Cartilage Transplantation Research Articles

Repair of articular cartilage lesions in aged chickens by allogeneic transplantation of fresh embryonic epiphyses

The potential of fresh whole chick epiphyses of embryonic origin to serve as implant material for cartilage defects of aged chicken was tested. Fresh epiphyses of 11-day-old embryos were collected from 24 animals and transplanted into defects created in the weight-bearing areas of tibiotarsal joint cartilage of 2-year-old chicks. Upon sacrifice, samples were examined macroscopically and microsections were prepared for histology. Macroscopically, control defects remained empty at all the time intervals. Defects of the experimental group were, on the other hand, filled with cartilaginous tissue as early as 2 weeks posttransplantation, although individual epiphyses could still be noted in the implant tissue. At 4 weeks and later, defects were filled with cartilaginous material indistinguishable from hyaline cartilage. Histologically, all grafts remained within the defect's pits, showing mitotic and metabolic activity typical to proliferating hyaline cartilage. The engrafted epiphyses showed a partial incorporation and integration with the surrounding host tissues already at 2 weeks. At 4 weeks and later, the integration was complete. It is concluded that a chick embryonic epiphyseal cartilage is suitable as a graft source for articular cartilage transplantation. The embryonic epiphyses provide immediate inherent stability to the graft and supply a good mix of mesenchymal progenitor cells responsible for the high rate of cell proliferation and adhesion to the differentiated committed chondrocytes of the host that create the typical favorable chondrogenic milieu. Based on the present findings, it is postulated that human embryonic epiphyses may, in the future, represent an alternative source to the commonly used techniques of hyaline cartilage repair.

Bioprosthetic Valves and Laudable Inflammation?

In this issue of Circulation , Dr Manji and colleagues1 from the University of Alberta (Canada) report a series of animal experiments designed to test the mythic role of gluteraldehyde in preventing recognition of bioprosthetic heart valve antigenicity with subsequent rejection and failure. Gluteraldehyde–cross-linked xenograft tissues (initially porcine) have been used in the manufacturing of stented (and now stentless) heart valves since 1970. Original theories for the clinical efficacy of gluteraldehyde were based on its ability to irreversibly cross-link collagen and thus to increase mechanical strength and durability over fresh untanned cardiovascular tissues. Porcine valve leaflets, bovine pericardium, equine pericardium, and bovine jugular vein, among other structures, have been treated this way for clinical applications. Since its introduction, however, limitations and unexpected consequences of gluteraldehyde and similar chemical treatments have been recognized clinically. As pointed out by the authors, durability is quite variable, tending to be better in older patients whereas younger patients suffer early deterioration, calcification, and fibrocalcific failure.2,3 The good news has been that the failures tend to be progressive rather than catastrophic, leading to semielective reoperations. Additionally, the xenograft bioprostheses have been extremely helpful in avoiding warfarin in the very young and the very old, reducing the risk of thromboembolism. The traditional explanation for the fibrocalcific degeneration of the nonvital gluteraldehyde-treated bioprosthetic heart valves has been a combination of physical and chemical effects leading to calcification and a fixation of the structural proteins that prevent protein recycling and renewal. Mechanical theories of fatigue-induced wear resulting in calcification have been proposed, especially along the flexion lines of the cusps. Others have proposed that the gluteraldehyde has serendipitously “masked” the antigenicity of xenograft proteins, retained cells, and cellular debris, thus prolonging the period to calcification. This well-designed series of studies buttresses other studies demonstrating that gluteraldehyde fixation …

The long-term results of meniscus transplantation for articular cartilage defects in the knee joint

The purpose of this study was to examine the long-term clinical results of meniscus transplantation for articular cartilage defects in the knee joint. The type of study was case series. From October 1990 to June 1995, eight cases underwent allogenic or autogenic meniscus transplantations for articular cartilage defects, and seven cases were available for follow-up evaluations. The age at surgery ranged from 14 to 42 years of age (average 22.5). In one case, transplantation of tissue-engineered cartilage was performed due to pain 5 years after surgery. The other six cases were followed up for 8-13 years (average 10.1). The size of the cartilage defect ranged from 1.0 to 6.3 cm2 (average 2.8 cm2). Patients were evaluated with the Lysholm score and MR images. We also performed arthroscopic examinations in three cases at the final evaluation. This study leads to the conclusion that meniscus transplantation for articular cartilage damage is not comparable to autologous chondrocyte transplantation. Two cases showed a good clinical outcome but the tissue remained as fibrocartilage tissue in the long-term.

