There is an ever-increasing clinical need for the regeneration and replacement of tissue to replace soft tissue lost due to trauma, disease and cosmetic surgery. A potential alternative to the current treatment modalities is the use of tissue engineering applications using mesenchymal stem cells that have been identified in many tissue including the infrapatellar fat pad. In this study, stem cells isolated from the infrapatellar fat pad were characterised to ascertain their origin, and allowed to undergo adipogenic differentiation to confirm multilineage differentiation potential. The infrapatellar fat pad was obtained from total knee replacement for osteoarthritis. Cells were isolated and expanded in monolayer culture. Cells at passage 2 stained strongly for CD13, CD29, CD44, CD90 and CD105 (mesenchymal stem cell markers). The cells stained poorly for LNGFR and STRO1 (markers for freshly isolated bone marrow derived stem cells), and sparsely for 3G5 (pericyte marker). Staining for CD34 (haematopoetic marker) and CD56 (neural and myogenic lineage marker) was negative. For adipogenic differentiation, cells were cultured in adipogenic inducing medium consisting of basic medium with 10ug/ml insulin, 1uM dexamthasone, 100uM indomethacin and 500uM 3-isobutyl-1-methyl xanthine. By day 16, many cells had lipid vacuoles occupying most of the cytoplasm. On gene expression analyses, the cells cultured under adipogenic conditions had almost a 1,000 fold increase in expression of peroxisome proliferator-activated receptor gamma-2 (PPAR gamma-2) and 1,000,000 fold increase in expression of lipoprotein lipase (LPL). Oil red O staining confirmed the adipogenic nature of the observed vacuoles and showed failure of staining in control cells. Our results show that the human infrapatellar fat pad is a viable potential autogeneic source for mesenchymal stem cells capable of adipogenic differentiation as well as previously documented ostegenic and chondrogenic differentiation. This cell source has potential use in tissue engineering applications.
Balancing service provision and surgical training is a challenging issue that affects all healthcare systems. A multicentre prospective study of 1501 total hip replacements was undertaken to investigate whether there is an association between surgical outcome and the grade of the operating surgeon, and whether there is any difference in outcome if surgeons’ assistants assist with the operation, rather than orthopaedic trainees. The primary outcome measure was the change in the Oxford hip score (OHS) at five years. Secondary outcomes included the rate of revision and dislocation, operating time, and length of hospital stay. There was no significant difference in ΔOHS or complication rates between operations undertaken by trainers and trainees, or those at which surgeons’ assistants and trainees were the assistant. However, there was a significant difference in the duration of surgery, with a mean reduction of 28 minutes in those in which a surgeons’ assistant was the assistant. This study provides evidence that total hip replacements can be performed safely and effectively by appropriately trained surgeons in training, and that there are potential benefits of using surgeons’ assistants in orthopaedic surgery.
A prospective, multi-centre study was carried out on 1421 total hip replacements between January 1999 and July 2007 to examine if obesity has an effect on clinical outcomes. The patients were categorised into three groups: non-obese (body mass index (BMI) <
30 kg/m2), obese (BMI 30 to 40 kg/m2) and morbidly obese (BMI >
40 kg/m2). The primary outcome measure was the change in Oxford hip score at five years. Secondary outcome measures included dislocation and revision rates, increased haemorrhage, deep infection, deep-vein thrombosis and pulmonary embolism, mean operating time and length of hospital stay. Radiological analysis assessing heterotopic ossification, femoral osteolysis and femoral stem positioning was performed. Data were incomplete for 362 hips (25.5%) There was no difference in the change in the Oxford hip score, complication rates or radiological changes at five years between the groups. The morbidly obese group was significantly younger and required a significantly longer operating time. Obese and morbidly obese patients have as much to gain from total hip replacement as non-obese patients.
Excessive acetabular cover secondary to a retroverted acetabulum causes pincer impingement, which may cause early osteoarthritis of the hip. Our aim was to determine if there was a relationship between acetabular version and osteoarthritis of the hip. Using image processing and analysis software we studied 117 CT images of the hip in patients aged less than 65 years who had undergone a CT virtual colonoscopy. The mean CT joint space of the 18 hips with acetabular retroversion was narrower compared with the 99 hips with normal acetabular alignment (p <
0.0001). A correlation of r = 0.46 (p <
0.01) was found between right hip acetabular version and the mean right hip joint space and of r = 0.31 (p = 0.02) between left hip acetabular version and the mean left hip joint space. Acetabular retroversion is associated with radiological evidence of osteoarthritis of the hip. An understanding of the mechanical basis of osteoarthritis of the hip allows early treatment of the underlying structural abnormality and prevents progression of the degenerative condition.
