关节镜下应用“微骨折”方法修复关节软骨缺损

目的:探讨关节镜下应用“微骨折”技术对膝关节全层关节软骨缺损修复的效果。方法:对68例全层关节软骨缺损患者进行随机分组:实验组(35例),男17例,女18例,平均年龄35.1岁,采用关节清理后应用“微骨折”技术进行处理,即利用骨刀设计的特性和适度的锤击力量造成软骨下的骨组织微小骨折,刺激软骨生长。对照组(33例),男17例,女16例,平均年龄31.6岁,仅作关节清理术。结果:术后随访6~18个月,平均8.6个月,按Lysholm评分标准,实验组明显优于对照组(P<0.01)。结论:关节镜下应用“微骨折”技术能够显著减轻关节疼痛,增加关节活动度,改善关节功能,是一种简单有效的修复全层关节软骨缺损方法。     

关节镜下“微骨折”技术修复关节软骨缺损的临床研究

目的探讨关节镜下应用＂微骨折＂技术微创修复膝关节全层关节软骨缺损手术的效果。方法全层关节软骨缺损病例进行随机分组,一组作关节清理后应用＂微骨折＂技术进行修复（实验组）,另一组仅作关节清理（对照组）。结果本组68例均获随访,随访时间6～18个月,平均8.6个月。按Lysholm评分标准,对评分结果进行比较分析。术后近期随访,Lysholm评分实验组明显优于对照组。结论关节镜下应用＂微骨折＂技术修复全层关节软骨缺损,经近期随访,膝关节功能恢复较为满意。     

应用微骨折技术修复全层关节软骨缺损

关节软骨对关节功能及骨骺生长非常重要，关节软骨损伤临床并不少见，而软骨本身几乎没有自我修复能力，常常导致关节功能障碍。本实验旨在建立兔股骨内髁全层关节软骨缺损实验模型，利用微骨折技术修复软骨缺损。     

组织工程化软骨修复兔膝关节软骨缺损的实验研究

目的 评估同种异体组织工程软骨修复兔膝关节全层软骨缺损的有效性。方法分离收集成年新西兰大白兔软骨细胞进行体外培养。建立双侧兔膝关节软骨缺损模型，用去端肽胶原（atelocollagen）凝胶与所培养的异体兔关节软骨细胞共同植入兔膝关节软骨缺损处，并设对照组。分别于手术后4周、8周观察大体标本以及组织学修复结果，并进行Wakitan的评分，评估此方法的有效性。结果大体观察结果表明，与对照组相比，实验组缺损处由软骨组织修复而对照组缺损处由纤维样组织填充。组织学观察可以见到实验组关节软骨缺损处有密集的软骨细胞而对照组关节缺损处只有纤维细胞无软骨细胞。结论通过短期观察表明以同种异体软骨细胞-去端肽胶原复合物修复全层软骨缺损的方法是有效可行的，为其进一步临床应用提供了参考。     

应用自体脂肪干细胞修复猪关节软骨缺损的初步实验研究

目的 探索自体脂肪干细胞修复猪关节软骨缺损的可行性.方法 从猪背部脂肪组织中获取脂肪干细胞,经过体外培养扩增,以50×106/ml的浓度将脂肪干细胞接种于PLGA(polylacticacid/polyglycolicacid,PLA/PGA,PLGA)中,细胞材料复合物在体外成软骨诱导2周.于猪膝关节软骨非负重区形成2个直径8mm的环形、全层软骨缺损,实验组回植经诱导后的细胞材料复合物,对照组放置单纯支架材料.术后12周取材,缺损修复区行大体观察、组织学HE及藏红花染色、免疫组化检测.结果 术后12周实验组缺损区大部分被修复,缺损被软骨组织填充,修复区表面光滑.组织学染色显示有典型的透明软骨样结构.藏红花染色发现修复组织表达丰富的聚合蛋白多糖.对照组则未能修复关节软骨缺损,缺损区面积增大,表面覆盖薄层纤维组织.结论 猪自体脂肪干细胞可以作为组织工程种子细胞,修复猪关节软骨缺损.     

