Osteochondritis dissecans of the talus treated by the transplantation of tissue-engineered cartilage

Management of osteochondral lesions of the joint has been difficult, because articular cartilage has a poor healing capacity as a result of its lack of vessels, nerve supply, and its isolation of systemic regulation. Although a lot of basic research and surgical treatments for cartilage repair have focused on osteochondral lesions in the knee joint, orthopedic surgeons have recently diverted their attention to osteochondral lesions in the ankle joint, partly because of the widespread introduction of arthroscopy in ankle surgery. There have been many attempts to treat articular cartilage defects in the ankle joint as well as in the knee joint. However, no treatment has achieved efficient healing with hyaline cartilage. Recently, tissue engineering technique for cartilage repair has been gaining much attention in the orthopedic field. In this study, we reported on a patient with osteochondritis dissecans of the talar dome, successfully treated by transplantation of tissue-engineered cartilage made ex vivo using atelocollagen gel and low tibial osteotomy.     

The osteochondral dilemma: review of current management and future trends

The management of articular cartilage defects remains challenging and controversial. Hyaline cartilage has limited capacity for self‐repair and post‐injury cartilage is predominantly replaced by fibrocartilage through healing from the subchondral bone. Fibrocartilage lacks the key properties that characterize hyaline cartilage such as capacity for compression, hydrodynamic permeability and smoothness of the articular surface. Many reports relate compromised function associated with repaired cartilage and loss of function of the articular surface. Novel methods have been proposed with the key aim to regenerate hyaline cartilage for repair of osteochondral defects. Over the past decade, with many exciting developments in tissue engineering and regenerative cell‐based technologies, we are now able to consider new combinatorial approaches to overcome the problems associated with osteochondral injuries and damage. In this review, the currently accepted surgical approaches are reviewed and considered; debridement, marrow stimulation, whole tissue transplantation and cellular repair. More recent products, which employ tissue engineering approaches to enhance the traditional methods of repair, are discussed. Future trends must not only focus on recreating the composition of articular cartilage, but more importantly recapitulate the nano‐structure of articular cartilage to improve the functional strength and integration of repair tissue.     

组织工程技术修复同种异体兔关节软骨缺损实验研究

目的：探讨关节软骨缺损治疗的新途径。方法：把几丁糖作为软骨细胞培养的支架。将几丁糖与软骨细胞一起体外培养,然后移植修复同种异体兔的膝关节软骨缺损,并对关节软骨的修复过程进行术后16周大体、组织学、电镜观察及修复组织厚度测定。结果：几丁糖无纺网在术后2周开始降解吸收,术后10-12周完全吸收;术后第16周在实验侧关节软骨缺损处可见成熟的透明软骨,软骨缺损得到完全修复。结论：几丁糖泊生物学特性符合组织工程中对细胞培养支架的要求;几个糖负载软骨细胞移植修复同种异体兔膝关节软骨缺损,兔膝关节全层软骨缺损得到成功修复。为临床上关节软骨缺损的治疗提供了可能的途径。     

Variation of cell and matrix morphologies in articular cartilage among locations in the adult human knee

OBJECTIVE: Understanding of articular cartilage physiology, remodelling mechanisms, and evaluation of tissue engineering repair methods requires reference information regarding normal structural organization. Our goals were to examine the variation of cartilage cell and matrix morphology in different topographical areas of the adult human knee joint. METHODS: Osteochondral explants were acquired from seven distinct anatomical locations of the knee joints of deceased persons aged 20-40 years and prepared for analysis of cell, matrix and tissue morphology using confocal microscopy and unbiased stereological methods. Differences between locations were identified by statistical analysis. RESULTS: Medial femoral condyle cartilage had relatively high cell surface area per unit tissue volume in the superficial zone. In the transitional zone, meniscus-covered lateral tibia cartilage showed elevated chondrocyte densities compared to the rest of the knee while lateral femoral condyle cartilage exhibited particularly large chondrocytes. Statistical analyses indicated highly uniform morphology throughout the radial zone (lower 80% of cartilage thickness) in the knee, and strong similarities in cell and matrix morphologies among cartilage from the femoral condyles and also in the mediocentral tibial plateau. Throughout the adult human knee, the mean matrix volume per chondron was remarkably constant at approximately 224,000 microm(3), corresponding to approximately 4.6 x 10(6) chondrons per cm(3). CONCLUSIONS: The uniformity of matrix volume per chondron throughout the adult human knee suggests that cell-scale biophysical and metabolic constraints may place limitations on cartilage thickness, mechanical properties, and remodelling mechanisms. Data may also aid the evaluation of cartilage tissue engineering treatments in a site-specific manner. Results indicate that joint locations which perform similar biomechanical functions have similar cell and matrix morphologies; findings may therefore also provide clues to understanding conditions under which focal lesions leading to osteoarthritis may occur.     

