同种异体骨软骨移植修复关节软骨缺损研究现状

关节软骨缺损常因软骨再生能力低而难以自行修复.新鲜的同种异体骨软骨移植修复关节软骨缺损的疗效稳定,成功率逐渐提高.冷冻保存的同种异体骨软骨移植修复关节软骨缺损的成功率可与新鲜的同种异体骨软骨移植媲美,梯度降温法是目前保存软骨细胞存活率最好的冷冻方法.该文就同种异体骨软骨移植的实验和临床研究、免疫排斥问题及其相关研究动态作一综述.     

新鲜和深低温冷冻同种异体骨软骨移植长期转归实验研究

[目的]观察和比较新鲜和深低温冷冻同种异体骨软骨移植后的长期转归情况,为同种异体骨软骨移植治疗关节软骨缺损进一步提供理论基础。[方法]建立兔膝关节软骨缺损模型,行新鲜和深低温冷冻同种异体骨软骨移植。在术后12个月和18个月,骨软骨移植物取材进行关节软骨蛋白多糖、软骨细胞活性检测和软骨细胞超微结构观察。[结果]新鲜和冷冻骨软骨移植物中蛋白多糖阿尔新蓝染色强度和存活软骨细胞比率术后均下降,且在各时间点新鲜移植组的结果优于冷冻移植组,有统计学差异(P0.05)。超微结构显示软骨细胞退行性改变。[结论]新鲜和深低温冷冻同种异体骨软骨在移植术后较长时间均出现严重退变,冷冻骨软骨移植物退变较严重,其作为关节软骨缺损治疗方法目前是不可行的。     

关节镜下自体骨软骨移植修复软骨缺损

目的探讨在关节镜监视下,非负重区自体骨软骨移植修复负重区软骨缺损的可行性、效果及并发症。方法2000年8月～2003年8月,对25例软骨缺损患者采用镶嵌式骨软骨移植技术,在关节镜下行相同关节内非负重区自体骨软骨移植修复软骨缺损,作为移植组,定期随访,观察患者症状缓解及软骨愈合情况。同时回顾性分析25例剥脱性骨软骨炎患者,行局部刨削、钻孔减压后症状缓解情况及软骨缺损自行修复情况,作为对照组。两组患者术前Brittberg-Peterson功能评分分别为98.65±9.87、96.98±8.94分。术后1年行膝关节MRI检查评价疗效。结果术后获随访3～24个月。移植组患者膝关节活动良好,疼痛基本消失,术后1年复查MRI示原软骨缺损区软骨表面光滑,移植物位置良好;术后2周Brittberg-Peterson功能评分,其中22例评分为0分,3例因活动后轻微疼痛评分为4分;术后3个月,24例评分为0分,1例评分为3分。对照组术后2周Brittberg-Peterson功能评分为24.63±10.51分,同时诉感觉良好;术后3个月,评分为58.48±6.98分。各组手术前后及组间Brittberg-Peterson功能评分差异均有统计学意义(P<0.01)。结论关节镜下自体骨软骨移植术后效果良好,创伤小,且能避免异体移植产生的排斥反应及疾病传播,是修复软骨缺损的较好方式。但长期疗效仍需进一步探讨。传统的关节内刨削、钻孔减压,对缓解症状也有一定效果。     

同种异体骨软骨移植修复关节软骨缺损的研究进展

同种异体骨软骨移植修复膝关节软骨和骨软骨缺损适用于大面积骨软骨缺损的修复,且不受缺损形状和面积的限制,在临床上已取得令人鼓舞的结果。现对国内外同种异体骨软骨移植修复关节软骨缺损的研究进展作一综述。     

同种异体骨软骨移植修复软骨损伤的研究进展

关节软骨损伤的治疗是骨科领域一个难题,同种异体骨软骨移植是修复全层软骨损伤的有效方法.文中综述了同种异体骨软骨移植修复软骨损伤的研究进展,包括该方法的适应证和禁忌证,目前在临床的应用情况及治疗效果,并进一步探讨了同种异体骨软骨移植中的3个热点话题,如疾病传播、免疫排斥和移植物的保存.这些文献综述显示同种异体骨软骨移植修复关节软骨损伤具有特定优势,但进一步推广该方法仍有一些需要解决的问题.     