微骨折技术结合自体骨软骨碎屑样移植修复兔膝关节软骨缺损的实验研究

目的 评价应用微骨折技术结合自体骨软骨碎屑样团块移植修复兔膝关节软骨缺损的效果. 方法 取健康成年新西兰大白兔46只,随机分为3组:对照组10只,微骨折组18只,实验组18只.制作膝关节软骨缺损模型,对照组不做其他任何处理;微骨折组利用微骨折技术制作网格状微孔;实验组在制作网格状微孔后在缺损表面填盖上碎屑样软骨团块.术后4、8、12周行大体观察、组织学观察及Wakitani组织学评分、糖胺聚糖(GAG)含量测定 结果 术后12周实验组缺损由透明软骨样组织填充,软骨及软骨下骨组织基本恢复,修复的软骨组织在大体观察、组织形态学方面均优于微骨折组和对照组.术后4、8、12周实验组Wakitani组织学评分平均分别为(5.0±1.0)、(6.7±1.5)、(13.0±1.0)分,微骨折组平均分别为(2.3±0.6)、(5.0±1.0)、(7.7±1.2)分,对照组平均分别为(0.0±0.0)、(1.3±0.6)、(1 7±0.6)分,实验组不同时间点评分均高于微骨折组和对照组,差异有统计学意义(P＜0.05).术后4、8、12周实验组GAG含量平均分别为(6.25±0.31)、(13.11±0.21)、(16.23±0 66) μg/mg,微骨折组平均分别为(3.04±0.21)、(5.75±0.24) 、(7.03±0.21) μg/mg,两组比较差异均有统计学意义(P ＜0.05). 结论 微骨折技术结合自体骨软骨碎屑样移植是一种治疗软骨缺损的新选择,其能够有效提高软骨修复的效果.     

自体骨软骨移植与含富集骨髓干细胞松质骨移植修复兔关节软骨缺损

目的:评价自体骨软骨移植与含富集骨髓干细胞松质骨镶嵌移植两种方法修复全层关节软骨缺损的生物学特征和效果。方法:采用新西兰大白兔制作左右后肢全层软骨缺损模型,分别进行自体骨软骨镶嵌移植、含富集骨髓干细胞松质骨镶嵌移植修复,对照组不作任何修复,每组12只。术后第4、8、12周处死动物取材,分别进行膝关节活动度测定、大体观察、光镜观察与电镜观察。结果:移植实验组在第12周时均能以类透明软骨组织修复缺损,对照组为纤维肉芽组织。形态学检查表明,两种方法均能以类透明软骨组织覆盖缺损,骨软骨移植组无明显免疫排斥现象,随着时间延长,修复高度逐渐增加。骨软骨移植组同含富集骨髓干细胞松质骨镶嵌移植组效果无显著差别。结论:骨软骨移植、含富集骨髓干细胞松质骨镶嵌移植两种方法均能以类透明软骨组织修复全层关节软骨缺损,含富集骨髓干细胞松质骨镶嵌移植更适用于较大面积软骨缺损的修复。     

兔自体松质骨颗粒修复关节软骨损伤

目的研究兔自体松质骨颗粒在膝关节软骨损伤处移植后能够诱导软骨组织生成、促进关节软骨损伤修复的现象。方法 12只新西兰大白兔麻醉后在兔的右侧膝关节股骨远端内、外侧髁负重区用电钻分别造成直径、深度均为3 mm的骨软骨缺损创面,取同侧髂骨松质骨,制成直径约为1 mm松质骨颗粒植入股骨内侧髁软骨缺损处,作为实验组,外侧髁软骨缺损不做处理作为对照组。术后12周进行膝关节大体观察、病理切片染色,评估关节软骨损伤的修复情况。结果兔膝关节实验组软骨缺损处被新生软骨填充,软骨面光滑,组织切片染色显示有关节软骨形成。对照组缺损创面仍然凹陷,仅在缺损边缘有少量软骨生长。结论兔自体松质骨颗粒在膝关节软骨损伤处能够诱导软骨生成,促进关节软骨的修复,是一种良好的关节软骨损伤修复方法。     

关节软骨缺损修复方法及疗效

关节软骨缺损后自我修复能力很差,治疗方法如关节灌洗清理术、Pridie钻孔术、微骨折术、骨膜和软骨膜移植、骨软骨移植、细胞移植和组织工程化软骨修复等的疗效不一.骨软骨移植和细胞移植技术相对成熟且临床效果较好.组织工程化软骨修复是目前研究的热点且已逐步试用于临床,多重复合的仿生支架和携带细胞因子仍是研究重点,临床实际应用还有待观察.     

