基质诱导自体软骨细胞移植修复膝关节软骨损伤的早期疗效

目的探讨基质诱导自体软骨细胞移植修复膝关节软骨损伤的早期疗效。方法基质诱导自体软骨细胞移植修复50例膝关节软骨损伤患者,全程关注治疗情况。结果患者均获12个月随访。术后6个月36例疾病症状显著改善。术后12个月,膝关节功能主观评分表(IKDC) 2000分值、关节活动度均较术前明显提高(P 0. 01),MRI、关节镜检查显示关节软骨以及软骨下骨修复明显。结论对膝关节软骨损伤患者实施基质诱导自体软骨细胞移植,操作简便,安全且创伤轻。     

自体软骨细胞移植修复关节软骨缺损

关节软骨的自身修复能力有限，其损伤后的修复一直是骨科界的难题之一。1968年，Chestemlan等首次报告了运用体外培养的异体软骨细胞移植修复关节软骨缺损的实验研究，结果虽不理想，但为关节软骨缺损修复开辟了一条新思路。1987年，Brittberg等首次在临床上应用自体软骨细胞联合骨膜移植术治疗膝关节全层软骨缺损。术后经过平均3     

自体骨软骨镶嵌移植术修复关节软骨缺损

目的：回顾性分析关节镜下自体骨软骨镶嵌式移植术治疗负重面关节软骨损伤的可行性。方法：采用Smith Nephew镶嵌式骨软骨移植器，在关节镜下挖取膝关节非负重关节面骨软骨条，并将之移检修复膝关节负重面的局灶性软骨缺损。结果：手术15例，术后随访7—12个月，平均9个月，均达到优良效果。结论：自体关节骨软骨镶嵌移植术对关节负重面局灶性软骨缺损有较好、确实的治疗效果。     

基质诱导的自体软骨细胞移植一例

患者 男 26岁，2004年11月就诊，主诉“外伤后左膝疼痛伴功能障碍5个月余”。患者左膝疼痛，跛行步态，上，下楼加重。查体左膝无红、肿、热，有压痛，     

基质诱导的自体软骨细胞移植术修复膝关节软骨缺损10例术后2年的随访

目的应用基质诱导的自体软骨细胞移植技术(MACI,Genzyme,America)对膝关节软骨损伤的患者进行治疗,通过对患者进行术后2年的随访分析,评价MACI治疗的安全性和有效性。方法从2004年至2008年11月,对10例患者实施MACI手术。患者平均年龄34.9岁(14～57岁),缺损的平均面积(3.69±2.62)cm2/处(0.4～8cm2,n=20)。MACI技术是从患者非负重区取自体关节软骨,进行体外消化并分离出软骨细胞,培养扩增后接种在Ⅰ/Ⅲ型双层胶原膜上。移植前按缺损的部位修剪成相应形状,用生物蛋白胶将胶原膜粘贴在关节软骨缺损处。分别于术前1周、术后3个月、6个月、1年和2年使用KOOS评分问卷进行临床康复效果的评估并进行术后核磁共振的检测(MRI)。此外,术后对2例患者进行了3次关节镜检查和2次组织学检测。结果 10例患者术后均未发生并发症及与手术相关的不良事件。患者术后3个月KOOS评分显示疼痛明显改善(P0.05);术后6个月KOOS评分显示:疼痛、症状、日常生活、运动及娱乐和生活质量5项均明显升高,5项评分间有统计学差异(P0.05)。术后1年和2年患者的情况得到了持续的改善(P0.05)。患者术后3个月的MRI显示软骨缺损部位得到大部分填充和修复;6个月移植软骨基本与周围软骨完全整合;1年后修复组织呈等信号,软骨下骨髓水肿消失;2年后大部分患者软骨修复组织信号与周围组织信号强度一致,软骨下骨无骨髓水肿。术后15个月和2年的组织学检查显示新生的软骨组织以透明软骨为主。MACI手术一般都能在2h内完成,术中出血量小于100ml。结论 MACI技术是修复关节软骨缺损安全、可靠和有效的治疗措施,具有操作简单、手术时间短和术中出血量少等特点。     