关节镜辅助下同种异体骨软骨移植修复膝关节剥脱性骨软骨炎

目的 评价关节镜辅助下采用同种异体骨软骨移植修复膝关节剥脱性骨软骨炎(osteochondritis dis-secans,OCD)伴大面积骨软骨缺损的可行性和有效性.方法 2004年1月-2007年5月,收治13例膝关节股骨髁OCD伴大面积骨软骨缺损患者.男7例,女6例;年龄18～59岁.左膝8例,右膝5例;病程7 d～20年,中位病程为42个月.4例有明确膝关节扭伤史.受累部位:股骨内侧髁外侧份5例,股骨内侧髁滑车面2例,股骨外侧髁6例.主动关节活动度为(95.0±13.5)°.Lysholm膝关节功能评分为(62.23±7.79)分.软骨损伤根据国际软骨修复协会分型和关节镜下的Guh1分型,均为Ⅳ型.关节镜下见骨软骨缺损面积为3～7 cm2,平均4.32 cm2;缺损深度0.8～2.0 cm,平均1.55cm.采用同种异体骨软骨块修复缺损,并联合可吸收钉固定骨软骨块.术后指导功能锻炼.结果 术后伤口均Ⅰ期愈合.13例均获随访,随访时间1年2个月～4年,平均2.2年.术后3个月2例持续活动1 h以上后膝关节疼痛,指导其功能锻炼后缓解.术后6个月2例关节摩擦感明显,关节稳定性尚好,予药物保守治疗.末次随访时主动关节活动度为(137.0±9.8)°,与术前比较差异有统计学意义(P<0.05).X线片检查示术后4～6个月移植骨软骨与受区松质骨融合,关节面平整,关节间隙正常.末次随访EMRI检查示骨软骨愈合,关节面完整;骨软骨移植物无缺损、退行性变.术后1年Lysholm膝关节功能评分为(92.08±7.64)分,与术前比较差异有统计学意义(P<0.05).结论 对于膝关节股骨髁OCD伴大面积骨软骨缺损,在关节镜辅助下采用同种异体骨软骨移植修复缺损能重建关节面的完整性和恢复关节稳定性,可取得良好的治疗效果.     

自体骨软骨移植治疗股骨髁关节软骨缺损

目的探讨关节镜下自体骨软骨移植治疗关节软骨缺损的可行性。方法16例膝关节软骨缺损患者,关节镜下在其非负重区的软骨面上用专用器械凿取圆柱状骨软骨,移植至软骨缺损部位以修复缺损。术后行系统功能锻炼和MRI检查。结果随访7～20个月,患者关节症状消失,关节活动度正常,MRI显示原关节软骨缺损区表面平整,移植骨软骨位置良好。Brittberg-Peterson评分：13例0分,2例2分,1例1分。结论关节镜下自体镶嵌式骨软骨移植术创伤小,操作简单,能保持关节面曲度,可用于修复关节软骨缺损。     

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。     

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。     

同种异体软骨移植修复关节软骨缺损实验研究

目的 采用兔膝关节软骨标本经打孔梯度降温冻存后行同种异体移植,研究打孔梯度降温冻存对兔关节软骨的影响及其修复关节软骨缺损的效果.方法 自16只2月龄新西兰白兔膝关节股骨髌面取分别取3块骨软骨移植物,随机分为3组.Ⅰ组为实验组,在软骨上以3 mm×3 mm矩阵打孔,Ⅱ、Ⅲ组为对照组,不打孔.分别将软骨标本置于二甲基亚砜冷冻保护溶液中,并经梯度降温至-80℃(Ⅰ、Ⅱ组)或直接置于-80℃(Ⅲ组)保存1周,复温后移植到成年兔相应膝关节部位.术后分批处死动物,通过对移植物的大体形态学、组织学、免疫组化染色光镜观察,研究各组移植物保存效果的差异.结果 Ⅰ、Ⅱ组光镜观察结果明显优于Ⅲ组;Ⅰ组与Ⅱ组结果差异不明显,但Ⅰ组对中间层软骨组织的保护明显加强.结论 关节软骨的梯度降温冷冻保存效果明显优于快速降温冷冻保存,且关节软骨打孔冷冻保存对深层软骨细胞有一定的保护作用,可提高软骨细胞存活率,延缓移植软骨组织的退变过程.     