Allografts in Articular Cartilage Repair

Hyaline articular cartilage is an avascular and insensate tissue with a distinct structural organization, which provides a low-friction and wear-resistant interface for weight-bearing surface articulation in diarthrodial joints. Ideally, articular cartilage is maintained in homeostasis over the lifetime of an individual, with its biomechanical properties inherently suited to transmit a variety of physiologic loads through a functional range of motion. However, in the skeletally mature individual, articular cartilage does not heal effectively when injured. Although several restorative options for biomimetic replacement in acquired articular cartilage defects do exist, fresh osteochondral allografting currently remains the only technique that restores anatomically appropriate, mature hyaline cartilage in large articular defects. The fundamental paradigm of fresh osteochondral allografting is the transplantation of mature orthotopic hyaline cartilage, with viable chondrocytes that survive hypothermic storage and subsequent transplantation while maintaining their metabolic activity and sustaining the surrounding collagen matrix. Fresh osteochondral allografts have application in the treatment of a wide spectrum of articular pathology, particularly conditions that include both an osseous and a chondral component. The surgical procedure for femoral condyle lesions is straightforward but demands precision to achieve reproducible results and to minimize early graft failures related to surgical technique. As with other cartilage-restorative procedures, the indications for use of fresh osteochondral allografts are still being expanded. Many clinical and basic scientific studies support the theoretical foundation and efficacy of small fragment allografting, although more scientific validation of empirical clinical practice is still needed.

Long-term nipple shrinkage following augmentation by an autologous rib cartilage transplant in free DIEP-flaps

Aesthetically pleasing nipple-areola reconstruction is a satisfying part of a two-stage breast reconstruction. The up to 50% [Banducci DR, Le TK, Hughes KC. Long-term follow-up of a modified Anton-Hartrampf nipple reconstruction. Ann Plast Surg 1999;43(5):467-9; discussion 469-70] postoperative shrinkage following a conventional nipple reconstruction is a well-known problem. Augmentation of the nipple with autologous banked cartilage seems to be a promising solution. From 2000-2003, 17 patients underwent a nipple-areola-complex reconstruction following secondary breast reconstruction using free perforator flaps. The rib cartilage harvested during the preparation of the internal thoracic vessels was banked subcutaneously and six months later replanted under the 'arrow flap' after contouring it in a 'mushroom' shape. One year later the shrinkage of the nipple in comparison to the intraoperative status was measured. In addition, patients were asked about their personal palpation impression and the aesthetic outcome. The average height decreased one year postoperatively about 25%. Thirteen of 17 patients judged the aesthetic outcome as very good, 16 nipples healed without cartilage protrusion and no patient felt discomfortable stiffness of the nipple. Our concept of a nipple augmentation with rib cartilage improves the projection and allows a more correct judgement of the later nipple shrinkage. We consider this technique to be an aesthetically satisfying and safe method, which could be used with any kind of breast reconstruction.

Development and phenotypic characterization of a high density in vitro model of auricular chondrocytes with applications in reconstructive plastic surgery.

