Autologous chondrocyte implantation is a NICE approved intervention however it involves the morbidity of two operations, a prolonged rehabilitation and substantial healthcare costs. This study describes a novel, one-step, bone marrow (BM) derived mesenchymal stem cell (MSC) transplantation technique for treating knee osteochondral lesions and presents our prospective clinical study investigating the success of this technique in 206 lesions over a 5 year period. The surgical technique involves harvesting BM from patients’ anterior superior iliac spines, centrifugation to isolate MSCs and seeding into a type 1 collagen scaffold (SyngenitTM Biomatrix). Autologous fibrin glue is used to secure the scaffold into the defect. Inclusion criteria included patients aged 15 – 55 years old with symptomatic osteochondral lesions >1cm2. Exclusion criteria included patients with ligament instability, uncorrected alignment, inflammatory arthropathy and a Body Mass Index >35 kg/m2. Outcome measures included the Modified Cincinnati Knee Rating System (MCKRS), complications and reoperations.Abstract
Background
Methodology
The Royal National Orthopaedic Hospital has completed an extensive trial of ACI versus MACI in the treatment of symptomatic osteochondral defects of the knee. A new technique has now been proposed which is quicker and easier to perform. This is the Gel-Type Autologous Chondrocyte Transplantation, CHONDRONTM. At Stanmore CHONDRON has been used for the past 17 months. Our aim was to assess the short term functional outcome of patients who have undergone CHONDRONTM using validated outcome scoring questionnaires. We retrospectively reviewed the notes of 43 patients that had undergone CHONDRONTM over one year ago and scored them using the Modified Cincinnati Score, the Visual Analogue Score and the Benltey Stanmore Functional Rating Score. The mean pre-operative Modified Cincinnati Score was 39.9, which improved to a mean of 59.8 post-operatively. The mean Visual Analogue Score improved from 6.7 to 5.1 post-operatively. The median Bentley Functional Rating Score was 3 pre-operatively and 2 post-operatively. These early results show that 76% of the patients who were treated with CHONDRONTM experienced a reduction in pain and improvement in post-operative function. In the patients in whom the symptoms were worse, the deterioration in score could be partly explained by numerous previous procedures on the same site, presence of early osteoarthritis or the presence of multiple osteochondral lesions. This highlights the importance of careful patient selection in order to gain maximum benefit from the procedure.RESULTS
CONCLUSIONS
Chondral injuries of the knee are extremely common and present a unique therapeutic challenge due to the poor intrinsic healing of articular cartilage. These injuries can lead to significant functional impairment. There are several treatment modalities for articular osteochondral defects, one of which is autologous chondrocyte implantation. Our study evaluates the mid to long term functional outcomes in a cohort of 828 patients who have undergone an autologous chondrocyte implantation procedure (either ACI or MACI), identifying retrospectively factors that may influence their outcome. The influence of factors including age, sex, presence of osteoarthritis and size and site of lesion have been assessed individually and with multivariate analysis. All patients were assessed using the Bentley Functional Score, Visual Analogue Score and the Cincinnati Functional Score. Assessment were performed pre-operatively and of their status in 2010. The longest follow-up was 12 years (range 24 to 153 months) with a mean age of 34 years at time of procedure. The mean defect size was 409 mm2 (range 64 to 2075 mm2). The distribution of lesions was 51% Medial Femoral Condyle, 12.5% Lateral Femoral Condyle, 18% Patella (single facet), 5% Patella (Multifacet) and 6% Trochlea. 4% had cartilage transplant to multiple sites. High failure rates were noted in those with previous cartilage regenerative procedures or evidence of early osteoarthritis and those with transplantation to multiple sites. Autologous chondrocyte implantation is an effective method of decreasing pain and increasing function, however patient selection plays clear role in the success of such procedure.