关节镜下行膝关节自体软骨移植术后早期个体化康复训练疗效分析

目的分析关节镜下行膝关节自体软骨移植术后早期个体化康复训练的疗效。 方法选取2016年1月至2017年1月在湖州市第一人民医院接受关节镜下软骨移植修复膝关节软骨缺损治疗的37例患者。其中股骨内髁负重面软骨损伤27例,股骨外髁负重面软骨损伤10例;按照国际软骨修复协会标准分级,软骨缺损深度分别为Ⅱ级3例、Ⅲ级34例;34例软骨损伤面积为1.5～3.0 cm²,3例大于3 cm²。术前通过评估建立功能档案,参与康复学堂,制定个体化康复训练方案。术后按训练方案进行早期功能锻炼。采用Brittberg-Peterson功能评定标准评估患者自体软骨移植前后膝关节功能。采用配对t检验比较患者自体软骨移植前后Brittberg-Peterson功能评分。P<0.05为差异有统计学意义。 结果截至2017年1月,37例患者术后随访12～20个月,均无失访。术后12个月行膝关节MRI检查,示原软骨缺损区软骨表面平整,移植骨软骨柱位置良好。经康复训练后,37例患者膝关节Brittberg-Peterson功能评定标准评分平均为(62.2±1.4)分,低于术前(81.6±1.2)分,差异有统计学意义(t＝63.21,P<0.05);其中关节绞锁、关节肿胀、跑步困难、关节疼痛等13项指标较术前均有明显改善(P均<0.05)。 结论早期个体化康复训练对关节镜下膝关节自体软骨移植术后膝关节功能的恢复有显著作用。     

Osteochondral multiple autograft transfer (OMAT) for the treatment of cartilage defects in the knee joint

The ideal articular cartilage repair tissue should be durable and well-integrated. We have been performing osteochondral multiple autograft transfers (OMAT) since 1996 with the experience we had using carbon fiber implants. We call this technique OMAT instead of mosaicplasty because we use uniform osteochondral autografts. Osteochondral multiple autograft transfer (OMAT) was performed either by arthrotomy or arthroscopy on 12 patients (6 male and 6 female) for the treatment of cartilage defects in the knee joint. The patients ranged in age from 20 to 63 years (mean: 38 years). All had weightbearing-related pain or decrease in the range of motion. None had instability or malalignment. The average follow-up time was 4 years (range: 2 to 8 years). Clinical results were satisfactory. All of the paients were improved initially by the procedure and 85% are still pain free. The mean Lysholm knee rating score was 56 points preoperatively and 86 points postoperatively. Second-look arthroscopy (five patients) demonstrated a normal shiny appearance and color of the grafted area. We observed slight joint effusion postoperatively that disappeared in two months. There was no donor site morbidity. OMAT is a promising surgical technique for the treatment ofarticular cartilage defects. Long-term follow-up with more patients and histological and biomechanical evaluation of chondral interfaces are the subjects of our continuing study.     

髌股关节软骨损伤对Oxford单髁置换术的疗效研究

目的探讨单髁置换术对膝前内侧骨关节炎合并髌股关节软骨损伤患者术后疗效的影响。方法选择自2016年3月至2018年8月期间,山西医科大学附属人民医院骨科关节微创病区完成的单髁置换病例67例,均因为膝前内侧骨关节炎就诊,所有病例均为单侧膝关节置换。其中男19例,女48例;年龄51~84岁,平均(64.67±8.37)岁;左膝41例,右膝26例;身体质量指数(body mass index,BMI)19.56~30.47kg/m 2,平均(25.27±2.56)kg/m 2;病程为0.5~20.0年,平均(5.08±4.83)年。术中通过Outerbridge分级记录观察到的髌股关节软骨损伤并进行分组,术后随访通过牛津膝关节评分(oxford knee score,OKS)、Lonner髌股关节评分评价术后疗效、髌股关节疼痛及功能改善情况,对术前及术后随访的评分分别进行统计学分析,以P<0.05为差异有统计学意义。结果所有患者均完成随访,随访时间12~25个月,平均(18.12±3.68)个月;OKS评分由术前平均(44.42±4.86)分降低至术后平均(21.46±4.64)分(P<0.01);Lonner疼痛评分由术前平均(29.91±2.48)分提高至术后平均(49.54±2.42)分(P<0.01);Lonner功能评分由术前平均(23.17±1.40)分提高至术后平均(38.89±1.41分)(P<0.01)。术中观察发现35膝(52%)合并内侧髌股关节软骨损伤病例,与无髌股关节软骨损伤病例(32膝)相比,术后髌股关节疼痛感及功能均得到改善,术后1、3、6、12个月OKS评分、Lonner疼痛与功能评分对比,差异均无统计学意义(P>0.05)。结论术中证实的内侧髌股关节软骨损伤并不影响Oxford单髁置换术短期疗效。单髁置换术可作为合并内侧髌股关节软骨损伤的膝前内侧骨关节炎患者的治疗方式。     