自体软骨细胞移植治疗膝关节软骨缺损患者的护理

目的总结纤维蛋白凝胶型自体软骨细胞移植(G-ACI)修复膝关节软骨缺损患者的护理方法。方法 2例膝关节软骨损伤患者,分2次接受手术:第1次均在硬膜外麻醉下行膝关节镜软骨组织取出术,送实验室进行分离培养;1个月后接受第2次手术,分别为纤维蛋白凝胶型自体软骨细胞移植(G-ACI)手术和全镜下G-ACI手术。2例患者术前完善各项评估和检查,做好软骨取出术后护理及自体软骨细胞移植后护理,配合正确而有效的康复训练,并做好并发症预防及护理。结果 2例顺利完成手术,移植术后6周均能扶拐下地,负重1/2体质量,术后10周例1能够完全负重、例2可以3/4负重,术后9个月2例患者均能跑步和骑自行车;移植术后1年可上下楼梯、长途行走,生活质量明显改善。结论术后康复训练是保证自体软骨细胞移植治疗效果的关键因素,给予软骨取出部位及移植后患肢护理,规范的康复训练指导,有利于促进患者康复。自体软骨细胞移植术康复周期长,个体化的、精确的、规范的康复训练计划的实施可有效提高患者治疗效果。     

基质诱导自体软骨细胞移植与软骨缺损的修复

关节软骨缺损的修复,是与皮肤及牙科领域的修复一起问世的,但直到1997年,美国食品药物管理局(FDA)才认可了自体软骨细胞移植治疗软骨缺损的技术(ACI).10多年来,全世界大约已施行了2万多例,但关于其治疗软骨缺损效果的争论仍在继续.面对这些争论,ACI的改进方法--基质诱导自体软骨细胞移植(MACl)出现了.本文就MACI与软骨缺损的修复进行综述.     

自体软骨细胞修复关节软骨缺损的机制探讨

目的:观察团块样自体软骨细胞植入关节软骨缺损后的病理变化,探讨自体软骨细胞移植修复关节软骨缺损的病理生理机制。方法:24只3.0kg以上4～6月龄新西兰大白兔,雌雄不限,随机分为两组:实验组和对照组。实验组12只,20%的速眠新(1mg/kg)肌肉注射麻醉后取肩关节软骨组织,0.2%Ⅱ型胶原酶消化分离软骨细胞,体外单层培养,细胞长成肉眼可见的膜状后收集固体的组织样细胞团,动物再次麻醉制造双膝股骨滑车4.0mm×6.0mm方形缺损,植入细胞团块,骨膜覆盖,缝合骨膜于双股骨髁上。对照组12只,同实验组手术方法进行缺损单纯骨膜移植。1、3、12、24周两组各3只动物空气栓塞处死取材,观察细胞团块变化和缺损修复情况。结果:1周时软骨细胞朝向关节面部分细胞变大变圆,产生大量基质;3周时此种变化更加明显,但骨膜与细胞团块已然不能分开;12周时缺损为类透明软骨组织修复;24周时修复组织为透明软骨样组织,对照组为纤维软骨组织修复。结论:关节软骨细胞体外聚集培养形成的细胞团块内的细胞有迁移生长能力;细胞团块移植方法植入的细胞数量大,表型好,细胞在缺损内不会流失;关节软骨缺损修复是由植入的细胞团块生长分化而来;自体关节软骨细胞团块植入关节缺损内后,在关节应力的影响下,先从朝向关节面的一侧逐渐发生细胞成熟分化和软骨基质产生,逐渐完成缺损的修复。     

自体软骨细胞移植术治疗关节软骨损伤的研究进展

关节软骨再生能力非常有限。目前临床上治疗关节软骨损伤常采用自体软骨细胞移植术(autologous chondrocyte implantation,ACI),其临床效果已得到肯定,但仍不十分理想。随着软骨细胞体外培养、软骨组织工程等相关学科及技术的发展,自体软骨细胞移植术已得到很大改进。然而,要达到理想的透明软骨组织完全修复关节软骨缺损仍有差距。本文从ACI技术的临床效果、软骨细胞体外培养、软骨组织工程、组织学评价和移植后软骨细胞示踪五个方面进行综述。     

