The Healing of Cartilage Injuries Under the Influence of Joint Immobilization and Repeated Hyaluronic Acid Injections: An Experimental Study

In an experimental animal model the influence of intraarticularly injected high-molecular hyaluronic acid on the healing of superficial and deep lesions of the articular cartilage in freely mobile and immobilized joints was investigated. In the right knee joint in 42 adult rabbits two intracartilaginous lesions were produced in one of the femoral condyles and an osteochondral lesion in the other. In half of the animals the injured knee joint was immobilized in plaster of Paris, while the other half were allowed to move the joint freely. Half of the injured joints in each group were then injected with high-molecular hyaluronic acid once a week for 8 weeks. After 2 months the knee joints were examined histologically, histochemically and microangio-graphically and the water content of the articular cartilage was determined. The intracartilaginous lesions remained unchanged in all knee joints. The wound margins of the osteochondral lesions showed better closure in the immobilized animals. As a rule the osteochondral lesion healed with fibrous connective tissue. In a few joints, however, hyaline cartilage, with production of chondroitin sulphate, developed during healing of the osteochondral lesion. In the vicinity of the joint surface this tissue was transformed into fibrocartilage. Immobilization of the joint invariably led to pannus formation. The hyaluronic acid injections appeared to have no effect, either positive or negative, on the healing of intracartilaginous and osteochondral joint lesions. In mobile joints, however, these injections prevented a reduction of the water content of the articular cartilage, which was regarded as favourable.     

Bony Lesion Recurrence After Mosaicplasty for Osteochondritis Dissecans of the Talus

Autogenous osteochondral grafts have recently become popular for use in small, isolated, contained articular cartilage defects. We treated a 26-year-old man who had a cartilage defect measuring 10 × 20 mm in the anteromedial area of the right talus. We performed multiple osteochondral grafting of the lesion with medial malleolar osteotomy from a donor site in the ipsilateral knee joint. Two years after the operation, the patient’s ankle pain recurred and the bony lesion in the talus also became osteolytic. Because we believed that only the cartilaginous portions of the osteochondral plugs grafted 2 years previously were fully fixed and viable, and that recurrence had occurred at the bony portions, at reoperation we performed curettage of the bony lesions and grafted iliac bone into the lesions with fenestration of the inferomedial ankle joint cartilage, not grafted plug cartilage. Therefore, probably because of overuse, the bony lesion in the talus had recurred 2 years after the first operation, but the grafted hyaline cartilage had survived. Autogenous osteochondral grafting into the talus, unlike the knee joint, should be done with care to ensure there is no sclerotic bone surrounding the lesion in patients with long-standing symptoms and recurrence of bony lesions.     

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.     

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.     

Osteochondral allograft transplantation in the knee

Fresh osteochondral allograft (OCA) transplantation has over a 100-year clinical history. Many clinical and basic scientific studies have been performed with the result that allografting is now a part of the "cartilage repair paradigm" for the treatment of chondral or osteochondral lesions. In the knee joint, allografting has also been successfully used in complex joint reconstruction for the treatment of osteonecrosis, fracture malunion, and selected cases of osteoarthritis. Unlike many other cartilage repair techniques, OCA have the ability to restore mature, hyaline articular cartilage to the affected area. By virtue of their composite structure (cartilage and bone), allografts also can restore diseased or damaged bone often present in large or complex lesions. Nevertheless, OCA present unique and important difficulties in their clinical application, such as allograft tissue availability, safety issues, and immunologic response to the graft. Ongoing investigations continue to clarify the indications, surgical techniques, and clinical outcomes of fresh OCA.     

Clinical relevance of scaffolds for cartilage engineering

The repair of articular cartilage defects in patients' knees presents a particular challenge to the orthopedic surgeon because cartilage lacks the ability to repair or regenerate itself. Various cartilage repair techniques have not produced a superior or uniform outcome, which has led to a new generation of cartilage repair based on tissue-engineering strategies and the use of biological scaffolds. Clinical advances have been made regarding the regeneration of articular cartilage, and continue to be made toward the achievement of a suitable treatment method for resurfacing osteochondral defects, through cartilage tissue engineering and the use of pluripotent cells seeded on bio-scaffolds.     