Chondrozyten – ein Zelltyp, verschiedene Subpopulationen

Chondrocytes represent the most important cell source for engineering of cartilaginous tissues. Depending on the tissue type and the localization within the tissue, these cells may behave differently. Numerous studies have been done to compare articular, nasal, auricular, and costal chondrocytes in order to evaluate differences between knee and ankle joint cartilage and to investigate topographical variations within an articular joint. Moreover, the zonal structure of articular cartilage needs to be considered because it leads to phenotypical differences between chondrocytes of the superficial and the deeper zones. Several studies indicate, however, that even differentiated chondrocytes demonstrate a certain plasticity and strive to adapt their phenotypes to a new mechanical and biochemical environment. The aim of this review is to report on similarities and differences of chondrocytes from different tissues, zones, and topographical locations. In particular, an overview of recent results from comparative studies is presented, and possible consequences for the design of tissue engineering models are discussed.     

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。     

Biologic approaches to articular cartilage surgery: future trends

The treatment of unicompartmental osteoarthritis and focal chondral pathologic conditions in the knee in active aging athletes has captured the interest of patients, clinicians, basic scientists, and medical industry researchers. Most would agree that a biologic solution to treating hyaline cartilage injuries and degeneration would be optimal over prosthetic joint arthroplasty. Articular cartilage resurfacing techniques and biologic surgical methods continue to evolve and have gained more acceptance in orthopedic practice. A consensus exists for the ultimate goal of achieving a more predictable and durable result after surgical tissue repair or regeneration. Numerous promising approaches are now on the horizon and although the final word is far from in, the integration of many of the anticipated advances in molecular medicine, biomedical engineering, polymer chemistry, cell biology, and clinical orthopedics contributes to an exciting and rapidly evolving field. This article reviews the current concepts of the biologic approach to articular cartilage pathologic conditions and discusses future trends and novel technologies.     

关节软骨组织工程支架的研究进展

目的对软骨组织工程支架材料的研究现状进行综述,并对其发展前景进行展望。方法广泛查阅近年来关节软骨组织工程支架的相关文献,并对多种天然生物支架材料和人工合成支架材料的相关实验及临床应用效果进行分析总结。结果软骨组织工程支架的设计对软骨组织损伤修复成功与否至关重要,理想的软骨支架可以引导并促进新生软骨组织的形成。目前所应用的支架材料均有其局限性。结论进一步深入研究软骨组织工程支架,对未来临床软骨损伤的修复具有重要意义。     

Articular cartilage repair & joint preservation: A review of the current status of biological approach

The articular cartilage of the joint is the thin viscoelastic layer of the connective tissue. It has a unique anatomy and physiology, which makes the repair of the articular cartilage damage more difficult and challenging due to its limited healing capacity. Increasing knowledge regarding the importance of articular cartilage for joint preservation has led to increased attention on early identification of cartilage damage as well as degeneration in order to delay osteoarthritis. There are various treatment modalities ranging from preventive management, physical therapy, pharmacological, non-pharmacological and surgical treatments exist in current literature. However most of the studies have limited long term follow up and mainly consists of small case series and case reports. This is an up to date concise review discussing the available management options for articular cartilage damage starting to lifestyle modification to pharmacotherapy, physiotherapy, and osteobiologics till various joint preservation techniques that have been in use currently.     

