关节软骨损伤和缺损修复策略

关节软骨的损伤是临床中常见的疾病。由于关节软骨自身修复能力有限,采用关节镜下清创术、软骨移植、软骨细胞移植、组织工程技术及凝胶类关节软骨修复材料是目前对关节软骨损伤进行修复的主要手段。本文对目前用于关节软骨损伤和缺损修复的主要策略及各类修复技术的优缺点进行了综合评述。关节镜下清创术对早期骨性关节炎疗效显著;软骨及软骨细胞移植对小面积软骨缺损修复效果较为理想;组织工程技术是目前对关节软骨损伤和缺损修复的一个热点方向,但存在支架材料与软骨缺损区整合不紧密等问题;凝胶类关节软骨修复材料具有与自然关节软骨相似的力学和生物摩擦学特性,但其生物活性及与自然关节软骨间的结合强度有待进一步提高,如何实现材料生物活性、生物力学性能和生物摩擦学性能功能一体化是凝胶类关节软骨修复材料亟待解决的焦点问题。     

关节软骨组织工程研究进展

组织工程技术为损伤关节软骨的修复提供了全新的治疗方法。本文就关节软骨组织工程的种子细胞、生长因子、细胞外基质支架及修复关节软骨缺损的研究进展作一综述。     

支架及无支架条件下构建组织工程软骨的研究进展

支架材料的研究是组织工程的研究热点之一,软骨细胞复合培养给组织工程软骨的构建带来希望,单一的材料诸如胶原、透明质酸、壳聚糖、纤维蛋白凝胶等已经证明可以与软骨细胞复合培养,两种或者多种材料复合可以提高材料的性能,更好地用于组织工程软骨的构建,并满足软骨缺损修复的需要;同样,在无支架情况下应用软骨细胞聚集培养、沉淀培养的方法,可以构建组织工程软骨,并给软骨缺损的修复带来新希望,但目前的研究较少。两者是组织工程软骨构建的两个主要方向。     

软骨组织工程与细胞黏附关系研究进展

关节软骨是一种无血管组织，损伤后自身愈合能力非常有限，关节软骨缺损的治疗已成为困扰临床医生的一个难题。随着生命科学和工程学的发展，使用组织工程技术构建关节软骨的替代品修复关节软骨损伤已经成为研究热点，目前在临床应用亦已获得成功。组织工程细胞．支架材料之间的紧密黏附反应对细胞的增值、表型的表达、细胞外基质的合成具有重要的作用，但由于种子细胞和载体支架之间的黏附力不强，种子细胞容易从支架上脱落，[第一段]     

水凝胶在软骨组织工程中的应用

成熟的关节软骨无血液供应、神经支配及淋巴同流,故软骨的自身修复能力非常有限.全厚软骨损伤在某些情况下可发牛自发性修复反应,但新形成的组织是纤维性软骨组织,不具有天然透明软骨的生物化学和生物力学特征,通常会在生理负荷下发生退变[1].组织工程的提出及应用为关节软骨缺损的再生修复带来了希望.水凝胶是一种以水为分散介质的高分子网络体系,性质柔软,能保持一定的形状和吸收大量的水.凡是水溶性或亲水性的高分子,通过一定的化学交联或物理交联,都可以形成水凝胶.水凝胶应用丁软骨组织工程,克服了以往支架材料的许多缺陷,本文就水凝胶的部分基础研究及其在软骨组织工程中的应用做一综述.     

水凝胶在软骨组织工程中的应用

成熟的关节软骨无血液供应、神经支配及淋巴同流,故软骨的自身修复能力非常有限.全厚软骨损伤在某些情况下可发牛自发性修复反应,但新形成的组织是纤维性软骨组织,不具有天然透明软骨的生物化学和生物力学特征,通常会在生理负荷下发生退变[1].组织工程的提出及应用为关节软骨缺损的再生修复带来了希望.水凝胶是一种以水为分散介质的高分子网络体系,性质柔软,能保持一定的形状和吸收大量的水.凡是水溶性或亲水性的高分子,通过一定的化学交联或物理交联,都可以形成水凝胶.水凝胶应用丁软骨组织工程,克服了以往支架材料的许多缺陷,本文就水凝胶的部分基础研究及其在软骨组织工程中的应用做一综述.     