间充质干细胞在关节软骨缺损修复中的应用

外伤或炎症造成的关节软骨缺损在骨科临床十分常见。关节软骨缺损可造成疼痛、关节畸形，甚至严重的功能障碍，严重影响人们的生活质量。传统的软骨修复方法包括软骨下钻孔术、磨削术和微骨折术等，临床疗效欠佳。近年来，越来越多的新方法开始应用于关节软骨缺损的基础与临床研究。其中软骨组织工程作为研究的焦点，正日益受到科研工作者和临床医生的广泛关注。     

Intra‐articular injection of rhFGF‐18 improves the healing in microfracture treated chondral defects in an ovine model

Microfracture is a common cartilage repair procedure. Strategies to improve healing post‐microfracture include the use of growth factors to enhance hyaline cartilage production. This study investigates the effect of intra‐articular recombinant human fibroblastic growth factor 18 (rhFHF18) on the healing of a chondral defect treated with microfracture in an ovine model. Chondral defects (8 mm diameter) were created in the medial femoral condyle of 80 sheep (n = 16/treatment group). Defects were treated with microfracture alone or microfracture + intra‐articular rhFGF‐18 (administered either as one or two cycles of 3× weekly injections). Outcome measures included mechanical testing, macroscopic International Cartilage Repair Society repair score, modified O'Driscoll histology score, qualitative histology, and immunohistochemistry for types I, II, and VI collagen. In treated animals, there was a statistically significant improvement in ICRS tissue repair score and tissue infill score, in the modified O'Driscoll score between control and 1 cycle of rhFGF‐18 at 6 m, and in the cartilage repair score and structural characteristic score between the control and both rhFGF‐18 groups at 6 m. There was no evidence of degeneration of adjacent cartilage in the rhFGF‐18 treated cartilage. The increase in hyaline cartilage‐like tissue formed in the microfracture + rhFGF‐18 treated groups indicates that rhFGF‐18 potentiates the formation of hyaline cartilage repair following microfracture. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:669–676, 2014.     

关节镜下微骨折术修复膝关节软骨缺损

目的探讨关节镜下微骨折术修复膝关节软骨缺损的临床效果。方法选取本院2010年10月至2012年10月收治的膝关节软骨缺损患者68例,根据术式分为两组,34例患者在关节镜下采用关节清理术治疗为对照组,34例患者在关节镜下采用微骨折术治疗为观察组,术后随访6个月。两组患者治疗前后均行Tegner运动能力评分和美国特种外科医院（the hospital special surgery,HSS）膝关节功能评分,分析两组患者的临床症状改善情况、手术治疗的临床效果及术后并发症情况。结果治疗后,两组患者Tegner运动能力评分、HSS膝关节功能评分均显著升高。观察组患者Tegner运动能力评分（4.3±1.2）分,HSS膝关节功能评分（84.3±15.2）分,均明显高于对照组（2.7±0.8）分、（61.5±14.8）分,观察组患者术后疼痛病症消失情况（97.1%）,肿胀病症消失情况（100.0%）均明显好于对照组（76.5%）,（82.4%）,观察组患者手术治疗的总有效率（94.1%）明显高于对照组（73.5%）,差异均有统计学意义（P〈0.05）。观察组患者的术后并发症发生率（0）低于对照组（5.9%）,差异无统计学意义（P〉0.05）。结论关节镜下微骨折术是修复膝关节软骨缺损的有效方法,可明显改善患者的临床症状,改善膝关节功能和活动能力,提高治愈率,安全性高。     

新鲜同种异体骨软骨移植修复软骨缺损

目的联合应用新鲜同种异体骨软骨移植,和局部注射碱性成纤维细胞生长因子(basic fibroblast growthfactor,bFGF),探讨能否促进关节软骨缺损区新生软骨的形成,提高软骨缺损修复的成功率。方法48只青紫兰兔,96个实验关节,随机分为A、B、C、D组。无菌条件下制作骨软骨缺损模型。在A组缺损区单纯植入新鲜的同种异体骨软骨,B组单纯局部注射重组人bFGF,C组局部注射bFGF后同时植入新鲜的同种异体骨软骨,D组用作空白对照。术后第4、8、12周作大体观察、X线摄片、组织学检查及免疫组化检查。结果移植加注射bFGF组促进软骨缺损修复的效果均好于其他组,图像分析仪进行软骨细胞记数有显著差异(P<0.05),有统计学意义。修复软骨型胶原免疫组化染色强阳性。结论采用新鲜的同种异体骨软骨移植及联合应用碱性成纤维细胞生长因子,二者能起交互作用,促进了新生软骨的形成。     

