动物取材,观察界膜的组织学改变、TNF-α的浓度和OPG、OPGL的mRNA含量变化。所得数据选用配剥t检验进行统计学分析。结果注射颗粒侧钛合金棒周围有明显界膜形成,界膜中的TNF-α也有明显增高。RT-PCR半定量分析发现,注射颗粒侧界膜组织中OPG mRNA水平低于对照侧,而OPGL mRNA水平则高于对照侧(P＜0．05)。结论聚乙烯颗粒可引起钛合金棒周围多种细胞参与的异物肉芽肿反应,成骨细胞/骨髓基质细胞OPGL的合成增加而OPG的合成减少,此过程可能与TNF-α的升高有关。     

自体骨植骨应用于全髋关节置换术中髋臼缺损疗效分析

目的 探讨自体骨植骨应用于全髋关节置换术(THR)中髋臼缺损的临床疗效.方法 对50例(50髋)髋臼缺损的全髋关节置换术进行分析,根据骨缺损情况进行髋臼自体骨植骨(结构性植骨、颗粒植骨).结果 50例获平均随访24.2个月,49例髋臼植骨处愈合.术后2周Harris评分67～82分,平均79.5分;术后1年86.5～94.6分,平均91.3分.结论 髋臼自体骨植于髋臼骨缺损处,可以恢复髋臼的完整性,增加髋臼的骨覆盖,提高THR术后髋臼假体的稳定性.     

应用解剖型骨水泥股骨假体结合冻干骨打压植骨进行髋关节翻修

[目的]探讨结合应用解剖型骨水泥股骨假体和冷冻干燥颗粒骨打压植骨(IBG)进行股骨翻修的可行性及临床效果。[方法]作者在2001年1月～2005年12月期间,在髋关节翻修中,有49例在股骨翻修中应用解剖型骨水泥柄结合冷冻干燥颗粒骨打压植骨技术,其中有36例(73%)存在严重的骨缺损(Paprosky分型ⅢB或Ⅳ)。平均随访时间为35.3个月(26～52个月)。通过Harris评分和X线片对结果进行评价。[结果]Harris评分从术前的平均44.6分提高到最后评估时的平均88.3分,Harris评分优良率为89.8%。X线片未显示有明显的股骨假体下沉。1例出现术后感染,1例出现术后脱位,感染率及脱位率均为2%,3例出现了术中股骨骨折及股骨柄穿孔,其发生率为6.1%,但这些与假体及植骨材料选择无关。[结论]使用解剖型骨水泥股骨假体结合异体冷冻干燥颗粒骨打压植骨技术,对有严重骨缺损的股骨进行翻修是可行的,并且中短期的临床效果满意,长期效果还有待观察。     

复合骨预制髂骨瓣的实验研究

目的　探讨将一定形状的重组人骨形态发生蛋白 - 2 (rh BMP- 2 )、胶原、珊瑚复合骨植入狗髂骨区 ,预制一定形状和结构的骨组织瓣的可行性。方法　将复合骨植于狗髂骨区 ,同期植入钛种植体 ,3个月、4个半月取材。通过体视学、X线片及组织学等观测指标 ,分析应用 rh BMP- 2、胶原、珊瑚复合骨预制组织瓣的可行性。结果　复合骨植于狗髂骨区 ,3个月时 ,复合骨已转变成骨组织 ,髂骨形状改变 ,并带有种植体 ,种植体与新骨间是骨界面 ;4个半月时新生骨改建为成熟骨。结论　 rh BMP- 2、胶原、珊瑚复合骨适用于体内预制具有一定形状和结构的骨组织瓣。     