组织工程软骨修复关节软骨损伤研究新进展

目前关节软骨损伤修复仍未得到很好的解决,临床修复方法大多近期效果理想,远期效果不确切或者有恶化的倾向[1].随着近几年组织工程技术快速发展,制备具有成软骨活性的人工软骨使之植入人体后能够形成新的软骨组织从而达到软骨修复与重建,为临床治疗软骨损伤带来突破性进展.组织工程软骨应用工程学和生命科学原理将经体外分离、培养的高浓度的种子细胞种植于天然的或人工合成的具有良好生物兼容性和可降解性的聚合物支架,使之植入人体后能够形成新的软骨组织从而达到软骨修复与重建的目的.软骨组织工程研究涉及到种子细胞、支架材料和生长因子3个基本要素.     

关节软骨缺损修复与组织工程

关节软骨缺损自身修复能力很有限,目前的临床治疗手段无法达到满意修复.组织工程的发展为解决这个问题提供了新思路,使软骨组织缺损的完全再生成为可能.组织工程方法修复关节软骨缺损的最终目的是恢复软骨组织结构的完整性和功能稳定性.在细胞选择方面,软骨细胞主要要解决去分化问题,而间充质干细胞因为自体来源、易扩增、具有软骨细胞分化潜能,受到广泛重视,胚胎干细胞主要用于细胞的分化机制研究.生长因子因为作用效果不同,也趋向于联合应用.在支架材料选择方面,复合支架成为研究的主要方向.应用组织工程方法修复关节软骨缺损的效果存在一定的争议,主要是远期功能观察距离临床应用存在一定差距,在修复组织固位和生物力学影响方面还需要进一步研究.     

利用脂肪干细胞构建组织工程软骨修复兔膝关节软骨缺损

目的探讨以脂肪于细胞（ADSCs）复合脱细胞软骨基质支架构建组织工程软骨修复兔膝关节软骨缺损的效果。方法以人关节软骨脱细胞基质为支架，复合经诱导的兔ADSCs，体外分别经静态培养和生物反应器培养，构建组织工程软骨。对膝全厚关节缺损进行修复，并与单支架组、空白对照组比较，其中空白对照组12个关节，脱细胞软骨支架组16个关节，静态培养细胞支架组24个关节，生物反应器培养细胞支架组8个关节。分别于术后3、6个月对修复关节进行大体、组织学及免疫组化观察。结果实际完成观察的关节数为44个，其中空白对照组9个，脱细胞软骨支架组11个，静态培养细胞支架组18个，生物反应器培养细胞支架组6个。空白对照组全为纤维组织或纤维软骨样修复；单支架组5个关节为未成熟透明软骨，无成熟透明软骨形成；静态培养细胞支架组83．3％为透明软骨，其中3个关节为成熟透明软骨，12个关节为未成熟透明软骨；生物反应器培养细胞支架组100％为透明软骨，其中2个为成熟透明软骨，4个为未成熟透明软骨。Wakitani评分各组差异有统计学意义（P〈0．05）。结论ADSCs复合脱细胞软骨基质支架能良好地修复兔膝关节全厚软骨缺损，应用生物反应器技术有助于构建组织工程软骨，促进软骨缺损的修复。     

天然来源可注射水凝胶修复软骨缺损的研究进展

组织工程在软骨缺损修复中发挥重要作用,细胞、支架和生长因子是其3个基本要素。可注射水凝胶修复软骨缺损的优势在于,其交联前形状不固定,可填充不规则缺损,随后通过物理或化学交联使其凝固成固态水凝胶,以使缺损填充"严丝合缝"。天然材料凭借其类似于细胞外基质成分、可模拟机体组织微环境及有利于维持软骨细胞表型等特性成为软骨缺损修复支架的主流材料。该文就天然来源可注射水凝胶的研究进展作一综述。     