Editorial Commentary: Osteochondral Lesions of the Talus: All,Nothing, or Something in Between

Osteochondral lesions of the talus occur with relatively frequency, often as the sequelae of benign ankle sprains, and are only surpassed by the knee and elbow as more common locations. While microfracture of the talus is the most common first-line surgical treatment performed at the time of ankle arthroscopy, marrow stimulation alone results in fibrocartilaginous repair tissue rather than true hyaline-like articular cartilage. In addition, the benefits of bone marrow stimulation for the treatment of large (>150 mm²), deep (>7 mm), or cystic lesions is limited. Autologous osteochondral transplant has emerged as one such treatment option for large lesions that may address underlying bone loss and reconstitute articular cartilage. The utility of autologous osteochondral transplant also must be interpreted with an understanding of the potential complications, including donor-site morbidity. In addition, it is important to decompress, curettage, and back fill associated cysts with bone graft. When cysts are not treated aggressively, patients may have ongoing bone marrow edema and pain.     

Osteotomies in the treatment of osteochondral lesions of the knee joint

Excellent results of total knee arthroplasty have outweighed high tibial osteotomy applications in the treatment of osteoarthritis of the knee joint, but there is a growing interest in osteotomies as an adjunct in the treatment of full-thickness chondral and osteochondral lesions of the knee. Abnormal biomechanics in both tibiofemoral and patellofemoral articulations resulting from instability and malalignment should be corrected and osteotomy should be regarded as the first step in the treatment of these lesions. A simultaneous or staged osteotomy may contribute to the success of current techniques used for cartilage and osteochondral repair. Clinical, radiographic, and experimental studies have shown beneficial effects of osteotomies on cartilage regeneration. The aim of the osteotomy is simple: cartilage needs proper biomechanical environment for healing.     

The detached osteochondral fragment as a source of cells for autologous chondrocyte implantation (ACI) in the ankle joint

OBJECTIVE: Autologous chondrocyte implantation (ACI) has been successfully used for the treatment of osteochondral lesions of the talus. One of the main problems of this surgical strategy is related to the harvesting of the cartilage slice from a healthy knee. The aim of this study was to examine the capacity of chondrocytes harvested from a detached osteochondral fragment to proliferate and to serve as a source of viable cells for ACI in the repair of ankle cartilage defects. METHODS: Detached osteochondral fragments harvested from the ankle joint of 20 patients with osteochondral lesions of the talus served as the source of human articular cartilage specimens. All of the osteochondral lesions were chronic and of traumatic origin. In all cases, the fragments were utilized to evaluate the viability and proliferation of the cells, the histological appearance of the cartilage tissue and the expression of specific cartilage markers by real-time polymerase chain reaction (PCR). In the 16 patients scheduled for ACI, the expanded chondrocytes were used for chondrocyte implantation. In the other 4 patients, with lesion size <1.5cm(2), microfractures were created during the initial arthroscopic step. As a control group, 7 patients with comparable osteochondral lesions underwent the same surgery, but received chondrocytes harvested from the ipsilateral knee. RESULTS: According to the American Orthopaedic Foot and Ankle Scoring (AOFAS) system, patients in the experimental group had a preoperative score of 54.2+/-16 points and a postoperative one of 89+/-9.6 points after a minimum follow-up time of 12 months (P<0.0005). The control group of patients had a preoperative score of 54.6+/-11.7 points and a postoperative one of 90.2+/-9.7 points at a minimum follow-up time of 12 months (P<0.0005). The clinical results of the two groups did not differ significantly from each other. Chondrocytes isolated from the detached fragments were highly viable, phenotypically stable, proliferated in culture and redifferentiated when grown within the three-dimensional scaffold used for ACI. The morphological and molecular characteristics of the cartilage samples obtained from the detached osteochondral fragments were similar to those of healthy hyaline articular cartilage. CONCLUSIONS: The good results achieved with this strategy indicate that cells derived from the lesioned area may be useful in the treatment of osteochondral defects of the talus.     

Lateral Compartment Osteoarthritis of the Knee After Meniscectomy Treated by the Transplantation of Tissue-Engineered Cartilage and Osteochondral Plug

Management of osteoarthritis of the knee after meniscectomy has been challenging, especially for young patients, because articular cartilage has very poor healing capacity because of its lack of vessels, nerve supply, and isolation from systemic regulation. Osteoarthritic lesions often involve both femoral and tibial cartilage, requiring treatments for both lesions. We report the case of a 14-year-old girl with lateral compartment osteoarthritis of the knee after a total meniscectomy of the discoid meniscus, who was successfully treated by the transplantation of both tissue-engineered cartilage made ex vivo for a femoral lesion and an autologous osteochondral plug for a tibial lesion. We treated both femoral and tibial cartilage defects simultaneously with this procedure. We confirmed cartilaginous regeneration in both femoral and tibial lesions at second-look arthroscopy. This procedure is one option to prevent further development of osteoarthritis in young patients.     