骨形态发生蛋白2基因治疗与缓释载体修复骨缺损的比较研究

[目的]比较骨形态发生蛋白2（BMP-2）基因治疗与生长因子缓释方法修复节段性骨缺损效果。[方法]于兔双侧桡骨中段造成1．5cm骨缺损，采用4种方法修复：A组植入转基因骨髓间质干细胞（MSCs）与PLA／PCL（聚乳酸／聚己内酯）支架的复合物；B组植入单纯MSCs与含重组BMP-2的PLA／PCL缓释载体的复合物；C组植入单纯MSCs与PLA／PCL复合物；D组植入单纯PLA／PCL。术后4、8、12周行X线、组织学、生物力学和骨密度等检测，[结果]A组体内植入4周后，成骨细胞和间质细胞呈BMP-2强阳性表达；其成骨速度及成骨质量均明显优于B组，12周时骨缺损完全修复、C组成骨能力较弱，而D组则无新骨形成，残留骨缺损。[结论]BMP-2基因治疗是修复节段性骨缺损的好方法。     

A controlled experimental model of revision implants: Part II. Implementation with loaded titanium implants and bone graft

We used an experimental model producing an aggressive tissue response associated with implant loosening in humans: a 6 mm polymethylmethacrylate (PMMA) cylinder was pistoning 500 microm concentrically in a 7.5 mm hole, with polyethylene (PE) particles, for 8 weeks. At 8 weeks, the PMMA implant was revised with a titanium alloy (Ti) implant, and an identical primary Ti implant was inserted contralaterally for 4 weeks. With this protocol, we evaluated primary and revision plasma-sprayed Ti implants which were loaded under stable conditions with or without allograft, or under unstable conditions without allograft (bilateral primary and revision implants, n 8 per group, 48 implants in 24 dogs). Revision implants had lower interfacial shear strength, less bone in contact with and adjacent to the implant, and resulted in higher levels of IL-6beta and TNFalpha and lower levels of TGFbeta. In both the revision and primary settings, allograft increased shear strength, stiffness and energy, bone-implant contact, and bone area adjacent to the implant. Unstable implants could not generate a mechanically sound interface, and further exacerbated the difference between primary and revision. We conclude that factors important for improving the fixation of revision implants were bone graft and a stable interface.     

A controlled experimental model of revision implants: Part II. Implementation with loaded titanium implants and bone graft

We used an experimental model producing an aggressive tissue response associated with implant loosening in humans: a 6 mm polymethylmethacrylate (PMMA) cylinder was pistoning 500 &#119 m concentrically in a 7.5 mm hole, with polyethylene (PE) particles, for 8 weeks. At 8 weeks, the PMMA implant was revised with a titanium alloy (Ti) implant, and an identical primary Ti implant was inserted contralaterally for 4 weeks. With this protocol, we evaluated primary and revision plasma-sprayed Ti implants which were loaded under stable conditions with or without allograft, or under unstable conditions without allograft (bilateral primary and revision implants, n 8 per group, 48 implants in 24 dogs). Revision implants had lower interfacial shear strength, less bone in contact with and adjacent to the implant, and resulted in higher levels of IL-6 &#103 and TNF &#102 and lower levels of TGF &#103 . In both the revision and primary settings, allograft increased shear strength, stiffness and energy, bone-implant contact, and bone area adjacent to the implant. Unstable implants could not generate a mechanically sound interface, and further exacerbated the difference between primary and revision. We conclude that factors important for improving the fixation of revision implants were bone graft and a stable interface.     

Review article: Treatments for bone loss in revision total knee arthroplasty

Bone deficiency hinders implant alignment and stabilisation of the bone-implant interface in revision total knee arthroplasty (TKA). Treatments for bone defects include bone cement, bone cement with screw reinforcement, metal augments, impaction bone grafts, structural allografts, and tantalum, depending on the location and size of the defects. Small defects are usually treated with cement, cement plus screws, or impaction allograft bone. Large defects are repaired with structural allografts or metal augments. Recent developments involve the use of highly porous osteoconductive tantalum. We reviewed the pros and cons of each method for bone defect management in revision TKA.     