自体软骨细胞移植修复猪膝关节软骨缺损的实验研究

目的评价传统和复层高密度培养（复层培养）的自体软骨细胞移植修复关节软骨缺损的效果。方法在8头猪16膝髌切迹上下共建立32个全层软骨缺损，右膝为空白和自体骨膜移植对照组，左膝为传统的自体骨膜覆盖下细胞注射移植组和自体骨膜覆盖下复层培养细胞移植组（上下缺损随机进入各对照和实验组）。术后5-6个月对缺损部位行大体、组织学、免疫组织化学检查。采用O’Driscoll软骨组织形态学评分评价软骨缺损的修复质量。结果四组的O’Driscoll软骨组织形态学评分分别为（3．14±1．95）分、（10．57±3．60）分、（16．29±2．63）分、（20．43±1．81）分，各组之间差异均有统计学意义（P〈0．01）。空白对照组缺损被少量的纤维组织覆盖；骨膜移植组被纤维组织和少量的纤维软骨修复，且与周围组织整合差。自体软骨细胞移植（注射组和复层培养组）缺损被塑形良好的修复组织覆盖，组织学、基质特殊染色示修复组织为纤维软骨和透明软骨，与周边软骨和软骨下骨整合良好。复层培养组修复组织的细胞形态、基质染色比注射细胞组更接近正常软骨。结论自体软骨细胞移植可成功修复全层关节软骨缺损。扩增后的软骨细胞经短期复层培养更有利于软骨缺损的修复。     

细胞载体作为软骨修复中的下一代细胞疗法

背景自从第一位患者接受培养自体软骨细胞移植 （ACI） 以来已过去20多年,新型的软骨修复细胞疗法已经出现.自体培养软骨细胞是第一代细胞疗法,它使用的是混悬培养的自体软骨细胞结合骨膜修补.胶原膜覆盖ACI （CACI）是第二代细胞疗法,它使用的是接种了混悬培养软骨细胞的Ⅰ/Ⅲ型胶原膜上.现今,因关节镜移植术的需求而开发出了第三代细胞疗法,也即采用细胞载体或接种了细胞的支架来移植培养的自体软骨细胞.目的 本文综述了目前基质诱导的自体软骨细胞移植 （MACI） 的情况,它是迄今为止使用最广泛的载体系统.本文还探讨了Ⅰ/Ⅲ型胶原膜的特点、与胶原膜相关的细胞行为、手术技术、康复、临床结果和组织修复效果.研究设计 系统回顾.方法通过搜索 Medline 数据库从1949 年成立以来到 2007年12月的数据,找出相关文献;确认出关于细胞行为、制作过程、手术技术和康复方案的基础和临床研究同行评审的文献.具有原始数据以及使用Ⅰ/Ⅲ型胶原膜的基础和临床研究也被纳入.结果 这些研究获得的数据证实使用MACI治疗的患者在临床结果方面有总体改善.观察到视觉模拟疼痛量表（VAS）评分降低（范围在 1.7～5.32 分）,而改良Cincinnati（范围在3.8～34.2分）评分、Lysholm-Gillquist（范围在23.09～47.6分）评分、Tegner-Lysholm（范围在1.39～3.9分）评分和国际膝关节文献委员会分类量表评分（P〈0.05）均有改善.通过关节镜（包括国际软骨修复学会评分）、MRI 和组织学评估,患者也显示出质量良好的（透明样）组织修复,并且术后并发症发生率较低.结论本综述的结果提示：第三代细胞疗法MACI 程序在治疗有症状的、全层关节软骨缺损修复方面是一种大有前景的方法.     

