Objectives. Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations. Methods. Tendon, synovium, and cartilage obtained from routine orthopaedic surgeries were used for ex vivo and in vitro studies using various concentrations of TXA. The in vitro effect of TXA on primary cultured tenocytes, fibroblast-like synoviocytes, and chondrocytes was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays, fluorescent microscopy, and multi-protein apoptotic arrays for cell death. Results. There was a significant (p < 0.01) increase in cell death within all tissue explants treated with 100 mg/ml TXA. MTT assays revealed a significant (p < 0.05) decrease in cell viability in all tissues following treatment with 50 mg/ml or 100 mg/ml of TXA within four hours. There was a significant (p < 0.05) increase in cell apoptosis after one hour of exposure to TXA (100 mg/ml) in all tissues. Conclusion. The current study demonstrates that TXA caused significant periarticular tissue toxicity ex vivo and in vitro at commonly used clinical concentrations. Cite this article: M. McLean, K. McCall, I. D. M. Smith, M. Blyth, S. M. Kitson, L. A. N. Crowe, W. J. Leach, B. P. Rooney, S. J. Spencer, M. Mullen, J. L. Campton, I. B. McInnes, M. Akbar, N. L. Millar. Tranexamic acid toxicity in human periarticular tissues. Bone Joint Res 2019;8:11–18. DOI: 10.1302/2046-3758.81.BJR-2018-0181.R1

1. The hypothesis is put forward that the cartilage of a developing epiphysis consists of two separate moieties. There is a superficial zone which from the first is destined to become articular cartilage and is incapable of ossification, whereas the deeper layers are concerned with the actual growth of the epiphysis and will eventually be converted totally to bone. 2. The results of an experiment which support this theory are described. A piece of developing joint cartilage was excised and replaced in its bed upside down. It was found that although the cartilage continued to proliferate at its normal rate, ossification of the original articular layer did not occur, so that there was a considerable increase in the thickness of the excised cartilage. 3. The supporting evidence for the hypothesis is discussed

Unlike hyaline cartilage, mandibular condylar cartilage can respond to injury by complete healing. We have used the reparative potential of mandibular cartilage to promote repair of defects in a hyaline cartilage joint surface. In 12 adult marmosets, articular fibrocartilage from the mandibular condyles was transplanted into full-thickness defects created in the femoral condyles. Additional defects acted as an ungrafted control group. The grafted defects showed good incorporation of the transplant with restoration of the articular surface within six months. Repair was by proliferation of the fibrocartilaginous graft and chondrogenesis of hyaline cartilage. The repopulating cells were distributed in a matrix of maturing collagen and sulphated glycosaminoglycans. Ungrafted control defects were only partly repaired with fibrous tissue, leaving articular deficiencies. We conclude that transplanted mandibular fibrocartilage can promote reconstitution of wounded hyaline cartilage joint surfaces in primates

The aim of this study was to evaluate the cultivation potential of cartilage taken from the debrided edge of a chronic lesion of the articular surface. A total of 14 patients underwent arthroscopy of the knee for a chronic lesion on the femoral condyles or trochlea. In addition to the routine cartilage biopsy, a second biopsy of cartilage was taken from the edge of the lesion. The cells isolated from both sources underwent parallel cultivation as monolayer and three-dimensional (3D) alginate culture. The cell yield, viability, capacity for proliferation, morphology and the expressions of typical cartilage genes (collagen I, COL1; collagen II, COL2; aggrecan, AGR; and versican, VER) were assessed. The cartilage differentiation indices (COL2/COL1, AGR/VER) were calculated. The control biopsies revealed a higher mean cell yield (1346 cells/mg vs 341 cells/mg), but similar cell proliferation, viability and morphology compared with the cells from the edge of the lesion. The cartilage differentiation indices were superior in control cells: COL2/COL1 (threefold in biopsies (non-significant)); sixfold in monolayer cultures (p = 0.012), and 7.5-fold in hydrogels (non-significant), AGR/VER (sevenfold in biopsies (p = 0.04), threefold (p = 0.003) in primary cultures and 3.5-fold in hydrogels (non-significant)). Our results suggest that the cultivation of chondrocytes solely from the edges of the lesion cannot be recommended for use in autologous chondrocyte implantation

Aims. To investigate the risk factors for progression of articular cartilage damage after anatomical anterior cruciate ligament (ACL) reconstruction. Patients and Methods. A total of 174 patients who underwent second-look arthroscopic evaluation after anatomical ACL reconstruction were enrolled in this study. The graded condition of the articular cartilage at the time of ACL reconstruction was compared with that at second-look arthroscopy. Age, gender, body mass index (BMI), ACL reconstruction technique, meniscal conditions, and other variables were assessed by regression analysis as risk factors for progression of damage to the articular cartilage. Results. In the medial compartment, multivariable logistic regression analysis indicated that partial medial meniscectomy (odds ratio (OR) 6.82, 95% confidence interval (CI) 2.11 to 22.04, p = 0.001), pivot-shift test grade at the final follow-up (OR 3.53, CI 1.39 to 8.96, p = 0.008), BMI (OR 1.15, CI 1.03 to 1.28, p = 0.015) and medial meniscal repair (OR 3.19, CI 1.24 to 8.21, p = 0.016) were significant risk factors for progression of cartilage damage. In the lateral compartment, partial lateral meniscectomy (OR 10.94, CI 4.14 to 28.92, p < 0.001) and side-to-side differences in anterior knee laxity at follow-up (OR 0.63, p = 0.001) were significant risk factors. Conclusion. Partial meniscectomy was found to be strongly associated with the progression of articular cartilage damage despite r anatomical ACL reconstruction. Cite this article: Bone Joint J 2018;100-B:285–93