Cultivation of phenotypically stable auricular chondrocytes will have applications in autologous chondrocyte transplantation and reconstructive surgery of cartilage. Chondrocytes grown in monolayer culture rapidly dedifferentiate assuming a fibroblast-like morphology and lose their cartilage-specific pattern of gene expression. Three-dimensional high-density culture models mimic more closely the in vivo conditions of cartilage. Therefore, this study was undertaken to test whether the high-density cultures might serve as a suitable model system to acquire phenotypically and functionally differentiated auricular chondrocytes from porcine cartilage. Freshly isolated porcine auricular chondrocytes were cultured for 7 passages in monolayer culture. From each passage (passage 0 and 1-7) cells were introduced to high-density cultures and examined by transmission electron microscopy. Western blotting was used to analyse the expression of cartilage-specific markers, such as collagen type II and cartilage specific proteoglycan, fibronectin, cell adhesion and signal transduction receptor beta1-integrin, matrix metalloproteinases (MMP-9, MMP-13), cyclo-oxygenase (COX)-2 and the apoptosis commitment marker, activated caspase-3. When dedifferentiated auricular chondrocytes from monolayer passages 0-4 were cultured in high-density culture, they recovered their chondrocytic phenotype and formed cartilage nodules surrounded by fibroblast-like cells and synthesised collagen type II, proteoglycans, fibronectin and beta1-integrins. However, chondrocytes from monolayer passages 5-7 did not redifferentiate to chondrocytes even when transferred to high-density culture, and did not synthesize a chondrocyte-specific extracellular matrix. Instead, they produced increasing amounts of MMP-9, MMP-13, COX-2, activated caspase-3 and underwent apoptosis. Three-dimensional high-density cultures may therefore be used to obtain sufficient quantities of fully differentiated auricular chondrocytes for autologous chondrocyte transplantation and reconstructive plastic surgery.

Can engineered cartilage transplants be used for treating rheumatic diseases?

There have been many exciting advances in tissue engineering. This Viewpoint discusses the future application of this technology in the chronic rheumatic diseases, focusing on the advantages of methods of cartilage regeneration, such as scaffolds, gels, cell-seeding, fibers or cell cultures.

Treatment of articular cartilage defects in horses with polymer-based cartilage tissue engineering grafts

The objective of our study was to evaluate the integration of autologous cartilage tissue engineering transplants based on resorbable polyglactin/polydioxanone scaffolds into full-thickness cartilage defects of horses. Cartilage biopsies were taken from the non-load-bearing area of the lateral talus of the left tibiotarsal joint of eight healthy Haflinger horses. Tissue engineering cartilage transplants were generated by three-dimensional arrangement of autologous chondrocytes in biocompatible and resorbable polymer scaffolds. Full-thickness cartilage defects of 8 mm in diameter were created in the tubular bone condyle of the fetlock joint and cartilage grafts were fixed using an anchor system, while defects without grafting served as controls. After 6 and 12 months the repair tissue was evaluated histologically and showed formation of a cartilaginous tissue and good integration into the surrounding host tissue with firm bonding of the graft to the adjacent cartilage and the underlying subchondral bone. Biochemical analysis demonstrated that the content of glycosaminoglycans and hydroxyproline is comparable in repair tissue derived from treated and control defects. The use of three-dimensional autologous cartilage transplants based on resorbable polymer scaffolds ensures secure fixation, good integration of the graft into cartilage lesions, and is therefore suggested as a promising therapeutic option for the treatment of cartilage defects.

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.

遊離耳介軟骨移植による鼻中隔穿孔閉鎖術の経験

Nasal septum perforation occurs via many causes such as during surgery head trauma or through systemic disease.Crusting or hemorrhage occurs from the perforated region, and a lot of cases decrease the quality of life of patients remarkably.In addition, a perforation choke operation is chosen for cases whereby control is poor only by conservative treatment such as a topical treatment or chemical administration as therapy. As for the perforation choke operation, various operation methods have been reported. Perforation cause, size, and perforation ambient histionic property vary among cases leading to difficulty in the choice of operation methods.We report one example of nasal septum perforation that we were able to close by isolation via auricular cartilage transplant.The case was a 64 year old woman. The chief complaint was recurrent epistaxis. We completely closed the nasal septum perforation by isolation auricular cartilage transplant and achieved symptomatic improvement.As we were able to close the perforation good cartilaginous survival with the perichondrium was suggested.