Resurfacing total hip replacement using metal on metal bearings is increasing in popularity, but the outcomes are currently unclear. We report a series of 23 hips in 20 patients who underwent resurfacing total hip replacement over a period of 4 years. The mean age at surgery was 47 years (21–61). There were 8 females and 12 male patients. The mean follow up was 27 months (range 6 to 50 months). Before performing this study, our impression was that most outcomes were good but that there appeared to be more variability in pain relief than anticipated after conventional total hip replacement. Most were performed for primary osteoarthritis; other diagnoses included AVN, DDH and multiple epiphyseal dysplasia. Outcomes were measured examining x rays, survival of the implant and the Oxford hip questionnaire. There were no early revisions, but we are aware of one loose acetabular cup (in a patient with DDH) which is asymptomatic but which will probably require revision. There were no femoral neck fractures. The median score using the Oxford hip questionnaire was 15 (mean 23.5; range 12 to 41). These outcomes compare favourably with those reported at 6 months follow up after conventional total hip replacement by the Oxford group (OHQ median score 22; mean 24.3 (12 to 51)). We conclude that resurfacing metal on metal hip replacement gives comparable results to total hip replacement at early follow up. The age of the Oxford groups patients was considerably older than ours (75 years), and a comparative trial of resurfacing versus conventional hip replacements will be required to determine which gives better short and long term results in young patients. There may be more variability in pain relief after resurfacing THR than after conventional THR, but this will require a larger study to determine with confidence.
Aseptic loosening of orthopaedic implants is usually attributed to the action of wear debris from the prosthesis. Recent studies, however, have also implicated physical pressures in the joint as a further cause of loosening. We have examined the role of both wear debris and pressure on the secretion of two chemokines, MIP-1α and MCP-1, together with M-CSF and PGE2, by human macrophages in vitro. The results show that pressure alone stimulated the secretion of more M-CSF and PGE2 when compared with control cultures. Particles alone stimulated the secretion of M-CSF and PGE2, when compared with unstimulated control cultures, but did not stimulate the secretion of the two chemokines. Exposure of macrophages to both stimuli simultaneously had no synergistic effect on the secretion of the chemokines, but both M-CSF and PGE2 were increased in a synergistic manner. Our findings suggest that pressure may be an initiating factor for the recruitment of cells into the periprosthetic tissue.
The best follow up strategy after hip replacement (THR) is unclear. There are conflicting demands to obtain early diagnosis of loosening, and to minimise clinic visits. It would be desirable to achieve follow up with a validated symptom questionnaire alone, but it is unclear how frequently THRs are asymptomatic during early loosening. This study examined the relationship between patient reported symptoms after THR using two measures (Oxford Hip Questionnaire (OHQ) and Visual Analogue Scale (VAS)), and the classification of the patients AP x ray of the hip as having definite loosening, possible loosening, or a sound implant. We examined data from 325 patients who had undergone a standard Charnley THR for osteoarthritis. Patients had a mean follow-up of 85 months (range 24–144). X rays were examined by a single Consultant Orthopaedic surgeon, and classified as satisfactory, possible loosening or definite loosening. As expected, the large majority of patients had a satisfactory appearance on x-ray at all-time points. 12 patients were classified as having definite loosening on the basis of the available x-rays. 8 of these were subsequently listed for revision surgery at review. 20 patients were noted to have evidence of possible loosening. Examination of the Oxford hip questionnaire and VAS data demonstrated a strong relationship between OHQ value and the VAS result for pain (r = 0.78, p <
0.001, Spearman rank correlation). Data were analysed separately (using ROC curves) to determine whether the OHQ or VAS was a satisfactory method of selecting patients who fell into “definite loosening” or “definite or possible loosening” groups. Neither OHQ or VAS were sensitive or specific for definite or possible loosening. We conclude that x rays are required for early detection of loosening, and that follow up by OHQ or VAS alone is insufficient for this purpose.
Aseptic loosening and osteolysis around prosthetic joints are the principal causes of failure and consequent revision. During this process activated macrophages produce cytokines which are thought to promote osteolysis by osteoclasts. Changes in pressure within the space around implants have been proposed as a cause of loosening and osteolysis. We therefore studied the effect of two different regimes of cyclic pressure on the production of interleukin-1β (IL-1β), IL-6 and tumour necrosis factor-α (TNF-α) by cultured human monocyte-derived (M-D) macrophages. There was a wide variation in the expression of cytokines in non-stimulated M-D macrophages from different donors and therefore cells from the same donor were compared under control and pressurised conditions. Both regimes of cyclic pressure were found to increase expression of IL-6 and TNF-α. Expression of IL-1β was increased by a higher-frequency regime only. Our findings suggest that M-D macrophages are activated by cyclic pressure. Further work will be required to understand the relative roles of frequency, amplitude and duration of applied pressure in the cellular effects of cyclic pressure in this system.