Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model. The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count. Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model.
Human articular cartilage samples were retrieved from the resected material of patients undergoing total knee replacement. Samples underwent automated controlled freezing at various stages of preparation: as intact articular cartilage discs, as minced articular cartilage, and as chondrocytes immediately after enzymatic isolation from fresh articular cartilage. Cell viability was examined using a LIVE/DEAD assay which provided fluorescent staining. Isolated chondrocytes were then cultured and Alamar blue assay was used for estimation of cell proliferation at days zero, four, seven, 14, 21 and 28 after seeding. The mean percentage viabilities of chondrocytes isolated from group A (fresh, intact articular cartilage disc samples), group B (following cryopreservation and then thawing, after initial isolation from articular cartilage), group C (from minced cryopreserved articular cartilage samples), and group D (from cryopreserved intact articular cartilage disc samples) were 74.7% (95% confidence interval (CI) 73.1 to 76.3), 47.0% (95% CI 43 to 51), 32.0% (95% CI 30.3 to 33.7) and 23.3% (95% CI 22.1 to 24.5), respectively. Isolated chondrocytes from all groups were expanded by the following mean proportions after 28 days of culturing: group A ten times, group B 18 times, group C 106 times, and group D 154 times. This experiment demonstrated that it is possible to isolate viable chondrocytes from cryopreserved intact human articular cartilage which can then be successfully cultured.
We identified 1305 femoral impaction bone grafting revisions using the Exeter stem performed between 1989 and 2002 in 30 hospitals throughout Sweden. There were 1188 patients with a mean age of 71 years (29 to 94) followed up for between five and 18 years. The participating departments reported 70 further revisions in total, of which 57 could also be identified on the Swedish National Arthroplasty Registry. Kaplan-Meier survivorship for all causes of failure was 94.0% (95% confidence interval (CI) 92 to 96) for women and 94.7% (95% CI, 92 to 96) for men at 15 years. Survivorship at 15 years for aseptic loosening was 99.1% (95% CI 98.4 to 99.5), for infection 98.6% (95% CI 97.6 to 99.2), for subsidence 99.0% (95% CI 98.2 to 99.4) and for fracture 98.7% (95% CI 97.9 to 99.2) Statistically significant predictors of failure were the year in which revision was conducted (p <
0.001). The number of previous revisions was slightly above the level of signifance (p = 0.056). Age, gender, the length of the stem and previous septic loosening were not predictors of failure (p = 0.213, p = 0.399, p = 0.337, p = 0.687, respectively). The difference in survivorship between high- and low-volume departments was only 3% at ten years. We conclude that impaction bone grafting with the Exeter stem has an excellent long-term survivorship following revision arthroplasty. The technique of impaction grafting appears to be reliable, can be learned rapidly and produces a predictably low incidence of aseptic loosening.
The haematoma occurring at the site of a fracture is known to play an important role in bone healing. We have recently shown the presence of progenitor cells in human fracture haematoma and demonstrated that they have the capacity for multilineage mesenchymal differentiation. There have been many studies which have shown that low-intensity pulsed ultrasound (LIPUS) stimulates the differentiation of a variety of cells, but none has investigated the effects of LIPUS on cells derived from human fracture tissue including human fracture haematoma-derived progenitor cells (HCs). In this
We describe the surgical technique and results of arthroscopic subtalar release in 17 patients (17 feet) with painful subtalar stiffness following an intra-articular calcaneal fracture of Sanders’ type II or III. The mean duration from injury to arthroscopic release was 11.3 months (6.4 to 36) and the mean follow-up after release was 16.8 months (12 to 25). The patient was positioned laterally and three arthroscopic portals were placed anterolaterally, centrally and posterolaterally. The sinus tarsi and lateral gutter were debrided of fibrous tissue and the posterior talocalcaneal facet was released. In all, six patients were very satisfied, eight were satisfied and three were dissatisfied with their results. The mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score improved from a mean of 49.4 points (35 to 66) pre-operatively to a mean of 79.6 points (51 to 95). All patients reported improvement in movement of the subtalar joint. No complications occurred following operation, but two patients subsequently required subtalar arthrodesis for continuing pain. In the majority of patients a functional improvement in hindfoot function was obtained following arthroscopic release of the subtalar joint for stiffness and pain secondary to Sanders type II and III fractures of the calcaneum.