Bone and cartilage transplants their use and behaviour

Bone and cartilage transplants their use and behaviour

Biodegradable polymers in chondrogenesis of human articular chondrocytes

The aim of this study was to evaluate the potential role of polyglycolic acid (PGA), poly(glycolic acid-epsilon-caprolactone) (PGCL), poly(L-lactic acid-glycolic acid) (PLGA), poly(L-lactic acid-epsilon-caprolactone, 75:25 (w/w)) [P(LA-CL)25], poly-epsilon-caprolactone (tetrabutoxy titanium) [PCL(Ti)], and fullerene C-60 dimalonic acid (DMA) in cartilage transplants. After 4 weeks of culture of human articular cartilage, the levels of cell proliferation and differentiation and the expression of cartilage-specific matrix genes were estimated. The relationship between cell differentiation and gap junction protein connexin 43 (Cx43) was also evaluated. All materials except PCL(Ti) retained cell proliferation activities similar to the controls. Cell differentiation levels from the highest to the lowest were in the following order: PGA >> PLGA > PGCL > Control = DMSO > P(LA-CL)25 = PCL(Ti) >> fullerene C-60 DMA. Expression of the collagen type II gene was selectively upregulated for PGA, PGCL, and PLGA and slightly increased for P(LA-CL)25 polymers but was downregulated for fullerene C-60 DMA. Aggrecan gene expression was strongest with PGA and was consistently expressed with other matrices, especially with PGCL and PLGA. However, the expression patterns of the connexin 43 gene were different from the former two genes. Multiple regression analysis revealed a high correlation between cartilage proteoglycans production and expression levels of these three genes.

Alternatives to Patellofemoral Arthroplasty

When surgical intervention becomes necessary in the treatment of a patient with isolated patellofemoral arthritis, the primary alternatives to arthroplasty are tubercle anteriorization or anteromedialization, patellectomy, and cartilage transplantation. The relative merits of these options should be discussed with each patient. There must be healthy central and proximal patella cartilage in order to expect a good result from a tibial tubercle anteriorization. Patellectomy leaves a well-defined functional deficit and therefore is better to avoid whenever possible, although relief of pain after patellectomy can be substantial. Cartilage resurfacing of the trochlea is an attractive alternative. Combining a resurfacing procedure with decompression of the joint by anteromedial or anterior tibial tubercle transfer should help protect the resurfaced area. Replacement of the patellofemoral joint, properly done on a well aligned extensor mechanism, is most attractive when both patella and trochlea are deficient or when an alternative procedure is unacceptable.

Patellofemoral Arthroplasty: The Third Compartment

Isolated arthritis on the patellofemoral articulation has received minimal attention in the past. It is now recognized to be relatively common, especially in women. Treatment alternatives such as patellectomy, unloading osteotomies, debridement, and cartilage transplant have not offered long-term sustainable benefits. Therefore, there is a need for a reliable patellofemoral arthroplasty. The current indications for surgery include middle-aged patients with isolated patellofemoral arthritis without severe maltracking, inflammatory arthritis, crystalline arthropathy, femorotibial arthritis, or high demands. Reports show 60% to 80% good-to-excellent results in the short term and midterm. The main problems with patellofemoral arthroplasty have been patellar instability and patellar edge loading on the condylar cartilage in flexion. Newer designs are addressing both issues and are leading to improved results.

Knorpelzelltransplantation — eine Alternative zur Endoprothese?

The incidence of cartilage lesions is high. Due to pain and loss of function, long-term therapy is often necessary. Isolated, full-thickness articular cartilage lesions with a diameter of 4 cm2 are indications for chondrocyte transplantation. Many outcome studies report good long-term results. In recent years, the cultivation of chondrocytes has changed. Histologic investigations show hyalin-like cartilage after transplantation. Large cartilage lesions facing each other are a therapeutic dilemma in young patients. Implanting unicondylar or bicondylar prostheses is sometimes the last resort for these patients, and there are several reports of good clinical outcome. Cartilage transplantation has until now been recommended for patients younger than 50. It is not an alternative to joint replacement.

Autologous chondrocyte implantation at the knee using a bilayer collagen membrane with bone graft

Autologous chondrocyte implantation (ACI) is a technique used for the treatment of symptomatic osteochondral defects of the knee. A variation of the original periosteum membrane technique is the matrix-induced autologous chondrocyte implantation (MACI) technique. The MACI membrane consists of a porcine type-I/III collagen bilayer seeded with chondrocytes. Osteochondral defects deeper than 8 to 10 mm usually require bone grafting either before or at the time of transplantation of cartilage. We have used a variation of Peterson's ACI-periosteum sandwich technique using two MACI membranes with bone graft which avoids periosteal harvesting. The procedure is suture-free and requires less operating time and surgical exposure. We performed this MACI-sandwich technique on eight patients, five of whom were assessed at six months and one year post-operatively using the modified Cincinnati knee, the Stanmore functional rating and the visual analogue pain scores. All patients improved within six months with further improvement at one year. The clinical outcome was good or excellent in four after six months and one year. No significant graft-associated complications were observed. Our early results of the MACI-sandwich technique are encouraging although larger medium-term studies are required before there is widespread adoption of the technique.