Osteonecrosis of the femoral head can be caused by a variety of disorders and affects the relatively young patient. Most studies have concentrated on the femoral changes; the sites of early lesions of the labrum and acetabular cartilage have not been recorded. We studied 17 hips with osteonecrosis and a wide congruent joint space on radiographs and by direct inspection of the femoral head, labrum and acetabular cartilage during surgery. All of the femoral heads had some anterosuperior flattening which reduced the head-neck ratio in this area. A consistent pattern of damage to the labrum and the acetabular cartilage was seen in all hips. Intraoperatively, impingement and the cam-effect with its spatial correlation with lesions of the labrum and acetabular cartilage were observed. These findings could be helpful when undertaking conservative surgery for osteonecrosis, since the recognition of early radiologically undetectable acetabular lesions may require modification of the surgical technique

Four patients with injuries of the acetabular triradiate cartilage are presented. In three of them premature fusion of the cartilage occurred; two of these developed acetabular deformity and subluxation of the hip. In all patients the sacroiliac joint also was injured; in two, the joint was completely disrupted, leading to fusion and growth disturbance of the ilium. As injury of the triradiate cartilage is easily missed on the initial radiograph, it is advised that all patients with pelvic trauma should be followed clinically and radiographically for at least one year

The present investigation has shown that crude papain can be used to produce rapid changes in the epiphysial cartilage of various young laboratory animals (rabbits, mice, rats, guinea pigs and cats). 1. Single injections of crude papain produce profound changes in the epiphysial cartilage. These changes disappear within a few days. They are radiographically visible as a narrowing of the epiphysial plates. Histologically, the formation of bony trabeculae in the primary spongiosa is found to be arrested. 2. Repeated injections of crude papain cause permanent damage to the epiphysial cartilage, often with bony closure. Consequently, the longitudinal growth of the injected animals, when compared to the controls, is found to be retarded or permanently arrested, and there may be severe bony deformity. 3. Using inactivated crystalline papain, we have been able to produce changes in the epiphysial cartilage identical with those caused by the injection of crude papain. 4. The injection of crude papain is dispelled by the addition of cysteine, but retains its full strength if hydrogen peroxide is added

Aims

Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2^-/-) display accelerated bone growth.

Microfracture is frequently used as the first line of treatment for the repair of traumatic cartilage defects. We present the clinical and histological results 18 months to two-years after treatment in a 26-year-old male with a post-traumatic chondral defect of the medial femoral condyle managed by microfracture covered with chondrotissue, a cell-free cartilage implant made of a resorbable polyglycolic acid felt and hyaluronic acid

Wear of high-density polyethylene on bone and cartilage has resulted in a large volume of plastic particles being shed into the two knees and two hips studied. The giant-cell foreign-body reaction of the synovium may not be sufficient to cope with the amount of debris presented and the destruction of the endosteal bone in one hip, caused by the wear particles and movement of the prosthesis, has made revision impossible. Articulation of high-density polyethylene against bone or cartilage either by design or by the failure of alignment of the component must be avoided

Continuous strontium administration first induces typical "rickets" in young rats receiving adequate calcium phosphorus and vitamin D but later the widened cartilage spontaneously calcifies intermittently leaving transverse bands consisting largely of osteoid tissue in the metaphysis; in addition to intermittent calcification bone changes indicate that skeletal growth is not uniformly progressive. Subsequently areas of the epiphysial cartilage fail to calcify and localised defects develop; among these are wedge-shaped metaphysial osteoid tissue masses, "invagination" of the epiphysial plate to form multiple nodules of cartilage with proliferating cells in the middle and hypertrophic ones at the periphery, perforation and fragmentation of the epiphysial plate with formation of large cartilage nodules. Multiple cartilage nodules of different sizes appear in the epiphysis, metaphysis and bone shaft. Most bone margins are lined by osteoid seams which only slowly calcify and concomitantly resorption is decreased so that the rate of remodelling of the skeleton is diminished. This type of process may help to explain the results of treatment of osteoporosis by strontium administration