Surgery is considered to be the most effective treatment for cartilaginous tumours. In recent years, a trend has emerged for patients with low-grade tumours to be treated less invasively using curettage followed by various forms of adjuvant therapy. We investigated the potential for phenol to be used as an adjuvant. Using a human chondrosarcoma-derived cartilage-producing cell line OUMS-27 as an in vitro model we studied the cytotoxic effect of phenol and ethanol. Since ethanol is the standard substance used to rinse phenol out of a bone cavity, we included an assessment of ethanol to see whether this was an important secondary factor with respect to cell death. The latter was assessed by flow cytometry. A cytotoxic effect was found for concentrations of phenol of 1.5% and of ethanol of 42.5%. These results may provide a clinical rationale for the use of both phenol and ethanol as adjuvant therapy after intralesional curettage in low-grade central chondrosarcoma and justify further investigation.
Carbonate-substituted hydroxyapatite (CHA) is more osteoconductive and more resorbable than hydroxyapatite (HA), but the underlying mode of its action is unclear. We hypothesised that increased resorption of the ceramic by osteoclasts might subsequently upregulate osteoblasts by a coupling mechanism, and sought to test this in a large animal model. Defects were created in both the lateral femoral condyles of 12 adult sheep. Six were implanted with CHA granules bilaterally, and six with HA. Six of the animals in each group received the bisphosphonate zoledronate (0.05 mg/kg), which inhibits the function of osteoclasts, intra-operatively. After six weeks bony ingrowth was greater in the CHA implants than in HA, but not in the animals given zoledronate. Functional osteoclasts are necessary for the enhanced osteoconduction seen in CHA compared with HA.
Infection of a total hip replacement (THR) requires component removal and thorough local debridement. Usually, long-term antibiotic treatment in conjunction with a two-stage revision is required. This may take several months. One-stage revision using antibiotic-loaded cement has not gained widespread use, although the clinical and economic advantages are obvious. Allograft bone may be impregnated with high levels of antibiotics, and in revision of infected THR, act as a carrier providing a sustained high local concentration. We performed 37 one-stage revision of infected THRs, without the use of cement. There were three hips which required further revision because of recurrent infection, the remaining 34 hips (92%) stayed free from infection and stable at a mean follow-up of 4.4 years (2 to 8). No adverse effects were identified. Incorporation of bone graft was comparable with unimpregnated grafts. Antibiotic-impregnated allograft bone may enable reconstruction of bone stock, insertion of an uncemented implant and control of infection in a single operation in revision THR for infection.
We investigated whether simultaneous bilateral sequential total hip replacement (THR) would increase the rate of mortality and complications compared with unilateral THR in both low- and high-risk groups of patients. We enrolled 978 patients with bilateral and 1666 with unilateral THR in the study. There were no significant pre-operative differences between the groups in regard to age, gender, body mass index, diagnosis, comorbidity as assessed by the grading of the American Society of Anesthesiologists (ASA), the type of prosthesis and the duration of follow-up. The mean follow-up was for 10.5 years (5 to 13) in the bilateral THR group and 9.8 years (5 to 14) in the unilateral group. The peri-operative mortality rate of patients who had simultaneous bilateral THR (0.31%, three of 978 patients) was similar to that of patients with unilateral THR (0.18%, three of 1666 patients). The peri-operative mortality rate of patients in the bilateral group was similar in high risk and low risk patients (0.70%, two of 285 patients vs 0.14%, one of 693 patients) and this was also true in the unilateral THR group (0.40%, two of 500 patients vs 0.09%, one of 1166 patients). Patients with bilateral THR required more blood transfusions and a longer hospital stay than those in the unilateral THR group. There was no significant difference (p = 0.32) in the overall number of complications between the groups. This was also true for the low-risk (p = 0.81) vs high-risk (p = 0.631) patients. Our findings confirm that simultaneous sequential bilateral THR is a safe option for patients who are considered to be either high or low risk according to the ASA classification.
A comprehensive review of the literature relating to the pathology and management of the diabetic foot is presented. This should provide a guide for the treatment of ulcers, Charcot neuro-arthropathy and fractures involving the foot and ankle in diabetic patients.