混合植骨技术结合髋臼加强杯或钛网杯重建髋臼严重骨缺损

 目的 探讨自体骨和异体冷冻干燥骨混合植骨方法在治疗髋臼严重骨缺损中恢复髋臼骨量的作用,评价混合植骨技术结合髋臼加强杯或钛网杯重建髋臼的临床效果。方法 1999年4月至2007年12月,采用自体骨和异体冷冻干燥骨混合打压植骨结合髋臼加强杯或钛网杯对髋臼严重骨缺损18例19髋进行重建。男8例,女10例;年龄33~76岁,平均64.7岁。全髋关节置换术后髋臼周围骨溶解导致髋臼假体松动而行翻修术17例,髋臼发育不良行髋臼截骨术后继发髋关节骨关节炎行全髋关节置换1例。Paprosky ⅡB型骨缺损5髋,Paprosky ⅡC型2髋,Paprosky ⅢA型6髋,Paprosky ⅢB型6髋。结果 全部病例随访3.6~12.3年,平均6.5年。Harris髋关节评分由术前平均(38.7±9.6)分提高至末次随访(87.6±7.8)分。术后3~6个月X线检查可见髋臼植骨区骨长入,1年后植骨区骨整合良好。随访期间未发现髋臼再松动病例。1例出现髋臼聚乙烯明显磨损,髋关节旋转中心上移。结论 自体骨和异体冷冻干燥骨混合打压植骨可有效恢复髋臼骨量,植骨中加入的自体骨可促进植骨区骨长入,混合植骨方法结合髋臼加强杯或钛网杯固定治疗髋臼严重骨缺损疗效确切。     

磨损颗粒对滑膜细胞系胞间通讯的影响及其在人工关节无菌性松动 …

目的 通过观察磨损颗粒作用下滑膜细胞系胞间通讯的改变,探讨无菌性松动人工关节假体－骨界面纤维组织异常增生的生物学原因。方法 体外培养获得正常髋关节滑膜细胞系,借助荧光光淬灭恢复技术（ＦＲＡＰ）及激光扫描共聚焦显微镜监测加入１．５ｍｇ／ｍｌ（Ｗ／Ｖ）Ｔｉ合金,ＣｏＣｒ合金或ＵＨＭＷＰＥ颗粒悬液后滑膜细胞间通讯的改变。     

Correlation of Computed Tomography with Histology in the Assessment of Periprosthetic Defect Healing

Computed tomography (CT) may more accurately assess the healing of grafted osteolytic lesions around acetabular components compared with plain radiographs, although clinical validation is lacking. To determine whether clinical or micro-CT imaging could assess accurately the grafted lesion compared with histology, we therefore quantified bone healing and ingrowth to determine an effective rhBMP-2 dose and ratio to allograft bone when grafted adjacent to a cementless porous-coated component. We grafted surgically created acetabular defects in canines (n = 20) before uncemented total hip arthroplasty. At 6 weeks, embedded acetabula were imaged and the CT slice images matched to histology section images. The percentage of bone in the defect and growth into the porous surface was assessed quantitatively. Low-dose rhBMP-2 with allograft (1:5 ratio) resulted in a higher percentage of defect healing (43.8%) than rhBMP-2 alone (29.2%) and a higher percentage of bone ingrowth (15.7%) than allograft bone alone (1.1%) as measured by histology. Micro-CT measurements were similar to histologic measurements of defect healing, whereas clinical CT overestimated periprosthetic bone by 38%. Neither clinical CT nor micro-CT techniques are adequate for assessing ingrowth or the bone-implant interface with metal artifacts.     

Sealing effect of hydroxyapatite coating: a 12-month study in canines

This study addresses the clinical problems regarding access of wear debris to the bone-implant interface and the possible dissemination of polyethylene (PE) particles to distant organs. We inserted two implants into each knee of 7 dogs allowing access of joint fluid to the bone-implant interface with a 0.75 mm initial gap around the implant. Hydroxyapatite (HA)-coated and non-coated (Ti) titanium alloy implants were randomly allocated to each distal femoral condyle. PE particles were repeatedly injected into the right knee joint 3 weeks after surgery for a period of 49 weeks, while only vehicle was injected into the left knee joint. We found huge amounts of PE particles mainly in the bone-implant interface around Ti implants. Infiltration of mononuclear inflammatory cells was present around 3 of 7 Ti implants in relation to PE particles. HA implants had approximately 70% bone ongrowth. In contrast, no bone ongrowth was seen on any Ti implants, all being surrounded by a fibrous membrane. The number of PE particles was evaluated semi-quantitatively. More PE particles were found around Ti implants than with HA implants (p < 0.002). Specimens from iliac lymph nodes, liver, spleen and lung were examined and showed dissemination of PE particles only in regional lymph nodes.     