Autologous implantation of chondrocytes on a solid collagen scaffold: clinical and histological outcomes after two years of follow-up

Abstract From our overall experience in 56 patients, we here report the treatment with matrix-induced autologous chondrocyte implantation (MACI) of 35 patients suffering from knee cartilage defects measuring about 4 cm², and followed for a minimum of 6 months. A total of 36 knees were treated (1 patient on both knees) and clinically observed for 22 months (in some cases for over 39 months), in accordance with a standardised protocol. Subjective parameters (pain, well-being, functional state, symptoms during specific activity) and objective outcomes (IKDC score and Lysholm and Tegner scores) were recorded. One or 2 years after implantation, some biopsies of the regenerated cartilage were histologically evaluated. The subjective parameters (VAS pain score, 2.80±1.49, p<0.0001; change vs. basal score, 2.72) promptly normalized after 1 month, as did the objective ones (IKDC score after 6 months, 1.53±0.59, p<0.0001; change vs. basal score, 1.78). Similar results were observed after the treatment of a femoropatellar kissing lesion. The three cartilage biopsies that were analysed from different patients showed a tissue positivity to immunohistochemical markers of hyaline cartilage. The conclusions of this preliminary analysis are that the clinical outcome and histological evaluation suggest that MACI is able to relieve pain and restore the functionality of the knee, and that the treatment appears capable of regenerating hyaline cartilage.     

低场MRI分级诊断膝关节软骨损伤

目的评价低场MRI分级对诊断膝关节软骨损伤的价值。方法回顾性分析60例(60膝,360处关节面)经关节镜证实的膝关节软骨损伤患者的MRI资料,以关节镜结果为金标准,评价低场MRI分级诊断软骨损伤的价值。结果低场MRI对膝关节软骨损伤的总敏感度、特异度和准确率分别为78.50%(157/200)、91.25%(146/160)和84.17%(303/360);诊断2~4级膝关节软骨损伤与关节镜无差异,对1级诊断有所差异。结论低场MRI对分级诊断膝关节2~4级软骨损伤的价值较高,而对1级损伤价值有限。     

Long-term follow-up evaluation of autologous chondrocyte implantation for symptomatic cartilage lesions of the knee: A single-centre prospective study

IntroductionAutologous Chondrocyte Implantation (ACI) has been the first technique in reconstruction of a valid articular surface. The aim of this study was to evaluate clinical results of this technique at an average follow up of 162 ± 27 months (range 88–208) in a group of patients who underwent ACI.Materials and methods32 patients were operated between 1997 and 2007 for chondral lesions or osteochondritis dissecans of the knee. Mean size of the defect was 5.48 cm² ± 1.53 (range 2–9). Nine patients were treated with I generation technique and 23 with II generation. All patients were evaluated with Subjective IKDC and Tegner Activity Scales for clinical outcomes and with EQ-VAS for a quantitative measure of health after intervention, starting from pre-operative period and at regular follow up (minimum 88 months-maximum 208 months).ResultsA significant increment of all scores was noticed comparing preoperative and postoperative results. In particular medium IKDC score increased from 40.3 ± 9.6 in preoperative evaluation to 74.2 ± 11.6 at one year (p < 0.00001) and to 83.9 ± 10.4 at 5 years follow up (p < 0.001). Mean IKDC values at the last follow-up were 80.3 ± 14.2, showing no statistical differences with those obtained at five-year follow-up. Tegner Activity Scale values increased from 2.8 ± 1.1 preoperatively to 4.1 ± 1.1 (p < 0.0001) after one year and to 6 ± 1.1 at five years (p < 0.0001). Mean Tegner Activity Scale values decreased to 4.8 ± 1.4 at the last follow-up. EQ-VAS evaluation showed superposable results comparing the 5 years evaluation with the ones at a medium follow up of 162 ± 27 months.DiscussionThe most important finding is the reliability at long-term of ACI technique, which in our series gave excellent clinical results. No statistical differences were observed between first- and second-generation. Clinical outcomes were significantly better for defects in the femoral condyles, influenced by age (worse results over 30 years old).ConclusionsACI represents a valid technique for chondral and osteochondral lesions of the knee in a population heterogeneous for age, sex and activity level with good results even at a long term follow up.     