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。     

New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review

In this paper review we describe benefits and disadvantages of the established methods of cartilage regeneration that seem to have a better long-term effectiveness. We illustrated the anatomical aspect of the knee joint cartilage, the current state of cartilage tissue engineering, through mesenchymal stem cells and biomaterials, and in conclusion we provide a short overview on the rehabilitation after articular cartilage repair procedures. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, and to date several researchers aim to implement clinical application of cell-based therapies for cartilage repair. A literature review was conducted on PubMed, Scopus and Google Scholar using appropriate keywords, examining the current literature on the well-known tissue engineering methods for the treatment of knee osteoarthritis.     

Injuries to the Articular Cartilage

Abstract Injuries to articular cartilage are commonly encountered in orthopedic sports medicine. These lesions can lead to sport invalidity and premature osteoarthritis. The management of chondral and osteochondral lesions represents a challenge to clinicians and scientists. The aim of the therapy has to be the recurrence to former sport levels and the prevention of early osteoarthritis. Today there are different concepts of treatment. One therapy principle is the recruitment of mesenchymal stem cells. These procedures lead at best to fibrocartilaginous repair tissue that is functionally inferior to normal hyaline cartilage. Another group of procedures is the transplantation of autologous osteochondral grafts, which provide repair with a hyaline cartilage matrix and show good clinical medium-term results. But osteochondral grafts are limited and there is a potential donor-site morbidity. Finally, the transplantation of autologous chondrocytes is used. However, this kind of transplantation repairs the chondral injury only by fibrocartilaginous repair tissue, too. Therefore, new techniques for the treatment of articular cartilage injuries have to be established. The most promising field today is the combination of tissue-engineering and gene therapeutic methods for the treatment of the chondral and osteochondral lesions.     

A review of the differences between normal and osteoarthritis articular cartilage in human knee and ankle joints

BackgroundOsteoarthritis (OA) is the most common joint disease yet its pathophysiology is still poorly understood. It is more prevalent in some lower limb joints than others; in particular the knee is more commonly affected than the ankle. Research into articular cartilage and OA has primarily focussed on using animal models. However, it is apparent that articular cartilage differs between species, so more research is concentrating on human cartilage.ObjectiveThis paper reviews recent studies that have been undertaken to elucidate the reasons for this, and to discover if the findings would alter the conception that articular cartilage is not capable of repair.MethodPrimary research papers into human knee and ankle cartilage published since 1997 have been reviewed.ResultsDifferences in the structure, metabolism, physical properties and response to trauma have been found, implying that ankle cartilage may be more resistant to damage.ConclusionsMore research is needed before definitive conclusions can be reached, but the findings so far suggest that OA should not be accepted as the inevitable outcome of joint injury and individuals and practitioners, such as podiatrists, may be able to use simple measures to prevent or delay its onset.     

Osteochondral autologous transplantation in various joints

A chondral/osteochondral defect involving the articular surface of a joint is still a therapeutic problem. The goal of articular cartilage repair is restoration of cartilage congruity, accomplishing full painfree range of motion and elimination of cartilage detoriation. The use of autologous grafts was first reported by Wagner 1964. Now the use of cylindrical autograft plugs was described by Bobic 1996 and Hangody 1996. Operative management and early results of osteochondral cylindrical autograft plugs in the femoral condyle, patella, elbow and talar dome are presented. The arthroscopic/open use of autologous osteochondral grafts from the knee is indicated in osteochondral lesions in diameter from 1 to 3 cm, which can not be primarily refixed and in osteonecrosis at femoral condyle, patella, elbow, talar dome as well as shoulder.     

Diagnosing,planning and evaluating osteochondral ankle defects with imaging modalities

This current concepts review outlines the role of different imaging modalities in the diagnosis, preoperative planning, and follow-up of osteochondral ankle defects. An osteochondral ankle defect involves the articular cartilage and subchondral bone (usually of the talus) and is mostly caused by an ankle supination trauma. Conventional radiographs are useful as an initial imaging tool in the diagnostic process, but have only moderate sensitivity for the detection of osteochondral defects. Computed tomography (CT) and magnetic resonance imaging (MRI) are more accurate imaging modalities. Recently, ultrasonography and single photon emission CT have been described for the evaluation of osteochondral talar defects. CT is the most valuable modality for assessing the exact location and size of bony lesions. Cartilage and subchondral bone damage can be visualized using MRI, but the defect size tends to be overestimated due to bone edema. CT with the ankle in full plantar flexion has been shown a reliable tool for preoperative planning of the surgical approach. Postoperative imaging is useful for objective assessment of repair tissue or degenerative changes of the ankle joint. Plain radiography, CT and MRI have been used in outcome studies, and different scoring systems are available.     