Articular cartilage. Anatomy, injury, and repair

Articular cartilage plays a vital role in joint morphology. An understanding of articular cartilage anatomy and physiology will enable the physician to more fully appreciate its function and necessity. Articular cartilage is made up of four basic biological layers or zones. Each zone possesses attributes necessary to make articular cartilage as a whole strong, durable, and more able to withstand shear and axial forces through a joint. Cartilage metabolism is relatively slow in comparison with other tissues; hence, it is much more difficult for defects in cartilage to heal spontaneously. There are many ways in which articular cartilage can incur damage. Mechanical injury, be it acute or insidious, causes cartilage to fissure and fracture. This results in painful and inflamed joints along with disruption of the cartilage. Metabolic diseases also can produce joint destruction, inflammation, and pain. The resultant defects fail to heal spontaneously because of slow metabolism of cartilage. These chondral defects eventually may penetrate subchondral bone. Disruption of the layers of cartilage eventually will cause collapse and loss of integrity of the entire joint apparatus as a whole. More than 250 years ago, Hunter stated, "Ulcerated cartilage is a troublesome thing--once [it is] destroyed it is not repaired." Articular cartilage defects are very difficult to repair effectively. Cartilage defects can heal spontaneously, if the defect extends to subchondral bone. The reparative substance, fibrocartilage, is less durable and much less smooth. There are many techniques and procedures in which chondral or osteochondral defects can be filled. Promoting subchondral bleeding is the method most commonly used clinically. This allows pleuripotent cells to fill the defect with eventual fibrocartilage. Implants are gaining favor as a method of inducing a more pure, hyaline-like cartilage into cartilage defects. Gene therapy and tissue engineering are at the forefront of cartilage research today. Cartilage injury and repair remains today a very difficult topic of study. Understanding the anatomy of articular cartilage, the pathomechanics of injury, and methods available for cartilage repair, will help the physician more adequately approach treatment options.     

关节软骨缺损修复研究进展

关节软骨缺损是临床常见疑难病症之一。滑膜关节表面缺损后难以修复。现就关节软骨缺损的自发修复、自体或异体移植修复、软骨膜或骨膜移植修复、软骨细胞移植修复，以及三维立体细胞培养及组织工程技术修复等五个方面，综述了滑膜关节软骨缺损修复重建的方法学进展     

Chondrogenesis in Repair of Articular Cartilage Defects by Free Periosteal Grafts in Rabbits

The origin of the cartilaginous tissue in articular defects after periosteal grafting was studied histologically in 6-month-old rabbits. The grafts were taken from the tibia and transplanted to artificial defects in the femoral articular cartilage. An isolating Nucleopore filter^®, hindering the penetration of cells, was placed between the graft and the cancellous bone, in order to trace the origin of the proliferating cells. The histological results revealed that the cartilage tissue which proliferated in the defect originated from the periosteal graft and not from the subchondral bone. The effect of the depth of the defect was studied by making a superficial and deep part in the defect. Cartilage tissue was found in both parts of the defect, though there was less in the more superficial defect.     

软骨组织工程支架材料研究进展

各种原因引起的关节软骨损伤在临床工作中非常常见,但临床治疗手段有限,组织工程的发展为关节软骨损伤的修复提供了新的途径。在软骨组织工程中支架材料起着重要作用,选择合适的载体是一个首先要解决的问题。本文对目前软骨组织工程支架材料的现状做一综述,指出了当前软骨组织工程所面临的问题,并针对此问题对未来软骨组织工程材料的研究作出了展望。     