Sealing effect of hydroxyapatite coating: A 12-month study in canines

This study addresses the clinical problems regarding access of wear debris to the bone-implant interface and the possible dissemination of polyethylene (PE) particles to distant organs. We inserted two implants into each knee of 7 dogs allowing access of joint fluid to the bone-implant interface with a 0.75 mm initial gap around the implant. Hydroxyapatite (HA)-coated and non-coated (Ti) titanium alloy implants were randomly allocated to each distal femoral condyle. PE particles were repeatedly injected into the right knee joint 3 weeks after surgery for a period of 49 weeks, while only vehicle was injected into the left knee joint. We found huge amounts of PE particles mainly in the bone-implant interface around Ti implants. Infiltration of mononuclear inflammatory cells was present around 3 of 7 Ti implants in relation to PE particles. HA implants had approximately 70% bone ongrowth. In contrast, no bone ongrowth was seen on any Ti implants, all being surrounded by a fibrous membrane. The number of PE particles was evaluated semi-quantitatively. More PE particles were found around Ti implants than with HA implants (p < 0.002). Specimens from iliac lymph nodes, liver, spleen and lung were examined and showed dissemination of PE particles only in regional lymph nodes.     

PMMA particles and pressure--a study of the osteolytic properties of two agents proposed to cause prosthetic loosening.

Amongst the wear debris particles implicated in the particle hypothesis for prosthetic loosening are polymethylmethacrylate (PMMA), and particularly PMMA with barium sulphate contrast agent. Another suggested cause for loosening is hydrostatic pressure. PMMA particles were combined with hydrostatic pressure in a study to investigate whether there could be a synergistic or additive effect between these two factors. Titanium plates were fastened onto tibiae of 59 rats. After osseointegration, PMMA particles with barium sulphate were administered to the bone-implant interface. Further, PMMA particles were introduced into a previously published model for hydrostatic pressure induced osteolysis. There was measurable resorption in response to the PMMA particles but no additive or synergistic effect from introducing particles to the pressure model, and the effect of pressure was far greater than that of particles. These results suggest that, whereas particles can be shown to elicit an osteolytic response, the much less studied osteolytic effects of pressure could be far more important.     

The effect of impaction and a bioceramic coating on bone ingrowth in porous titanium particles

Background and purpose Porous titanium (Ti) particles can be impacted like cancellous allograft bone particles, and may therefore be used as bone substitute in impaction grafting. We evaluated the effect of impaction and of a thin silicated biphasic calcium phosphate coating on osteoconduction by Ti particles.

Methods The bone conduction chamber of Aspenberg was used in goats and filled with various groups of coated or uncoated small Ti particles (diameter 1.0–1.4 mm). Impacted allograft bone particles and empty chambers were used in control groups. Fluorochromes were administered at 4, 8, and 12 weeks. Maximum bone ingrowth distance was evaluated by histomorphometric analysis.

Results Histology of Ti particle graft cylinders showed a dense matrix with narrow inter-particle and intra-particle pores (< 100 μm), occluding the lumen of the bone chamber. Bone ingrowth distances gradually increased with time in all groups. Maximum bone ingrowth distance was higher in originally empty chambers than those with allograft bone particles (p = 0.01) and Ti particles (p < 0.001). Maximum bone ingrowth in allograft bone particles was higher than in all Ti groups (p ≤ 0.001). Impaction reduced osteoconduction and the coating partially compensated for the negative effect of impaction, but these differences were not statistically significant. No osteolytic reactions were found.

Interpretation Osteoconduction in the bone conduction chamber was reduced more by the insertion of small Ti particles than by insertion of small allograft bone particles. The osteoconductive potential of porous Ti particles should be studied further with larger-sized particles, which may allow bone ingrowth after impaction through larger inter-particle pores.