We studied the mechanical properties of cartilage from the apparently unaffected compartment of knees with unicompartmental osteoarthritis (OA). Plugs of cartilage and subchondral bone, 8 mm in diameter, were obtained from the tibial plateau of seven patients treated by total knee replacement. Control specimens were obtained from eight cadaver knees of similar age. Specimens were loaded by a plane-ended indentor in a hydraulic materials testing machine; we measured thickness, 'softness', rate of creep, and compressive strength of the articular cartilage. We found that the 'unaffected' cartilage from OA knees was significantly thinner and softer than control cartilage, and it was slightly, although not significantly, weaker. We conclude that the apparently unaffected cartilage in knees with unicompartmental OA is mechanically inferior to normal cartilage, even although clinically, radiologically and morphologically it appears to be sound

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 mm. 2. 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

Lesions within the articular cartilage layer of synovial joints do not heal spontaneously. Some repair cells may appear, but their failure to become established may be related to problems of adhesion to proteoglycan-rich surfaces. We therefore investigated whether controlled enzymatic degradation of surface proteoglycan molecules to a depth of about 1 μm, using chondroitinase ABC, would improve coverage by repair cells. We created superficial lesions (1.0 × 0.2 × 5 mm) in the articular cartilage of mature rabbit knees and treated the surfaces with 1 U/ml of chondroitinase ABC for four minutes. The defects were studied by histomorphometry and electron microscopy at one, three and six months. At one month, untreated lesions were covered to a mean extent of 28% by repair cells; this was enhanced to a mean of 53% after enzyme treatment. By three months, the mean coverage of both control and chondroitinase-ABC-treated defects had diminished dramatically to 0.2% and 13%, respectively, but at six months both untreated and treated lesions had a similar coverage of about 30%, not significantly different from that achieved in untreated knees at one month. These findings suggest that, with time, chondrocytes near the surface of the defect may compensate for the loss of proteoglycans produced by enzyme treatment, thereby restoring the inhibitory properties of the matrix as regards cell adhesion. This supposition was confirmed by electron microscopy. Our results have an important bearing on attempts made to induce healing responses by transplanting chondrogenic cells or by applying growth factors

Rat patellae were preincubated with culture medium M199 for one hour and then with either fresh culture medium or Ringer's solution, Ringer lactate, Ringer glucose, normal saline or Betadine for another hour. The rate of proteoglycan synthesis in the articular cartilage was then measured by uptake of 35SO4 for the next 16 hours. Cartilage metabolism was inhibited by all of the solutions even after a recovery time of 16 hours. The inhibition was by 5% for Ringer's solution, 10% for Ringer glucose (p < 0.01), 20% for saline and Ringer lactate (p < 0.001) and 55% for Betadine (p < 0.001). Ringer's solution is therefore the best choice for joint irrigation during arthroscopy or other procedures

Between 1989 and 1993 we implanted a matrix support prosthesis made of carbon fibre for the treatment of chronic painful articular defects of the patella in 27 patients. The mean period of follow-up was 33 months (11 to 54) with clinical and arthroscopic evaluation of the implant. Overall, there were four excellent, three good, seven fair and 13 poor results. Nine patients subsequently had a patellectomy for persistent pain at a mean of 27 months after surgery (14 to 47). The mean visual analogue pain scores in those who retained their patella were 7.6 before operation and 5.5 at the time of the latest follow-up. Patient satisfaction for the entire group was 41%. There appeared to be good incorporation of the prosthesis and a satisfactory ingrowth of fibrocartilage, but the poor results in 48% and low patient satisfaction discourage us from recommending the procedure for lesions of the articular cartilage of the patella. The consistent seeding of the joint with carbon-fibre debris and a histiocytic giant-cell reaction in the synovium are also a cause for concern