Chondral injuries of the knee are extremely common and present a unique therapeutic challenge due to the poor intrinsic healing of articular cartilage. These injuries can lead to significant functional impairment. There are several treatment modalities for articular osteochondral defects, one of which is autologous chondrocyte implantation. Our study evaluates the mid to long term functional outcomes in a cohort of 828 patients who have undergone an autologous chondrocyte implantation procedure (either ACI or MACI), identifying retrospectively factors that may influence their outcome. The influence of factors including age, sex, presence of osteoarthritis and size and site of lesion have been assessed individually and with multivariate analysis. All patients were assessed using the Bentley Functional Score, Visual Analogue Score and the Cincinnati Functional Score. Assessment were performed pre-operatively and of their status in 2010. The majority of patients had several interim scores performed at varying intervals. The longest follow-up was 12 years (range 24 to 153 months) with a mean age of 34 years at time of procedure. The mean defect size was 486 mm2 (range 64 to 2075 mm2). The distribution of lesions was 51% Medial Femoral Condyle, 12.5% Lateral Femoral Condyle, 18% Patella (single facet), 5% Patella (Multifacet) and 6% Trochlea. 4% had cartilage transplant to multiple sites. 30% failed following this procedure at a mean time of 72 months. 52% patients stated a marked improvement in their functional outcomes within the first two years. 49% stated an excellent result following their procedure. High failure rate was noted in those with previous cartilage regenerative procedures, transplants occurring on the patella, particularly if involving multifacets. Multiple site cartilage transplantation was also associated with a high failure rate. Autologous chondrocyte implantation is an effective method of decreasing pain and increasing function, however patient selection plays clear role in the success of such procedure.
The aim of this study was to determine whether the clinical outcome of autologous chondrocyte transplantation was dependent on the timing of a high tibial osteotomy in tibio-femoral mal-aligned knees. Between 2000 and 2005, forty-eight patients underwent autologous chondrocyte implantation with HTO performed at varying times relative to the second stage autologous chondrocyte implantation procedure. 24 patients had HTO performed simultaneously with their second stage cartilage transplantation, (the HTO Simultaneous Group). 5 patients had HTO prior to their cartilage procedure, (the HTO pre-ACI Group) and 19 had HTO performed between 1 to 4 years after their second stage cartilage implantation, (the HTO post-ACI Group). There were 29 men and 19 women with a mean age of 37 years (Range 28 to 50) at the time of their second stage procedure. With average follow-up of 72 months we have demonstrated a significant functional benefit in performing the HTO either prior to or simultaneously with the ACI procedure in the mal-aligned knee. The failure rate in the Post-ACI group was 45% compared to the Pre-ACI and Simultaneous group, with failure rates of 20% and 25%, respectively. An HTO performed prior to or simultaneously with an autologous chondrocyte implantation procedure in the mal-aligned knee, provides a significant protective effect by reducing the failure rate by approximately 50%.
Autologous chondrocyte implantation (ACI) is contra-indicated in a joint rendered unstable by a ruptured anterior cruciate ligament (ACL). We present our experience of ACI repair with ACL reconstruction Patients underwent arthroscopic examination and cartilage harvesting of the knee. A second operation was undertaken approximately six weeks later to repair the ruptured ACL with hamstring graft or Bone patella-Bone (BPB) and to implant the chondrocytes via formal arthrotomy. Three groups were assessed: Group 1: Simultaneous ACL Reconstruction and ACI; Group 2: Previous ACL Reconstruction with subsequent ACI repair; Group 3: Previously proven partial or complete ACL rupture, deemed stable and not treated with reconstruction with ACI procedure subsequently. Patients then underwent a graduated rehabilitation program and were reviewed using three functional measurements: Bentley functional scale, the modified Cincinnati rating system, and pain measured on a visual analogue scale. All patients also underwent formal clinical examination at review.Introduction
Methods