Quantitative analysis of gene expression in human articular chondrocytes assigned for autologous implantation

Autologous chondrocyte implantation (ACI) relies on the implantation of in vitro expanded cells. The aim was to study the dedifferentiation of human articular chondrocytes under different cultivating conditions [days 0–10 in the primary culture (P0); passages in a monolayer from P0 to P3; monolayer vs. alginate and monolayer vs. alginate/agarose hydrogels] using real‐time PCR analysis. The relative gene expressions for collagen type I and II, aggrecan and versican were quantified and the corresponding differentiation indexes (Col2/Col1, Agr/Ver) were calculated. The values of both differentiation indexes decreased exponentially with time in the P0 monolayer culture, and continued with a significant decrease over the subsequent monolayer passages. On the contrary, the chondrocytes seeded in either of the hydrogels significantly increased the indexes compared to their parallel monolayer cultures. These results indicate that alginate and alginate/agarose hydrogels offer an appropriate environment for human articular chondrocytes to redifferentiate after being expanded in vitro. Therefore the three‐dimensional (3D) hydrogel chondrocyte cultures present not only surgical, but also biological advantage over the classic suspension–periosteum chondrocyte implantation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:847–853, 2008     

Third‐generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2‐year randomized trial

Numerous surgical techniques have been developed to treat osteochondral defects of the knee. A study reported encouraging outcomes of third‐generation autologous chondrocyte implantation achieved using the solid agarose‐alginate scaffold Cartipatch®. Whether this scaffold is better than conventional techniques remains unclear. This multicenter randomized controlled trial compared 2‐year functional outcomes (IKDC score) after Cartipatch® versus mosaicplasty in patients with isolated symptomatic femoral chondral defects (ICRS III and IV) measuring 2.5–7.5 cm². In addition, a histological evaluation based on the O'Driscoll score was performed after 2 years. We needed 76 patients to demonstrate an at least 10‐point subjective IKDC score difference with α = 5% and 90% power. During the enrolment period, we were able to include 55 patients, 30 of them were allocated at random to Cartipatch® and 25 to mosaicplasty. After 2 years, eight patients had been lost to follow‐up, six in the Cartipatch® group, and two in the mosaicplasty group. The baseline characteristics of the two groups were not significantly different. The mean IKDC score and score improvement after 2 years were respectively 73.7 ± 20.1 and 31.8 ± 20.8 with Cartipatch® and 81.5 ± 16.4 and 44.4 ± 15.2 with mosaicplasty. The 12.6‐point absolute difference in favor of mosaicplasty is statistically significant. Twelve adverse events were recorded in the Cartipatch® group against six in the mosaicplasty group. After 2 years, functional outcomes were significantly worse after Cartipatch® treatment compared to mosaicplasty for isolated focal osteochondral defects of the femur. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:658–665, 2016.     

Long-term clinical results and MRI changes after autologous chondrocyte implantation in the knee of young and active middle aged patients

Background

Autologous chondrocyte implantation (ACI) represents a valid surgical option for symptomatic full-thickness chondral lesions of the knee. Here we report long-term clinical and MRI results of first-generation ACI.

Materials and methods

Fifteen patients (mean age 21.3 years) underwent first-generation ACI for symptomatic chondral defects of the knee between 1997 and 2001. The mean size of the lesions was 5.08 cm² (range 2–9 cm²). Patients were evaluated using the International Knee Documentation Committee (IKDC) Knee Examination Form, the Tegner Activity Scale, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). High-resolution MRI was used to analyze the repair tissue with nine variables (the MOCART scoring system).

Results

The mean follow-up period was 148 months (range 125–177 months). ACI resulted in substantial improvements in all clinical outcome parameters, even as much as 12 years after implantation. A significant decrease in the MOCART score was recorded at final measurement. Reoperation was required in 2 patients; failure was caused by partial detachment of the graft in both cases.