The purpose of this study was to determine objectively the outcome of total knee replacement in patients with ankylosed knees. There were 82 patients (99 knees) with ankylosed knees who underwent total knee replacement with a condylar constrained or a posterior stabilised prosthesis. Their mean age was 41.9 years (23 to 60) and the mean follow-up was for 8.9 years (6.6 to 14). Pre- and post-operative data included the Hospital for Special Surgery (HSS), the Knee Society (KS) and the Western Ontario and McMaster University Osteoarthritis index (WOMAC) scores. The mean HSS, KS and WOMAC scores improved from 60, 53, and 79 pre-operatively to 81, 85, and 37 at follow-up. These improvements were statistically significant (p = 0.018, 0.001 and 0.014 respectively). The mean physical, social and emotional WOMAC scores also improved significantly (p = 0.032, p = 0.023 and p <
0.001 respectively). The mean satisfaction score was 8.5 ( Total knee replacement gives good mid-term results in patients with ankylosed knees.
Bleeding is a major complication of revision total hip replacement. We report a case where the inflated balloon of a urinary catheter was used to temporarily control intrapelvic bleeding from the superior gluteal artery, while definitive measures for endovascular embolisation were made.
We describe a near-fatal event, probably due to air embolism, following an air arthrogram for developmental hip dysplasia in a baby aged four months. The sequence of events and the subsequent treatment are described. There is little information about this complication in the literature. The presumed mechanism and alternative methods for confirmation of placement of the needle are discussed. We no longer use air arthrography in children.
Compartment pressures have not previously been studied in healthy children. We compared the pressures in the four lower leg compartments of healthy children with those of healthy adults. We included patients aged between two months and six years, and measured the pressures in 80 compartments of 20 healthy children using simple needle manometry. Measurements were repeated in a control group of 20 healthy adults. The mean compartment pressure in the lower leg in children was significantly higher than in adults (p <
0.001). On average, pressures in the four compartments varied between 13.3 mmHg and 16.6 mmHg in the children and between 5.2 mmHg and 9.7 mmHg in the adults. The latter is in accordance with those recorded in the literature. The mean arterial pressure did not relate to age or to pressure in the compartment. The findings of this study that the normal compartment pressure of the lower leg in healthy children is significantly higher than that in adults may be of considerable significance in clinical decision-making in children of this age.
We examined cultured osteoblasts derived from paired samples from the greater tuberosity and acromion from eight patients with large chronic tears of the rotator cuff. We found that osteoblasts from the tuberosity had no apparent response to mechanical stimulation, whereas those derived from the acromion showed an increase in alkaline phosphatase activity and nitric oxide release which is normally a response of bone cells to mechanical strain. By contrast, we found that cells from both regions were able to respond to dexamethasone, a well-established promoter of osteoblastic differentiation, with the expected increase in alkaline phosphatase activity. Our findings indicate that the failure of repair of the rotator cuff may be due, at least in part, to a compromised capacity for mechanoadaptation within the greater tuberosity. It remains to be seen whether this apparent decrease in the sensitivity of bone cells to mechanical stimulation is the specific consequence of the reduced load-bearing history of the greater tuberosity in these patients.
Successful healing of a nine-year tibial nonunion resistant to six previous surgical procedures was achieved by tissue engineering. We used autologous bone marrow stromal cells (BMSCs) expanded to 5 × 106 cells after three weeks’ tissue culture. Calcium sulphate (CaSO4) in pellet form was combined with these cells at operation. The nonunion was clinically and radiologically healed two months after implantation. This is the description of on healing of a long-standing tibial nonunion by tissue engineering. The successful combination of BMSCs and CaSO4 has not to our knowledge been reported in a clinical setting.