Articular cartilage implantation (ACI) and associated procedures (MACI = Matrix-assisted cartilage implantation) are now established treatments for osteochondral defects in the knee. The quality of repair in terms of histological appearance is frequently not known, whilst the correlation of histology results with functional outcomes remains undefined. Histological data of the quality of the repair tissue is sparse and a precise classification proved difficult. This was a single-centre, prospective study. Over 12 years (1998-2010) 406 patients that underwent articular cartilage implantation procedures at our institution (ACI = 170, MACI = 205) had biopsies taken at the 1-2 year interval, in order to assess whether these contained ‘hyaline-like’ cartilage, ‘mixed hyaline-like with fibrocartilage’, fibrocartilage or fibrous tissue alone. Histological sections of the biopsies were prepared and stained with haematoxylin, eosin and proteoglycan stains and viewed under polarised light. All biopsies were studied by a single histopathologist in a specialist, dedicated musculoskeletal laboratory. All patients were assessed by the Cincinnati, Bentley and Visual Analogue scores both pre-operatively and at the time of the review. The findings revealed that 56 patients healed with ‘hyaline-like’ cartilage (14.9%), 103 with ‘mixed’ (27.5%), 179 with fibrocartilage (47.7%) and 37 with fibrous tissue (9.9%). These findings showed that 42.4% of defects were filled with ‘hyaline-like’ or ‘mixed’ cartilage, with 70% of these achieving a ‘fair’ to ‘excellent’ functional outcome. This was also observed in the fibrocartilage group, where 72% achieved similar results. Predictably 89% of the patients that healed by fibrous tissue had a poor functional outcome. This study shows that 71% of patients whose osteochondral defects healed by either ‘hyaline-like’, ‘mixed’ or fibrocartilage experienced an improvement in the function. In contrast, only 11% of the patients whose defects filled with fibrous tissue, showed some functional improvement. Additionally, this data indicates the advantage of biopsies in assessing the overall results of cartilage implantation procedures.
Patients with osteochondrodysplasia frequently require Total Hip Arthroplasty at a younger age, as a result of early degenerative disease of the hip joint. The outcome of Modular Total Hip Arthroplasty in this group of patients has been reported previously. In this retrospective study we evaluated the outcome of custom made (CADCAM) Total Hip Arthroplasty in patients with osteochondrodysplasia. Between 1974 and 2009, twenty one CADCAM Total Hip Arthroplasty procedures were performed in fourteen patients in our institution. There were eight female and six male patients, with the mean age at time of surgery of 40.95 years (20 to 78). The patients were followed up clinically and with the Harris hip score for a mean of 7.12 years (0.5 to 17 years). Four of the twenty-one hips (23.8%) required revision surgery at a mean of 11.54 years (6.5 to 17 years); one required it for aseptic loosening of the femoral component; one required complete revision of the acetabular component; one required exchange of acetabular liner; and one was for symptomatic non-union of a lesser trochanter avulsion. This study shows encouraging clinical outcomes of custom made (CADCAM) Total Hip Arthroplasty in patients with osteochondrodysplasia,
The rate of arthroplasty or osteotomy in patients who had undergone autologous chondrocyte implantation (ACI) for osteochondral defects in the knee was determined. Furthermore, we investigated whether any radiographic evidence of osteoarthritis (OA) prior to ACI was associated with poorer outcome following surgery. We retrospectively reviewed the medical notes and radiographs of 236 patients (mean age 34.9) who underwent ACI from 1998 to 2005 at our institution. Knee function was assessed according to the Modified Cincinnati Score (MCS) pre-operatively and at a mean of 64.3 months postoperatively (range 12 – 130). Radiographic changes were graded according to the Stanmore grading system.Purpose
Methods
We report the initial 2 and 3 year follow-up results of this randomised controlled trial of autologous chondrocyte implantation (ACI) using porcine-derived collagen membrane as a cover (ACI-C) versus matrix-carried autologous chondrocyte implantation (MACI) for the treatment of osteochondral defects of the knee. 217 patients were randomised to have either ACI (92 patients) or MACI (125 patients). The mean age in each group was 35.1 and 33 years respectively. There were equal proportion of males and females and there was no difference in the size of lesions in each of the treatment groups. One year following surgery, patients underwent check arthroscopy (with or without biopsy) to assess the graft. Functional assessment was performed yearly by using the Modified Cincinatti Knee score, the SF-36 score, the Bentley Functional Rating Score and the Visual Analogue Score.Introduction
Methods