Conclusion

Autologous chondrocyte implantation is an effective and durable solution for the treatment of large, full-thickness cartilage and osteochondral lesions, even in young and active middle-aged patients. High-resolution MRI is a useful and noninvasive method for evaluating the repaired tissue.

Level of evidence

IV.

     

膝关节软骨人体标本解剖与磁共振成像的比较研究

目的 探讨膝关节尸体标本解剖与磁共振成像(MRI)三维序列-扰相梯度回波序列(3D-FS-SPGR)测量关节软骨厚度的差异,并分析软骨组织主要成分在关节软骨不同位置的差异.方法选用国人青壮年中等身材、无明显关节病变的成年男性尸体膝关节标本2具,首先进行3D-FS-SPGR序列矢状位扫描.复冻后按解剖部位进行矢状位解剖,分别对股骨及胫骨内、外髁负重区前、后面及髌骨面软骨厚度进行测量.关节软骨石蜡切片进行维多利亚蓝-丽春红复合染色并观察.结果 软骨尸体标本解剖与3D-FS-SPGR序列测得的膝关节软骨厚度:股骨外侧髁前负重面平均分别为2.25、2.25 mm,股骨外侧髁后负重面平均分别为2.70、2.75 mm,胫骨外侧髁前负重面平均分别为2.00、2.10 mm;胫骨外侧髁后负重而平均分别为2.35、2.25 mm,股骨内侧髁前负重面平均分别为2.20、2.20 mm,股骨内侧髁后负重面平均分别为2.15、2.30 mm,胫骨内侧髁前负重面半均分别为2.20、2.45mm,胫骨内侧髁后负重面平均分别为2.70、2.95 mm,髌骨面软骨平均分别为3.08、3.15 mm.软骨组织学染色显示:关节软骨表层胶原纤维含量相对较多,软骨细胞及其周围基质相对较少;在关节软骨深层,胶原纤维含量相对较少,而软骨及软骨周围基质相对较多.结论 3D-FS-SPGR序列能够相对真实地反映关节软骨的形态及厚度.胶原纤维主要集中在软骨表层,其分布与软骨的功能相一致.

Abstract：

Objective To compare corpse sampling and MR imaging with 3D-FS-SPGR sequences in measurement of the articular cartilage thickness and to investigate knee cartilage topography. Methods Two fresh specimens of the knee joint were obtained from 2 normal young adult male corpses of medium stature. MR1 scanning was carried on the 2 specimens in sagittal 3D-FS-SPGR MR sequences. After defrosted,the knee specimens were dissected longitudinally, and the cartilage thicknesses were measured at different locations of the knee joint. Paraffin sections of the knee cartilage were observed following compound staining with victoria blue and ponceau red. Results The average cartilage thicknesses measured by dissection and MR imaging sequence were respectively: 2. 25 mm and 2. 25 mm at the anterior weight-loading surface of the femoral lateral condyle, 2. 70 mm and 2. 75 mm at the posterior weight-loading surface of the femoral lateral condyle, 2. 00 mm and 2. 10 mm at the anterior weight-loading surface of the tibial lateral condyle,2. 35 mm and 2. 25 mm at the posterior weight-loading surface of the tibial lateral condyle, 2. 20 mm and 2. 20mm at the anterior weight-loading surface of the femoral medial condyle, 2. 15 mm and 2. 30 mm al the posterior weight-loading surface of the femoral medial condyle, 2. 20 mm and 2.45 mm at the anterior weight-loading surface of the tibial medial condyle, 2. 70 mm and 2. 95 mm at the posterior weight-loading surface of the tibial medial condyle and 3. 08 mm and 3. 15 mm at patella cartilage surface. Collagen fibers were rich at the periphery of the articular cartilage with sparse chondrocytes and matrixes, while the opposite was observed at the center of the articular cartilage. Conclusions MR imaging with 3D-FS-SPGR sequences can display the actual knee cartilage topography. Collagen fibers mainly concentrate at the periphery of the articular cartilage, which accounts for the function of the articular cartilage.