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.

Creating artificial perichondrium by polymer complex membrane macroencapsulation: immune protection and stabilization of subcutaneously transplanted tissue-engineered cartilage

Functional organ or tissue failure is one of the most frequent, devastating and costly problems in modern health care. The field of tissue engineering has tremendous potential for developing new functional tissue. In reconstructive surgery, cartilage engineering could be a serious alternative to the established method of autologous cartilage transplantation. Recent studies demonstrate cartilage engineering by subcutaneous implantation of chondrocyte-seeded PGA/PLA-fibrin glue scaffolds in the backs of nude mice. In both autologous cartilage transplantation and cartilage engineering, the host immune response affects transplant integrity and cartilage morphology to an unforeseeable extent. To investigate whether polyelectrolyte complex (PEC) membranes can prevent rejection of cartilage transplants without neglecting tissue metabolism, tissue-engineered cartilage encapsulated with a PEC membrane was subcutaneously implanted in the backs of nude mice. Non-encapsulated tissue-engineered cartilage was used for the control group. Histochemistry and scanning electron microscopy were performed 4 and 12 weeks after implantation. There was no interaction between the host and the implant with an intact PEC membrane. With protection by PEC encapsulation, implanted tissue-engineered cartilage showed no signs of degeneration and had a significantly weaker cellular immune response than without it. Thus, PEC membrane encapsulation appears to be a novel approach for protecting cartilage implants from host immune response after autologous transplantation.

Aktueller Stand der Behandlungsm�glichkeiten von Knorpeldefekten

Even centuries ago, before much was known about the cell biology of cartilage, it was clear that trauma and degenerative disease affecting cartilage were not easily amenable to treatment. As neither operative nor conservative methods have so far been able to initiate the regeneration of cartilage, the methods used have been aimed at reducing mechanical stress on the damaged tissue or stimulating the overgrowth of defects by fibrous tissue . These efforts have never resulted in the restoration of a normal joint surface. Based on recent successful research in cell biology, many studies have now documented considerable progress in the transplantation of chondrocytes grown in vitro. Another boost for the transplantation of joint cartilage together with bony tissue came with the development of new surgical instruments. In particular, the extremely high-precision methods used in production of the new diamond-coated cutting instruments has made it possible to apply a press-fit technique allowing really accurate defect coverage. Nonetheless, the literature does not contain any classification of the different techniques by indication; nor is any such classification reflected in clinical practice.

Mini-Pig Fresh Osteochondral Allografts Deteriorate after 1 Week of Cold Storage

As a well-defined animal transplantation model, the mini-pig potentially is well-suited for large animal studies of fresh osteochondral allograft transplantation. This study was done to determine the histologic characteristics and function of proteoglycan synthesis of mini-pig articular cartilage after refrigeration in basal media for as much as 6 weeks. Osteochondral sections of 10 mini-pig knees were refrigerated in various media at 4 degrees C for 1 to 42 days after slaughter. Four hundred twenty samples were evaluated by 35S uptake and 260 samples by histologic evaluations. Proteoglycan synthesis declined by 7 days to 21% of the level measured on Day 1 and was undetectable at 42 days. Histologic evaluation revealed progressive degeneration. Mankin scores rose from 3.69 +/- 0.27 on Day 1 to 6.40 +/- 0.18 on Day 7, and logarithmically increased to 10.83 +/- 0.07 on Day 42. These results indicate that the metabolic characteristics of porcine articular cartilage were not retained after refrigeration in basal media for 7 days. Optimum cold storage of porcine osteochondral allografts for cartilage transplantation research may be less than 7 days. Because osteochondral grafts for clinical use currently are stored for greater than 7 days, similar studies of the viability of human articular cartilage are needed.