The results for autologous chondrocyte implantation (ACI) in the treatment of osteochondral defects in the knee are encouraging. At present, two techniques have been described to retain the chondrocyte suspension within the defect. The first involves using a periosteal flap harvested from the distal femur and the second involves using a type I/III collagen membrane. To the authors' knowledge there are no comparative studies of these two techniques in the current literature. A total of 68 patients with a mean age of 30.52 years (range 15 to 52 years) with symptomatic articular cartilage defects were randomised to have either ACI with a periosteal cover (33 patients) or ACI with a type I/III collagen cover (35 patients). The mean defect size was 4.54 cm2 (range 1 to 12 cm2). All patients were followed up at 24 months. A functional assessment using the Modified Cincinnati score showed that 74% of patients had a good or excellent result following the ACI with collagen cover compared with 67% after the ACI with periosteum cover at 2 years (p>0.05). Arthroscopy at 1 year also demonstrated similar results for both techniques. However, 36.4% of the periosteum covered grafts required shaving for hypertrophy compared with 1 patient for the collagen covered technique. This prospective, randomised study has shown no statistical difference between the clinical outcome of ACI with a periosteal cover versus ACI with a collagen cover at 2 years. A significant number of patients who had the ACI with periosteum technique required shaving of a hypertrophied graft within the first year of surgery. We conclude that there is no advantage in using periosteum as a cover for retaining the chondrocytes within an osteochondral defect; as a result we advocate the use of an alternative cover such as a porcine-derived, type I/III collagen membrane.
To investigate (1) The relationship between macroscopic grading and durability of cartilage repair following collagen-covered autologous chondrocyte implantation (ACI-C) in the knee; (2) The influence of histology on durability of cartilage repair; (3) The relationship between macroscopic appearance and histology of repair tissue. The modified Cincinnati scores (MCRS) of eighty-six patients were evaluated prospectively at one year and at the latest follow-up (mean follow-up = 4.7yrs. Range = 4 to 7 years). Needle biopsies of their cartilage repair site were stained with Haematoxylin and Eosin and some with Safranin O and the neo-cartilage was graded as hyaline-like (n=32, 37.2%), mixed fibro-hyaline (n=19, 22%) and fibro-cartilagenous tissue (n=35, 40.7%). Macroscopic grading of the repair tissue using the international cartilage repair society grading system (ICRS) was available for fifty-six patients in the study cohort. Statistical analyses were performed to investigate the significance of histology and ICRS grading on MCRS at 1 year and at the latest follow-up.Aims
Patients and methods
We report on minimum 2 year follow-up results of 71 patients randomised to autologous chondrocyte implantation (ACI) using porcine-derived collagen membrane as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) for the treatment of osteochondral defects of the knee. ACI is used widely as a treatment for symptomatic chondral and osteochondral defects of the knee. Variations of the original periosteum-cover technique include the use of porcine-derived type I/type III collagen as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) using a collagen bilayer seeded with chondrocytes.Purpose
Introduction
Autologous chondrocyte implantation (ACII) has been shown to have favourable results in the treatment of symptomatic chondral and osteochondral lesions. However, there are few reports on the outcomes of this technique in adolescents. The aim was to assess functional outcome and pain relief in adolescents undergoing autologous chondrocyte implantation (ACI). Thirty-one adolescent patients undergoing ACI or Matrix-assisted chondrocyte implantation (MACI) were identified from a larger prospective study. Mean age was 16.3 years (range 14 – 18) with a mean follow-up of 66.3 months (12–126 months). There were 22 males and nine females. All patients were symptomatic; 30 had isolated lesions and one had multiple lesions. Patients were assessed pre and postoperatively using the Visual Analogue Score (VAS), the Stanmore/Bentley Functional Rating Score and the Modified Cincinnati Rating System. The mean VAS improved from 5.8 pre-operatively to 2 post-operatively. The Stanmore/Bentley Functional Rating Score improved from 2.9 to 0.9 whilst the Modified Cincinnati Rating System improved from 49.8 pre-operatively to 81.3 postoperatively with 87% of patients achieving excellent or good results. All postoperative scores exhibited statistically significant improvement from pre-operative scores. The results show that, in this particular group of patients, this procedure produces reduction in pain and a statistically significant improvement in function postoperatively. We strongly recommend this procedure in the management of adolescents with symptomatic chondral defects.