The aim of this study was to define the microcirculation of the normal rotator cuff during arthroscopic surgery and investigate whether it is altered in diseased cuff tissue. Blood flow was measured intra-operatively by laser Doppler flowmetry. We investigated six different zones of each rotator cuff during the arthroscopic examination of 56 consecutive patients undergoing investigation for impingement, cuff tears or instability; there were 336 measurements overall. The mean laser Doppler flowmetry flux was significantly higher at the edges of the tear in torn cuffs (43.1, 95% confidence interval (CI) 37.8 to 48.4) compared with normal cuffs (32.8, 95% CI 27.4 to 38.1; p = 0.0089). It was significantly lower across all anatomical locations in cuffs with impingement (25.4, 95% CI 22.4 to 28.5) compared with normal cuffs (p = 0.0196), and significantly lower in cuffs with impingement compared with torn cuffs (p <
0.0001). Laser Doppler flowmetry analysis of the rotator cuff blood supply indicated a significant difference between the vascularity of the normal and the pathological rotator cuff. We were unable to demonstrate a functional hypoperfusion area or so-called ‘critical zone’ in the normal cuff. The measured flux decreases with advancing impingement, but there is a substantial increase at the edges of rotator cuff tears. This might reflect an attempt at repair.
The gelatin-based haemostyptic compound Spongostan was tested as a three-dimensional (3D) chondrocyte matrix in an in vitro model for autologous chondrocyte transplantation using cells harvested from bovine knees. In a control experiment of monolayer cultures, the proliferation or de-differentiation of bovine chondrocytes was either not or only marginally influenced by the presence of Spongostan (0.3 mg/ml). In monolayers and 3-D Minusheet culture chambers, the cartilage-specific differentiation markers aggrecan and type-II collagen were ubiquitously present in a cell-associated fashion and in the pericellular matrix. The Minusheet cultures usually showed a markedly higher mRNA expression than monolayer cultures irrespective of whether Spongostan had been present or not during culture. Although the de-differentiation marker type-I collagen was also present, the ratio of type-I to type-II collagen or aggrecan to type-I collagen remained higher in Minusheet 3-D cultures than in monolayer cultures irrespective of whether Spongostan had been included in or excluded from the monolayer cultures. The concentration of GAG in Minusheet cultures reached its maximum after 14 days with a mean of 0.83 ± 0.8 μg/106 cells; mean ±, Our results suggest that Spongostan is in principle suitable as a 3-D chondrocyte matrix, as demonstrated in Minusheet chambers, in particular for a culture period of 14 days. Clinically, differentiating effects on chondrocytes, simple handling and optimal formability may render Spongostan an attractive 3-D scaffold for autologous chondrocyte transplantation.
The aim of our study was to investigate the effect of platelet-rich plasma on the proliferation and differentiation of rat bone-marrow cells and to determine an optimal platelet concentration in plasma for osseous tissue engineering. Rat bone-marrow cells embedded in different concentrations of platelet-rich plasma gel were cultured for six days. Their potential for proliferation and osteogenic differentiation was analysed. Using a rat limb-lengthening model, the cultured rat bone-marrow cells with platelet-rich plasma of variable concentrations were transplanted into the distraction gap and the quality of the regenerate bone was evaluated radiologically. Cellular proliferation was enhanced in all the platelet-rich plasma groups in a dose-dependent manner. Although no significant differences in the production and mRNA expression of alkaline phosphatase were detected among these groups, mature bone regenerates were more prevalent in the group with the highest concentration of platelets. Our results indicate that a high platelet concentration in the platelet-rich plasma in combination with osteoblastic cells could accelerate the formation of new bone during limb-lengthening procedures.
An understanding of the remodelling of tendon is crucial for the development of scientific methods of treatment and rehabilitation. This study tested the hypothesis that tendon adapts structurally in response to changes in functional loading. A novel model allowed manipulation of the mechanical environment of the patellar tendon in the presence of normal joint movement via the application of an adjustable external fixator mechanism between the patella and the tibia in sheep, while avoiding exposure of the patellar tendon itself. Stress shielding caused a significant reduction in the structural and material properties of stiffness (79%), ultimate load (69%), energy absorbed (61%), elastic modulus (76%) and ultimate stress (72%) of the tendon compared with controls. Compared with the material properties the structural properties exhibited better recovery after re-stressing with stiffness 97%, ultimate load 92%, energy absorbed 96%, elastic modulus 79% and ultimate stress 80%. The cross-sectional area of the re-stressed tendons was significantly greater than that of stress-shielded tendons. The remodelling phenomena exhibited in this study are consistent with a putative feedback mechanism under strain control. This study provides a basis from which to explore the interactions of tendon remodelling and mechanical environment.