Editorial Commentary: Early Postoperative Knee Joint Space Width Change Is Attributable to Change in the Joint Line Convergence Angle After High Tibial Osteotomy and May Not Reflect Cartilage Regeneration

Realignment of the weightbearing axis by high tibial osteotomy (HTO) can alter the forces acting on the articular cartilage within the knee, reducing the load on the medial compartment. This unloading effect is thought to allow the repair of the articular cartilage of the affected compartment. It is important to evaluate the serial changes of joint space width (JSW) after HTO for assessing the state of the cartilage and the unloading effect by HTO. However, early postoperative knee JSW change is attributable to change in the joint line convergence angle after HTO and may not reflect cartilage regeneration. In addition, the soft tissue laxity of the knee and changes in joint line convergence angle after HTO should be considered for assessing these early postoperative JSW changes.     

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。     

软骨脱细胞基质-Ⅱ型胶原纳米支架复合BMSC修复兔关节软骨缺损的实验研究

目的 观察软骨脱细胞基质(Cartilage acellular extracellular matrix,CAEM)-Ⅱ型胶原(CollagenⅡ,COLⅡ)纳米支架,复合骨髓基质干细胞(Bone marrow stem cells,BMSCs)修复兔关节软骨缺损的效果。方法 CAEM和COLⅡ按质量比1∶1混合,通过静电纺丝技术制备组织工程纳米支架。将第二代BMSCs种植到该支架上,培养箱内静置2 h。12只日本大耳白兔随机分为实验组和对照组,将细胞支架复合物植入实验组兔膝关节软骨缺损处,对照组仅行膝关节软骨缺损建模。12周后实验动物取材,大体观察修复效果,并行HE染色、Ⅱ型胶原染色观察。结果 大体观察见实验组软骨缺损修复良好,对照组软骨缺损处由肉芽样组织充填。HE染色显示,实验组关节软骨缺损处可见软骨陷窝形成,对照组关节软骨缺损处仅有纤维组织充填。实验组修复区Ⅱ型胶原染色为阳性,对照组为阴性。结论 CAEM-COLⅡ纳米支架复合BMSC,对兔关节软骨缺损具有较好的修复能力,具有潜在的临床应用价值。     

Skeletal tissue regeneration: where can hydrogels play a role?

The emerging field of tissue engineering reveals promising approaches for the repair and regeneration of skeletal tissues including the articular cartilage, bone, and the entire joint. Amongst the myriad of biomaterials available to support this strategy, hydrogels are highly tissue mimicking substitutes and thus of great potential for the regeneration of functional tissues. This review comprises an overview of the novel and most promising hydrogels for articular cartilage, osteochondral and bone defect repair. Chondro- and osteo-conductive and -instructive hydrogels are presented, highlighting successful combinations with inductive signals and cell sources. Moreover, advantages, drawbacks, and future perspectives of the role of hydrogels in skeletal regeneration are addressed, pointing out the current state of this rising approach.     

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.     

Articular cartilage repair using tissue engineering technique--novel approach with minimally invasive procedure

Articular cartilage has very limited potential to spontaneously heal, because it lacks vessels and is isolated from systemic regulation. Although there have been many attempts to treat articular cartilage defects, such as drilling, microfracture techniques, soft tissue grafts or osteochondral grafts, no treatment has managed to repair the defects with long-lasting hyaline cartilage. Recently, a regenerative medicine using a tissue engineering technique for cartilage repair has been given much attention in the orthopedic field. In 1994, Brittberg et al. introduced a new cell technology in which chondrocytes expanded in monolayer culture were transplanted into the cartilage defect of the knee. As a second generation of chondrocyte transplantation, since 1996 we have been performing transplantation of tissue-engineered cartilage made ex vivo for the treatment of osteochondral defects of the joints. This signifies a concept shift from cell transplantation to tissue transplantation made ex vivo using tissue engineering techniques. We have reported good clinical results with this surgical treatment. However, extensive basic research is vital to achieve better clinical results with this tissue engineering technique. This article describes our recent research using a minimally invasive tissue engineering technique to promote cartilage regeneration.     