A total of 47 non-walking patients (52 hips) with severe cerebral palsy and with a mean age of 14 years, (9 to 27) underwent a Dega-type pelvic osteotomy after closure of the triradiate cartilage, together with a derotation varus-shortening femoral osteotomy and soft-tissue correction for hip displacement which caused pain and/or difficulties in sitting. The mean follow-up was 48 months (12 to 153). The migration percentage improved from a pre-operative mean of 70% (26% to 100%) to 10% (0% to 100%) post-operatively. In five hips the post-operative migration percentage was greater than 25%, which was associated with continuing pain in two patients. Three patients had persistent hip pain and a migration percentage less than 25%. In five hips a fracture through the acetabulum occurred, and in another there was avascular necrosis of the superior acetabular segment, but these had no adverse effect on functional outcome. We conclude that it is possible to perform a satisfactory pelvic osteotomy of this type in these patients after the triradiate cartilage has been closed

We describe the outcome at a mean follow-up of 8.75 years (7.6 to 9.8) of seven patients who had undergone osteochondral autologous transplantation for full-thickness cartilage defects of the shoulder between 1998 and 2000. These patients have been described previously at a mean of 32.6 months when eight were included. One patient has been lost to follow-up. The outcome was assessed by the Constant shoulder score and the Lysholm knee score to assess any donor-site morbidity. Standard radiographs and MR scores were obtained and compared with the pre-operative findings and the results from the previous review. No patient required any further surgery on the shoulder. The mean Constant score improved significantly until the final follow-up (p = 0.018). The Lysholm score remained excellent throughout. There was a significant progression of osteoarthritic changes from the initial surgery to the first and final follow-up but this did not appear to be related to the size of the defect, the number of cylinders required or the Constant score (p = 0.016). MRI showed that all except one patient had a congruent joint surface at the defect with full bony integration of all osteochondral cylinders. The results have remained satisfactory over a longer period with very good objective and subjective findings

1 . Implants of heterogenous cartilage are known to excite a foreign body reaction in host tissues. In these experiments the way such implants hinder the spread of ossification across a fracture gap was studied. A segment of bone and periosteum was excised from both fibulae in twelve young grivet monkeys, and epiphysial cartilage from a four-day- old rat was implanted in the gap on the left side. The repair processes were investigated at intervals up to twenty-eight weeks. 2. On both sides the gaps were filled by fibrous tissue growing in from the adjacent muscle, and four weeks elapsed before callus started to form. Thereafter ossification across the gap was active on the right side, with bony union in seven or eight weeks. 3. On the left side the implant was slowly resorbed by macrophages and giant cells. Ossification made little headway in the gap after the seventh week. Remains of the implant were found up to the end of the period covered by the experiment. The ends of the fragments were united by fibrous tissue. 4. The fifth to the eighth week seemed to be a critical period, during which the implant and its surrounding inflammatory cells hindered chondrification and ossification and prevented fusion of the masses of callus at the ends of the fragments. 5. It is concluded that anything that impedes callus formation across the fracture line during this critical period may lead to non-union

1. Fifty knees affected by rheumatoid arthritis were studied in detail at synovectomy. 2. The destructive lesions found were relatively constant and are described in detail. 3. Cartilage lesions were much more common than was expected radiologically. 4. The pattern described suggests that articular cartilage is destroyed by contact with diseased synovial membrane but protected by contact with another cartilaginous surface

A case of early closure of the triradiate cartilage, probably secondary to neonatal septic arthritis of the right hip, is reported. Tomograms of the hip showed the triradiate cartilage closed posteriorly, with the anterior portion still open. These findings were confirmed at operation. An arthrogram and a CT scan of the right hip showed subluxation of the femoral head. This unique complication, after an episode of septic arthritis of the hip, has not before been reported in the literature

Biochemical changes in the articular cartilage of the knees of mature dogs, one with natural and four with surgically induced osteoarthritis, have been investigated. The four dogs were killed three, six, nine and forty-eight weeks after division of the right anterior cruciate ligament, the left knees serving as controls. The cartilage of the joints operated on was thicker and more hydrated than the control cartilage; the proteoglycans were more easily extracted and had higher galactosamine/glucosamine molar ratios. The proportion of proteoglycans firmly associated with collagen, and hence not extractable, diminished before fibrillation was demonstrable by indian ink staining of the surface. These biochemical changes were present throughout the entire cartilage of the joints operated on of the dogs killed more than three weeks later, and of the dog with natural osteoarthritis. The results suggest that in response to altered mechanical stresses the chondrocytes synthesise proteoglycans that contain more chondroitin sulphate relative to keratin sulphate than normally, as in immature articular cartilage

We obtained specimens of growth-plate cartilage from four patients with osteogenesis imperfecta. Light microscopy showed structural changes in the tissue and morphological changes in chondrocytes and matrix, particularly in the hypertrophic zone. There were changes in the process of calcification in the primary mineralisation zone of the cartilage. We also found histochemical changes in the matrix glycosaminoglycans (GAGs) in the zones where physiological mineralisation was disturbed and where the trabeculae were interrupted and poorly mineralised. In addition to the known molecular defects in collagen, changes in GAGs and non-collagenous proteins are important factors in the pathogenesis of the disease