1. In rabbit knees the effects of daily injections of saline, Varidase, blood, blood and Varidase simultaneously, and blood alternating with Varidase every third day have been compared. 2. Saline alone produces changes in joint cartilage comparable with a slight damage to the gel structure of the intercellular matrix. 3. The other four experiments resulted in changes in the articular cartilage comparable with the effects of a partial chemical degradation of the polysaccharide of the intercellular matrix. 4. Blood also induced hypertrophy of the synovial tissues. After the end of the injections healing of the cartilage was slower than with saline or with Varidase. 5. When blood and Varidase were given together the immediate effects were additive, but there was a considerable delay in healing

1. The fibrillar networks of adult human articular cartilage, taken from femoral and acetabular specimens, have been systematically examined by scanning electron microscopy. The internal structures revealed by rupturing the tissue were compared with published findings from transmission electron microscope studies. 2. Though this technique demonstrated the internal fibrillar appearance of cartilage to a remarkable degree, it had several attendant limitations. On final drying, specimens generally exhibited shrinkage which varied within wide limits; this could have altered the internal architecture to some extent. In addition, the rupturing technique, which at the time of this investigation was the only satisfactory method of revealing the fibrillar cartilage structure, may well have had a great influence on the fibril orientations. 3. The fibrils revealed no characteristic collagen periodicity and were considerably thicker than those observed by transmission electron microscopy. It is suggested that a coating of mucin on the collagen fibrils might account for this. 4. At low magnifications the torn layers in the fractured surfaces extended radially from the calcified zone and turned obliquely at or near the articular surface to merge with the distinctly layered superficial zone, thus forming arcade-like structures. That these were not artefacts produced by the fracturing technique was shown by their similarity to the classical arcade pattern of light microscopy. However, the factor which governed the direction of these planes of weakness, be it collagen, mucopolysaccharides or cells, could not be satisfactorily determined. 5. At higher magnifications only three regions of distinct fibrillar organisation could be identified: 1) a surface layer consisting of a random fibrillar network; 2) a superficial zone composed of layers of fibrillar network, intersecting and overlapping in planes parallel to the surface; and 3) elsewhere below the superficial zone a network of virtually random fibrils which extended to the calcified region with apparently little variation in thickness or density. There was little variation from this pattern even in aged fibrillated specimens. 6. At the lower magnification range the scanning electron microscope has revealed the arcade pattern described by light microscopy, while at the higher magnifications the fibrillar organisation as seen by scanning electron microscopy correlated well with the concepts developed by transmission electron microscopy, that is, a random network of fibrils overlaid at the articular surface by a membrane-like system of bundled fibrils. 7. A possible role in the transmission of joint forces is outlined for the above fibrillar organisation

1. Serial slices of articular cartilage obtained at necropsy from apparently normal femoral condyles of individuals between the ages of twenty-six and sixty were examined chemically, by electron microscopy and for permeability. 2. The most superficial layer was shown by chemical analysis and electron microscopy to have the highest collagen content, which fell sharply with distance from the articular surface. On the other hand the glycosaminoglycan content was very low in the superficial layers but increased with depth. This variation was found in all specimens tested but the absolute levels of collagen and of glycosaminoglycans were widely different. There was no correlation of chemical composition with age. 3. Collagen fibrils in the superficial layer were of much smaller diameter than in the deeper zones. 4. Hydraulic permeability was shown to depend more on glycosaminoglycan than on collagen content, although it varied inversely with both these factors. 5. The results obtained demonstrate clearly the close relation between the physical properties of cartilage and its chemical composition

We studied the mechanical and biochemical properties of articular cartilage from 22 osteoarthritic femoral heads obtained at operation and 97 femoral heads obtained at autopsy. Cartilage from the zenith and from the antero-inferior aspect of each head was tested both in tension and in compression. Water content, swelling ability and proteoglycan content were measured, the cartilage was examined histologically and the density of the underlying bone was assessed. Fifty-five of the autopsy specimens were defined as macroscopically normal because they exhibited no progressive fibrillation patterns on staining with Indian ink; but significant changes in water content, bone density and tensile strength related to age were seen in this group. In 20 pairs of femoral heads which were both macroscopically normal, we found, surprisingly, that cartilage from the left and right sides of the same patient was sometimes very different. Compared with the normal autopsy specimens the osteoarthritic specimens had a significantly increased swelling ability, a lower proteoglycan content and impaired mechanical properties, being both weaker in tension and softer in compression. Abnormal autopsy specimens had values intermediate between those of osteoarthritic and normal groups. Results from this abnormal group suggest that there is no primary loss of proteoglycan in early osteoarthritis