The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study

BACKGROUND: Microfracture is a frequently used technique for the repair of articular cartilage lesions of the knee. Despite the popularity of the technique, prospective information about the clinical results after microfracture is still limited. The purpose of our study was to identify the factors that affect the clinical outcome from this cartilage repair technique. METHODS: Forty-eight symptomatic patients with isolated full-thickness articular cartilage defects of the femur in a stable knee were treated with the microfracture technique. Prospective evaluation of patient outcome was performed for a minimum follow-up of twenty-four months with a combination of validated outcome scores, subjective clinical rating, and cartilage-sensitive magnetic resonance imaging. RESULTS: At the time of the latest follow-up, knee function was rated good to excellent for thirty-two patients (67%), fair for twelve patients (25%), and poor for four (8%). Significant increases in the activities of daily living scores, International Knee Documentation Committee scores, and the physical component score of the Short Form-36 were demonstrated after microfracture (p < 0.05). A lower body-mass index correlated with higher scores for the activities of daily living and SF-36 physical component, with the worst results for patients with a body-mass index of >30 kg/m(2). Significant improvement in the activities of daily living score was more frequent with a preoperative duration of symptoms of less than twelve months (p < 0.05). Magnetic resonance imaging in twenty-four knees demonstrated good repair-tissue fill in the defect in thirteen patients (54%), moderate fill in seven (29%), and poor fill in four patients (17%). The fill grade correlated with the knee function scores. All knees with good fill demonstrated improved knee function, whereas poor fill grade was associated with limited improvement and decreasing functional scores after twenty-four months. CONCLUSIONS: Microfracture repair of articular cartilage lesions in the knee results in significant functional improvement at a minimum follow-up of two years. The best short-term results are observed with good fill grade, low body-mass index, and a short duration of preoperative symptoms. A high body-mass index adversely affects short-term outcome, and a poor fill grade is associated with limited short-term durability.     

Osteochondral autologous transplantation for the treatment of full-thickness articular cartilage defects of the shoulder

We performed eight osteochondral autologous transplantations from the knee joint to the shoulder. All patients (six men, two women; mean age 43.1 years) were documented prospectively. In each patient the stage of the osteochondral lesion was Outerbridge grade IV with a mean size of the affected area of 150 mm2. All patients were assessed by using the Constant score for the shoulder and the Lysholm score for the knee. Standard radiographs, magnetic resonance imaging and second-look arthroscopy were used to assess the presence of glenohumeral osteoarthritis and the integrity of the grafts. After a mean of 32.6 months (8 to 47), the mean Constant score increased significantly. Magnetic resonance imaging revealed good osseointegration of the osteochondral plugs and congruent articular cartilage at the transplantation site in all but one patient. Second-look arthroscopy performed in two cases revealed a macroscopically good integration of the autograft with an intact articular surface. Osteochondral autologous transplantation in the shoulder appears to offer good clinical results for treating full-thickness osteochondral lesions of the glenohumeral joint. However, our study suggests that the development of osteoarthritis and the progression of pre-existing osteoarthritic changes cannot be altered by this technique.     

Spontaneous repair of full-thickness defects of articular cartilage in a goat model. A preliminary study