孔数不同的骨钻孔术对兔软骨缺损远期修复效果的实验比较

目的: 评价孔数不同的钻孔术对软骨缺损的远期修复效果。方法: 用中国白兔40只, 在股骨髁关节面制造6mm×8mm全层软骨缺损, 分别施行10孔及5孔钻孔术, 孔径1mm, 于术后13个月取材做组织学及电镜观察,并进行评估。结果: (1) 10孔、5孔和对照组中, 优势修复组织为透明软骨者分别占75%、70%、0%。(2) 修复组织厚度: 10孔与5孔无显著性差异, 已接近毗邻软骨厚度。(3) 修复组织覆盖缺损的面积: 10孔>5孔>对照组。结论: 软骨下骨钻孔对关节软骨缺损的远期修复效果良好, 能长期适应关节的运动和负重, 10孔比5孔的修复效果好。     

Formation of cartilage repair tissue in articular cartilage defects pretreated with microfracture and covered with cell‐free polymer‐based implants

The aim of our study was to evaluate the mid‐term outcome of a cell‐free polymer‐based cartilage repair approach in a sheep cartilage defect model in comparison to microfracture treatment. Cell‐free, freeze‐dried implants (chondrotissue®) made of a poly‐glycolic acid (PGA) scaffold and hyaluronan were immersed in autologous serum and used for covering microfractured full‐thickness articular cartilage defects of the sheep (n = 4). Defects treated with microfracture only served as controls (n = 4). Six months after implantation, cartilage implants and controls were analyzed by immunohistochemical staining of type II collagen, histological staining of proteoglycans, and histological scoring. Histological analysis showed the formation of a cartilaginous repair tissue rich in proteoglycans. Histological scoring documented significant improvement of repair tissue formation when the defects were covered with the cell‐free implant, compared to controls treated with microfracture. Immunohistochemistry showed that the cell‐free implant induced cartilaginous repair tissue and type II collagen. Controls treated with microfracture showed marginal formation of a mixed‐type repair tissue consisting of cartilaginous tissue and fibro‐cartilage. Covering of microfractured defects with the cell‐free polymer‐based cartilage implant is suggested to be a promising treatment option for cartilage defects and improves the regeneration of articular cartilage. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1353–1360, 2009     

The effect of hyaluronan combined with microfracture on the treatment of chondral defects: an experimental study in a rabbit model

Because articular hyaline cartilage has low potential for regeneration, numerous methods and techniques have been proposed to induce the reparation process. Microfracture is a convenient procedure for this purpose. However, the quality of the new cartilage after microfracture is still not as proper as original. In this experimental study, we used microfracture in combination with intraarticular application of hyaluronan in rabbit knee articular defect. Bilateral knee arthrotomies, chondral defects, and microfracture were created on each intercondylar notch in thirty rabbits. Rabbits received intraarticular injections of hyaluronan once a week for 3 weeks in the right knee, started from 1 week after injury. The left knees, which served as controls, were injected with normal saline. Biopsy was taken from both knees at the 4th and 6th weeks. In comparison with the control group, after 6 weeks we observed a higher potential for healing in the experimental group, with thicker and more organized repair tissue filling the defect. The current study reveals that application of hyaluronan after the microfracture might be beneficial in inducing articular cartilage defect reparation.     

"双相"组织工程软骨修复兔关节骨软骨缺损

目的探讨“双相”异体骨基质明胶（bonematrixgelatin,BMG）作为组织工程软骨载体,与同体骨髓间充质干细胞（marrowmesenchymalstemcells,MSCs）结合,构建组织工程软骨修复兔关节骨软骨缺损的效果。方法4月龄新西兰兔32只,雌雄不限,体重2～3kg。①体外实验：取5只新西兰兔,处死后取髂骨和四肢骨,制备一侧松质骨,一侧皮质骨的“双相”异体BMG载体,扫描电镜观察。另取新西兰兔18只,抽取骨髓,分离MSCs并诱导成软骨分化;将诱导而来的软骨前体细胞与“双相”BMG载体复合构建组织工程软骨,分别于1、3和5周取材行Masson、PAS染色和扫描电镜观察。②体内实验：将抽取骨髓的18只及余下的9只新西兰兔制成双侧股骨内髁骨软骨缺损模型,将前期制备的组织工程软骨同体植入18只兔的右股骨内髁骨软骨缺损（A组）,左侧缺损移植异体BMG（B组）,其余9只双侧软骨缺损未予处理作为空白对照（C组）,分别于术后1、3和6个月取材,行大体、组织学和Ⅱ型胶原mRNA原位杂交观察,改良Wakitani法评分,比较各组修复效果差异。结果①体外实验：“双相”BMG松质骨面孔隙大小100-800μm,细胞于其中增生,形成富含细胞的软骨层;皮质骨面孔隙大小10～40pm,细胞层状覆盖于其表面,可作为起支撑作用的软骨下骨。②体内实验：A组术后1个月即可重建关节骨软骨缺损;修复软骨在观察期内逐渐变薄,但在6个月内始终保持关节面及软骨下骨结构完整。B、C组未能修复缺损,缺损周边软骨磨损加剧。改良Wakitani评分显示A组在3个时间点的各项评分结果,除6个月软骨厚度外,其它指标均优于B、C组,且差异有统计学意义（P〈0．01）。Ⅱ型胶原mRNA原位杂交显示,A组缺损区修复组织中细胞阳性染色率明显高于B、C组,且差异有统计学意义（P〈0．01）。结论“双相”异体BMG可作为组织工程软骨载体材料,其结合自体MSCs诱导的软骨前体细胞制备的组织工程软骨,可修复兔关节软骨和软骨下骨。     