Experimental injuries of cartilage and bone were produced by applying shear force to the articular surfaces of the lateral femoral condyles of six-month-old pigs under various loading conditions. The lesions were divided into two groups, 'open' or 'closed', depending on the presence of a crack on the articular surface. Each was further divided into four types according to the depth of penetrating injury: (1) splitting of uncalcified cartilage; (2) splitting at the subchondral plate; (3) subchondral fracture; and (4) intra-articular fracture. When shear force was applied at high speed but with low energy, the articular cartilage surface was the first to crack. At low speed and low energy, splits occurred in the deeper layers first. As the energy increased, both loading conditions eventually resulted in similar open lesions. Experimentally produced shear injuries are useful models for clinical osteochondral fracture, osteochondritis dissecans, and chondromalacia patellae

Articular cartilage from the femoral heads of 27 patients having an arthroplasty for subcapital fracture was studied, and its mechanical and chemical properties compared to those of a group of 33 age-matched macroscopically normal autopsy specimens. Water and proteoglycan contents were measured, as were swelling ability, compressive and tensile strength of the cartilage, and the density of the underlying bone. Cartilage from the fracture specimens had a significantly reduced proteoglycan content, as measured by fixed charge density, and increased swelling ability. These results indicate that this group differs from the "normal" population and care should be taken before they are accepted as control material for studies on osteoarthritic cartilage. Another finding was that bone density was much the same in the fracture and the normal group. This casts some doubt upon the concept that patients who sustain subcapital fractures are more osteoporotic than the average for the same age range

We describe a method which may be useful for the selection of samples for the study of early fibrillation in human articular cartilage. Blocks of cartilage and bone were cut post-mortem from the medial tibial condyles of 29 male and 31 female subjects and the grade of fibrillation was assessed from sections. Contiguous, unfixed blocks of cartilage from the same surface were immersed in a solution of the dye Light Green SF. Sections of these blocks were cut and the rate of penetration of the dye measured at 30 equidistant points across the condylar surface. The relationship between the grade of fibrillation and the rate of dye diffusion was then determined. We demonstrated a significant correlation between the two variables. This technique may make it possible to detect a pre-fibrillary state in apparently normal specimens

1. We have shown that the permeability of cartilage is the same in necropsy specimens as in the living animal. We have concluded that studies of material transport into cartilage carried out on necropsy specimens validly reflect in vivo conditions.

2. We have studied the effect of agitation of the fluid in which cartilage is immersed upon the rate of diffusion of substances into cartilage and have found that agitation increases the rate of penetration up to three or four fold. We believe that it may be inferred from this fact that the nutrition of cartilage is partly dependent on joint movement.

3. We have examined the permeability of the bone-cartilage interface to water and solutes and have found that in the adult no detectable material transfer occurs across this zone. In the child on the other hand the bone-cartilage interface appears to be permeable to water and solutes.

4. We have measured the diffusion coefficient of glucose in cartilage and have hence estimated the depth of cartilage which can be adequately supplied with glucose from the synovial fluid in the presence and absence of agitation.

5. We have examined both experimentally and theoretically the possible effect of intermittent loading on the rate of penetration of substances into cartilage. We have concluded that at low pressures intermittent loading contributes little to the material transfer into cartilage. At high pressures intermittent loading does lead to the transport of solutes into cartilage but it cannot significantly increase the rate of transfer above that attributable to normal diffusion. Loading cartilage surfaces for prolonged periods of time without allowing intermittent relaxation would be expected to lead to decreased diffusion, without any absorption of fresh fluid attributable to the action of a pump, and would thus result in an overall decrease in the rate of penetration of substances into cartilage.

Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous ‘chondrocyte-fibrin’ construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis.

All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O’Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage.

Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI.

1. Techniques are described for homografting intact or partly digested hyaline cartilage or isolated chondrocytes on to cancellous bone in rabbits.

2. Material which had been cooled to and thawed from -79 degrees Centigrade either in the presence or absence of the protective substance dimethyl sulphoxide was grafted in the same way. In control experiments samples were boiled before grafting.

3. Necropsies were performed at intervals varying from two to twenty-six weeks later and the graft sites were removed, fixed and decalcified. Paraffin sections were stained histologically.

4. Freshly isolated chondrocytes or chondrocytes which had been frozen in the presence of dimethyl suiphoxide formed new matrix within two weeks and did not succumb to a homograft reaction. By the sixth week they had become aligned in columns surrounded by well stained matrix. There were signs oferosion by invading capillaries and osteoblasts, but no lymphocytes were seen. By the twelfth week invasion by trabeculae of newly formed bone was well advanced and by the twenty-sixth week the grafts were difficult to find although there had been no sign at any stage of an immunological reaction.

5. New matrix was also formed in homografts of hyaline cartilage which had been treated with papain or with papain and collagenase. After freezing in the presence of dimethyl sulphoxide, small areas ofthe grafts seemed to contain living cells which had formed new matrix. Other areas were disintegrating.

6. The homografts of intact cartilage showed a variety of appearances suggesting that the old matrix was gradually leached out and that chondrocytes liberated in vivo formed a new matrix.

7. Intact or partly digested cartilage which had either been frozen without dimethyl suiphoxide or boiled disintegrated and was rapidly replaced by bone after grafting.

8. When specimens of partly digested cartilage or isolated chondrocytes were homografted On to sites denuded of cartilage on the articular surface of the rabbit humeral head, nodules of fresh cartilage were formed. They were embedded in fibrous tissue derived, presumably, from marrow cavities opened up at the time of operation.

Composites of chondrocytes and polymerised fibrin were supplemented with insulin-like growth factor-I (IGF-I) during the arthroscopic repair of full-thickness cartilage defects in a model of extensive loss of cartilage in horses. Repairs facilitated with IGF-I and chondrocyte-fibrin composites, or control defects treated with chondrocyte-fibrin composites alone, were compared before death by the clinical appearance and repeated analysis of synovial fluid, and at termination eight months after surgery by tissue morphology, collagen typing, and biochemical assays. The structure of cartilage was evaluated histologically by Toluidine Blue reaction and collagen type-I and type-II in situ hybridisation and immunohistochemistry. Repair tissue was biochemically evaluated by DNA assay, proteoglycan quantitation and characterisation, assessment of collagen by reverse-phase high-performance liquid chromatography, and collagen typing using cyanogen bromide digestion and peptide separation by polyacrylamide gel electrophoresis.

The results at eight months showed that the addition of IGF-I to chondrocyte grafts enhanced chondrogenesis in cartilage defects, including incorporation into surrounding cartilage. Gross filling of defects was improved, and the tissue contained a higher proportion of cells producing type-II collagen. Measurements of collagen type II showed improved levels in IGF-I-treated defects, supporting in situ hybridisation and immunohistochemical assessments of the defects. IGF-I improves the repair capabilities of chondrocyte-fibrin grafts in large full-thickness repair models.

1. Osmium tetroxide and nitrogen mustard were injected into normal adult rabbit joints. Within one week widespread chondrocyte necrosis had occurred as evidenced by electron microscopic examination and radioactive proline uptake autoradiography.

2. Initially, the cartilage matrix was intact but three to seven months later the cartilage surface began to disintegrate.

3. These studies indicate that osmium tetroxide and nitrogen mustard are unsuitable agents for chemical synovectomy.

4. They also indicate that there may be a long latent period between cartilage cell death and cartilage destruction, and that the evaluation of any agent for chemical synovectomy must take this into consideration.