同种异体组织工程化软骨修复关节软骨缺损

目的　探讨应用同种异体组织工程化软骨修复软骨缺损的可行性。方法　取新西兰大白兔双膝关节软骨细胞 ,经体外培养扩增 ,与PlruonicF12 7混合 ,植入人为造成的异体兔膝关节软骨缺损。结果　空白对照组和材料对照组只见少许纤维组织修复 ,缺损凹陷 ;实验组 8周后关节软骨缺损区由部分白色透明样软骨组织充填 ,Masson三色染色见胶原分布较均匀 ,软骨陷窝多见 ,未见明显炎症现象。 16周后缺损完全修复 ,缺损表面较光滑 ,部分颜色呈淡兰色 ,软骨陷窝清晰 ,细胞与基质分布均匀 ,未见炎症和退变现象。结论　同种异体组织工程化软骨可用于修复关节软骨缺损。     

Repair of articular cartilage defects with cultured chondrocytes in Atelocollagen gel

We attempted to repair full-thickness articular cartilage defects in rabbit knee joints with allogeneic cultured chondrocytes embedded in Atelocollagen gel. An articular cartilage defect was created on the patellar groove of the femur. The defect was filled with chondrocytes cultured in the collagen gel and covered with periosteal flap (G group). In three other experimental groups, the same defects were transplanted with chondrocytes in monolayer culture with periosteal flap (M group), periosteal graft only (P group), or left empty (E group). At 4, 12, and 24 weeks after operation, the reparative tissue was analyzed macroscopically and histologically. At 4 weeks after operation, the surfaces of the reparative tissue were smooth, and the defects were filled with reparative tissues that resembled hyaline cartilage in all four groups. However, the reparative tissues degenerated gradually with time in the M, P, and E groups. In contrast, in the G group, the reparative tissue retained its thickness, and there was a steady integration of the grafted tissue into the adjacent normal cartilage at 24 weeks after operation. The results suggest that transplantation of allogeneic chondrocytes cultured in Atelocollagen gel is effective in repairing an articular cartilage defect.     

Treatment of focal articular cartilage lesions of the knee with autogenous osteochondral grafts

A retrospective study of 15 patients with 16 knees who underwent osteochondral autografts for focal full thickness articular cartilage defects of the knee with 2- to 4-year follow-up showed 80% good or excellent clinical results. There was no correlation of the clinical results with the underlying diagnoses, including osteonecrosis, osteochondritis dessicans and traumatic cartilage defect, or a size of the lesion smaller than 600 mm(2). However, cartilage lesions larger than 600 mm(2) were associated with increasing fibrous tissue formation and fissuring between the grafts and the host tissues and poor results. The improvement in symptoms appeared time-dependent, ranging from 6 to 16 weeks, suggesting that postoperative protection of the graft is warranted. There was no radiographic progression of degenerative changes of the knee on the medium-term follow-up. Therefore, an autogenous osteochondral graft is considered a good method in the treatment of knees with moderately sized articular cartilage defects.     

Repair of articular cartilage defects with cultured chondrocytes on polysulphonic membrane: experimental studies in rabbits

INTRODUCTION: Autologous osteochondral transplantation is one method that can be used to create hyaline or hyaline-like repair in a defect area. The purpose of the present study was to repair full-thickness articular cartilage defects in 9 rabbit knee joints with autologous cultured chondrocytes. METHODS: An articular cartilage defect was created on the patellar groove of the femur. The defect was filled with chondrocytes cultured in vitro and placed into the knee on a polysulphonic membrane. At 8 weeks after the operation, the reparative tissue was analyzed macroscopically and histologically. RESULTS: At 8 weeks after the operation, the surfaces of the reparative tissue were smooth, and the defects were filled with mature hyaline cartilage in 5 cases. In 2 cases, the reparative hyaline cartilage was immature and there was worse integration of grafted tissue into the adjacent normal cartilage. In 2 cases, the surface of the grafted area was irregular, and the reparative tissue was disintegrated and incompletely differentiated. CONCLUSION: The results suggest that transplantation of autologous chondrocytes cultured in vitro and placed into the knee on polysulphonic membrane is effective in repairing an articular cartilage defect.     

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。