Proteoglycan alterations during developing experimental osteoarthritis in a novel hip joint model

Degenerative hip joint disease was induced in dogs by extra-articular surgery that created a condition that mimics hip dysplasia. Decreased acetabular coverage of the femoral head gave altered mechanical load, with ensuing cartilage degeneration. For comparison, degenerative knee joint disease was induced in other dogs by transection of the anterior cruciate ligament of the knee. The femoral head articular cartilage showed macroscopic signs of degeneration within a month. No macroscopical changes of synovitis were present. Chemical analysis of cartilage samples showed loss of proteoglycans. Guanidine hydrochloride extracts of the cartilage contained proteoglycan fragments that could be separated by equilibrium density gradient centrifugation in cesium chloride. The data indicate that proteoglycans are fragmented by proteolytic cleavage and lost from the cartilage. The proteoglycans remaining in the tissue are smaller and have lost the ability to aggregate with hyaluronic acid. Similarly, in experimental knee joint osteoarthritis, the proteoglycan content of the cartilage decreased. The structural changes of those proteoglycans remaining were of a different nature, with no changes in proteoglycan size or aggregation properties, possibly indicating that both degradation and repair took place in the knee articular cartilage and/or that fragments were rapidly lost from the tissue. This may follow from different surgical procedures, only the one used for the hip joint being extra-articular, or from the different anatomy and physiology of the hip joint and the knee joint.     

不同来源间充质干细胞在膝关节软骨修复中的临床研究进展

近年来由于器官修复干细胞治疗技术的提出,使得不能自身修复的关节软骨成为研究热点之一,间充质干细胞对膝关节软骨修复已表现出明显的治疗优势。学者们临床上初步研究了不同来源的间充质干细胞膝关节软骨修复作用,并通过结合移植、软骨组织工程等技术提高了骨髓、脂肪、滑膜、脐带血等来源干细胞修复人类软骨效果,均取得了较好的临床疗效。不同干细胞来源不同各自会有一定的优缺点。目前临床研究仍处于试验阶段,尚无确切定论何种干细胞及何种技术处理最适合于人类软骨的修复。大规模和或结合新处理技术的临床试验以及远期疗效的验证,需要进一步临床深入研究。     

Management of focal cartilage defects in the knee - Is ACI the answer?

Injuries to the articular cartilage of the knee are common. They alter the normal distribution of weightbearing forces and predispose patients to the development of degenerative joint disease. The management of focal chondral lesions continues to be problematic for the treating orthopaedic surgeon. Although many treatment options are currently available, none fulfill the criteria for an ideal repair solution: a hyaline repair tissue that completely fills the defect and integrates well with the surrounding normal cartilage. Autologous chondrocyte implantation (ACI) is a relatively new cell-based treatment method for full-thickness cartilage injuries that in recent years has increased in popularity, with early studies showing promising results. The current article reviews the nature of cartilage lesions in the knee and the treatment modalities utilized in their management, focusing on the role ACI plays in the surgical treatment of these complex injuries.     

Stimulation of ankle cartilage: other emerging technologies (cellular, electricomagnetic, etc.)

Advances in understanding age-related changes in articular cartilage, joint homeostasis, the natural healing process after cartilage injury, and improved standards for evaluation of a joint surface made the ultimate goal of cartilage repair a possibility. New strategies for enhancement of articular cartilages' limited healing potential and biologic regeneration include advances in tissue engineering and the use of electromagnetic fields. This article reviews developments in basic science and clinical research made with these emerging technologies concerning treatment of articular cartilage defects and treatment of osteoarthritis of the ankle.     

Gene therapy for cartilage repair

AIM: Articular cartilage has very limited intrinsic healing capacity. Although numerous attempts to repair full-thickness articular cartilage defects have been conducted, no methods have successfully regenerated long-lasting hyaline cartilage. One of the most promising procedures for cartilage repair is tissue engineering accompanied by gene therapy. METHOD: With gene therapy, genes encoding for therapeutic growth factors can be expressed at a high level in the injured site for an extended period of time. Chondrocytes have been intensively studied for cell transplantation in articular cartilage defects. RESULTS: However, recent studies have shown that chondrocytes are not the only candidate for cartilage repair. Muscle-derived cells have been found capable of delivering genes and represent a good vehicle to deliver therapeutic genes to improve cartilage repair. More importantly, recent studies have suggested the presence of pluripotent stem cells in muscle-derived cells. CONCLUSION: New techniques of cell therapy and molecular medicine for the treatment of cartilage lesions are currently undergoing clinical trials. This paper will summarize the current status of gene therapy for cartilage repair and its future application.