One-step articular cartilage repair: combination of in situ bone marrow stem cells with cell-free poly(L-lactic-co-glycolic acid) scaffold in a rabbit model

Focal full-thickness articular cartilage defects are challenging to repair. The purpose of this study was to find a simple, effective 1-step articular cartilage repair method. Because stem cell niches produce a microenvironment for stem cell self-renewal, proliferation, and differentiation, we integrated in situ bone marrow stem cells with an implanted poly(L-lactic-co-glycolic acid) (PLLGA) scaffold. Marrow stem cells grew and proliferated on cell-free PLLGA scaffolds, which were evaluated by scanning electronic microscopy (SEM) and Cell Counting Kit-8 (Dojindo, Kumamoto, Japan). Twenty-seven rabbits (54 knees) with large cylinder femoral trochlear cartilage defects were created and repaired with microfracture and cell-free PLLGA scaffold implantation (group 1), microfracture (group 2), or cell-free PLLGA scaffold implantation (group 3).Outcomes were evaluated by magnetic resonance imaging, International Cartilage Repair Society scores, histology, and immunohistochemistry. The repair effects were better in group 1 than in groups 2 and 3. In group 1, hyaline-like cartilage formed at week 24. Magnetic resonance imaging showed homogeneous signals as the adjacent normal cartilage. Collagen type II and toluidine blue were stained positively as normal cartilage tissue, and the color and thickness of regenerated tissue were similar to surrounding normal tissue. The combination of microfracture and cell-free PLLGA scaffold implantation used endogenous marrow stem cells in situ and promoted hyaline-like cartilage regeneration rapidly and effectively.     

异体软骨细胞复合Pluronic修复关节软骨缺损

目的 探讨运用同种异体软骨细胞复合Pluronic修复关节软骨缺损的可行性，并应用^3H—TdR放射自显影方法鉴别软骨缺损修复的细胞来源。方法 取同种异体软骨细胞体外培养至第2代，用^3H—TdR标记后复合Pluronic植入兔关节软骨缺损区作为实验组，并采用单纯Pluronic植入作为材料对照组，不作任何处理组为空白对照组，分别于4、8及16周取材，观察其修复效果，并应用放射自显影方法鉴别修复组织的细胞来源。结果 实验组术后8周，缺损表面可见新生软骨形成，术后16周缺损完全修复，表面光滑，与周围界限模糊，放射自显影证实所修复组织的细胞来源于植入细胞。材料对照组及空白对照组缺损均未见明显修复。结论 ①同种异体软骨细胞复合Pluronic修复关节软骨缺损是可行的；②^3H—TdR标记细胞可作为鉴别细胞来源的一种简便可行的方法。     

应用骨形态发生蛋白(BMP)修复关节软骨缺损的实验研究

目的探讨关节软骨全层缺损应用骨形态发生蛋白修复的效果。方法于2004年5月至2005年12月,30只新西兰种成年兔随机分为A,B,C三组,每只兔子左膝股骨髁间凹做一大小为4mm×5mm×2.5mm的全层关节软骨缺损。A,B组缺损内分别填充骨形态发生蛋白/纤维蛋白胶(BMP/FG)及FG,C组为空白。术后28周对缺损修复情况行大体形态、组织学和电镜观察。结果BMP/FG组,缺损组织以透明软骨修复,接近正常组织,而FG组和空白组则以纤维组织修复为主。结论BMP/FG能较好的完成关节骨软骨全层缺损的修复,并随着时间的延长修复的软骨越接近正常软骨,但修复软骨缺损的组织与邻近正常软骨组织连接性仍不是十分理想。