Cartilage repair in the knee joint

Full thickness defects of the articular cartilage in the knee joint have lower regenerative properties compared to chondral lesions of the ankle. In order to avoid early osteoarthritis, symptomatic articular cartilage defects in younger patients should undergo biological reconstruction as early as possible. There are different surgical procedures available to achieve a biological resurfacing of the articular joint line. Numerous animal experiments and clinical studies have shown that early biological reconstruction of circumscribed cartilage defects in the knee is superior to a conservative or delayed operative treatment. This effect refers not only to the defect healing but also to the elimination of changes following secondary osteoarthritis. The different surgical procedures can be differentiated concerning the various indications and the final outcome. Additional malalignment, meniscus tears, and/or ligament instabilities should be treated simultaneously together with the cartilage resurfacing. The mid- and long-term results of the different current techniques are promising, but further modifications and improvements are needed.     

Articular cartilage defects in the knee--basics, therapies and results

Full-thickness defects of the articular cartilage in the knee joint have lower regenerative properties than chondral lesions of the ankle. In order to avoid early osteoarthritis, symptomatic articular cartilage defects in younger patients should undergo biological reconstruction as soon as possible. Various surgical procedures are available to biologically resurface the articular joint line. Numerous animal experiments and clinical studies have shown that early biological reconstruction of circumscribed cartilage defects in the knee is superior to conservative or delayed surgical treatment. This superiority refers not only to defect healing but also to the elimination of changes following secondary osteoarthritis. The various surgical procedures can be differentiated by the range of indications and the final outcome. Additional malalignment, meniscus tears and/or ligament instabilities should be treated simultaneously with the cartilage resurfacing. The mid- and long-term results of the various current techniques are promising, but further modifications and improvements are needed.     

Cartilage repair of the talus

The cause of a typical osteochondral lesion of the talus is traumatic; if symptomatic, several options exist. Because nonoperative treatment results in no more than 50% good to excellent results, the following types of surgery are in clinical use: (1) debridement and drilling, (2) osteochondral transfer, and (3) autologous chondrocyte transplantation. Reported good to excellent results are at least 80% in the short term. Currently available data allow no recommendation of a specific therapy for a specific lesion. Advocates of drilling and debridement accept that the repair tissue is fibrocartilage; osteochondral transfer includes a donor side morbidity. We are still at the beginning of cartilage repair; it will take time before a certain type of lesion can be treated with the best modality because that requires comparative randomized prospective studies with a long follow-up. All modern cartilage repair techniques, that were initially investigated at the knee joint, are now in use for ankle osteochondral lesions. Reported short-term success rates are greater than 80%. Further improvements will depend on the understanding of the pathogenesis and the role of contributing factors (eg, instability).     

Arthroskopische Behandlung von Knorpelverletzungen am Sprunggelenk

Ankle sprains are the most relevant injuries of the lower extremities and can lead to damage to ligaments and osteochondral lesions. Up to 50?% of patients with a sprained ankle later develop a lesion of the cartilage in the ankle joint or an osteochondral lesion of the talus. This can lead to osteoarthritis of the injured ankle joint. Spontaneous healing is possible in all age groups in cases of a bone bruise in the subchondral bone but in isolated chondral injuries is only useful in pediatric patients. In many cases chondral and osteochondral injuries lead to increasing demarcation of the affected area and can result in progressive degeneration of the joint if not recognized in time. There also exist a certain number of osteochondral changes of the articular surface of the talus without any history of relevant trauma, which are collectively grouped under the term osteochondrosis dissecans. Perfusion disorders are discussed as one of many possible causes of these alterations. Nowadays, chondral and osteochondral defects can be treated earlier due to detection using very sensitive magnetic resonance imaging (MRI) and computed tomography (CT) techniques. The use of conservative treatment only has a chance of healing in pediatric patients. Conservative measures for adults should only be considered as adjuvant treatment to surgery.