BACKGROUND: Full-thickness defects measuring 3 mm in diameter have been commonly used in studies of rabbits to evaluate new procedures designed to improve the quality of articular cartilage repair. These defects initially heal spontaneously. However, little information is available on the characteristics of repair of larger defects. The objective of the present study was to define the characteristics of repair of 6-mm full-thickness osteochondral defects in the adult Spanish goat. METHODS: Full-thickness osteochondral defects measuring 6 x 6 mm were created in the medial femoral condyle of the knee joint of adult female Spanish goats. The untreated defects were allowed to heal spontaneously. The knee joints were removed, and the defects were examined at ten time-intervals, ranging from time zero (immediately after creation of the defect) to one year postoperatively. The defects were examined grossly, microradiographically, histologically, and with magnetic resonance imaging and computed tomography. RESULTS: The 6-mm osteochondral defects did not heal. Moreover, heretofore undescribed progressive, deleterious changes occurred in the osseous walls of the defect and the articular cartilage surrounding the defect. These changes resulted in a progressive increase in the size of the defect, the formation of a large cavitary lesion, and the collapse of both the surrounding subchondral bone and the articular cartilage into the periphery of the defect. Resorption of the osseous walls of the defect was first noted by one week, and it was associated with extensive osteoclastic activity in the trabecular bone of the walls of the defect. Flattening and deformation of the articular cartilage at the edges of the defect was also observed at this time. By twelve weeks, bone resorption had transformed the surgically created defect into a larger cavitary lesion, and the articular cartilage and subchondral bone surrounding the defect had collapsed into the periphery of the defect. By twenty-six weeks, bone resorption had ceased and the osseous walls of the lesion had become sclerotic. The cavitary lesion did not become filled in with fibrocartilage. Instead, a cystic lesion was found in the center of most of the cavitary lesions. Only a thin layer of fibrocartilage was present on the sclerotic osseous walls of the defect. Specimens examined at one year postoperatively showed similar characteristics. CONCLUSIONS: Full-thickness osteochondral defects, measuring 6 mm in both diameter and depth, that are created in the medial femoral condyle of the knee joint of adult Spanish goats do not heal spontaneously. Instead, they undergo progressive changes resulting in resorption of the osseous walls of the defect, the formation of a large cavitary lesion, and the collapse of the surrounding articular cartilage and subchondral bone. CLINICAL RELEVANCE: As surgeons apply new reparative procedures to larger areas of full-thickness articular cartilage loss, we believe that it is important to consider the potential deleterious effects of a "zone of influence" secondary to the creation of a large defect in the subchondral bone. When biologic and synthetic matrices with or without cells or bioactive factors are placed into surgically created osseous defects, the osseous walls serve as shoulders to protect and stabilize the preliminary repair process. It is important to protect the repair process until biologic incorporation occurs and the chondrogenic switch turns the cells on to synthesize an articular-cartilage-like matrix. It takes a varying period of time to fill a large, surgically created bone defect underlying a chondral surface. The repair of such a defect requires bone synthesis and the reestablishment of a subchondral plate with a tidemark transition to the new overlying articular surface. The prevention of secondary changes in the surrounding bone and articular cartilage and the durability of the new reparative tissue making up the articulating surface are issues that must be addressed in future studies.     

Autologous osteochondral grafting in the knee: indication,results, and reflections

The use of multiple autologous osteochondral plugs (mosaicplasty) for repair of articular cartilage defects is a well-accepted technique. Since 1995, the authors have used mosaicplasty to treat more than 110 patients with cartilage defects of the knee, hip, and ankle. The first 52 consecutive patients who had mosaicplasty of the knee and have an average followup of 37 months (range, 24-56 months) were examined. Indications for surgical treatment were osteochondritis dissecans, acute trauma, and posttraumatic lesions of the femorotibial joint, femoropatellar maltracking with recurrent episodes of patella dislocations, and distinct femoropatellar arthrosis. Preoperatively, cartilage defects were classified as International Cartilage Repair Society Grade III lesions in 23 patients and Grade IV lesions in 29 patients. Two years after surgery, an increased level of knee function was found in 86% of the patients. At the latest followup, improved knee function was observed in 92% of the patients. In four patients, reoperation was necessary because of graft failure. Complications and reoperation rate were related to large surface lesions. Autologous osteochondral transplantation is a valid option for the treatment of full-thickness osteochondral defects. However, the method is limited by the defect size and the number of plugs to be taken at the donor site.     

人异体骨软骨移植物保存方法研究

[目的]探讨六种保存方法对人关节软骨组织结构和细胞活性的影响,寻求一种保存效果较好的方法,为临床提供一种有活性的异体骨软骨移植物.[方法]自捐献新鲜尸体膝关节利用专用手术器械获取4.5 mm ×4.5 mm大小的人骨软骨块,分别采用梯度降温法、Co60射线照射+梯度降温法、玻璃化法、连续降温法、直接液氮法和酒精浸泡法对软骨块进行保存处理,分别于保存第8、15、30、60d时,采用蕃红-O组织染色、扫描电镜、软骨细胞胎盼蓝染色、MTT法等,观察并比较以上6种方法保存后关节软骨细胞存活率及其代谢功能变化.[结果]除了酒精保存方法外,其余保存方法随着时间延长软骨组织的细胞成活率和细胞代谢活性逐渐降低;保存60d时,采用玻璃化法保存软骨组织的细胞存活率为62.47％,软骨基质成分丢失较少,胶原纤维断裂不明显;采用慢速梯度降温法保存软骨组织的细胞存活率为59.75％,软骨基质成分丢失较多,胶原纤维断裂明显;其他保存方法软骨细胞存活率不足40％,软骨基质成分大量丢失,胶原纤维杂乱.[结论]六种保存方法中,玻璃化保存法能够较好的保存关节软骨,活性最好,其次是梯度降温保存法,两者均具有一定临床价值.Co60射线照射对软骨细胞有一定的损伤作用;酒精浸泡不能保存软骨细胞活性.