High Tibial Osteotomy (HTO) is a recognised method of correction for knee joint malalignment and unicom-partmental osteoarthritis. Long-term results of this technique have been reported and are favourable. Good results have also been reported with Autologous Chondrocyte Implantation (ACI-C, MACI). Malalignment, if present, should be corrected when ACI is performed. Although results have been reported for either procedure separately, the outcomes of combined HTO-ACI remain unreported. The aim of this study was to evaluate functional outcome in patients undergoing combined HTO-ACI procedures. Twenty three patients undergoing a combined ACI-HTO procedure were identified retrospectively from a larger trial of patients undergoing ACI for symptomatic chondral defects. The mean age of the patients was 36 (28 – 49). The mean follow-up was 54 months (12 – 108) and mean defect size was 689mm2 (range 350 – 1200). Nine patients had ACI-C and HTO, the remainder having MACI and HTO. Pre and post-operative assessment was carried out using the Visual Analogue Score (VAS), the Bentley Functional Rating Score and the Modified Cincinnati Rating System. The Mean VAS score improved from 7.4 (4 – 10) pre-operatively to 2.9 (0 – 6) post-operatively at the latest follow-up (p<
0.0001). The Bentley Functional Rating Score improved from 2.9 (2 – 4) to 1.8 (0 – 4), which was statistically significant (p<
0.0001). The Modified Cincinnati Rating System improved from 35.2 (20 – 49) pre-operatively to 68.7 (46 – 85) post-operatively (p<
0.0001). Fourteen patients underwent biopsy of the graft site at a mean of 13.7 months: 21% of biopsies were hyaline-like cartilage, 36% were mixed hyaline/fibrocartilage, 29 % were fibrocartilage and 14% were fibrous tissue. Combining high tibial osteotomy with autologous chondrocyte implantation is an effective method of decreasing pain and increasing function in the short term. Further evaluation of this procedure is required.
High tibial osteotomy (HTO) is a recognised method of correction for knee joint malalignment and unicompartmental osteoarthritis. The long term results of this technique have been reported and are favourable. Autologous chondrocyte implantation (ACI-C, MACI) has also been reported to have good results It is advised that malalignment, if present, should be corrected if ACI is to be performed. Although results have been reported for either procedure separately, the outcomes of combined HTO-ACI remain unreported. To evaluate functional outcome in a group of patients undergoing combined HTO-ACI procedures. Twenty three patients undergoing a combined ACI-HTO procedure were identified retrospectively from a larger trial of patients undergoing ACI for symptomatic chondral defects. The mean follow-up was 54 months (range 12 – 108) and the mean defect size was 689 mm2 (range 350 – 1200). Nine patients had ACI-C and HTO, the remainder having MACI and HTO. Pre and postoperative assessment was carried out using the Visual Analogue Score (VAS), the Bentley Functional Rating Score and the Modified Cincinnati Rating System. The Mean VAS score improved from 7.4 pre-operatively to 2.9 post-operatively (p<
0.0001). The Bentley Functional Rating Score improved from 2.9 to 1.8 (p<
0.0001) whilst the Modified Cincinnati Rating System improved from 35.2 pre-operatively to 68.7 post-operatively (p<
0.0001). There was no significant difference between ACI-C and MACI. Two patients developed a non union at a mean of 13 months and a further two patients had a failure of the chondrocyte graft at a mean of 22.5 months. Combining high tibial osteotomy with autologous chondrocyte implantation is an effective method of decreasing pain and increasing function at mean of 54 months follow-up. Further follow-up is required to assess the long term outcomes of these combined procedures.
Our statistical analysis suggests that if time post implantation doubles then the likelihood of a favourable histological outcome increases significantly.
Orthopaedic surgeons vary in their attitude towards resurfacing of the patella in total knee arthroplasty. Few studies are available to assess outcome and patient preference. We evaluated post-operative anterior knee pain and knee preference in patients with bilateral knee replacements and unilateral patellar resurfacing. We reviewed 30 patients who had undergone bilateral knee replacement with patellar resurfacing on only one side. Follow-up was from five to 12 years and the patients were assessed using the Knee Society rating, an anterior knee pain rating and a satisfaction score. Patients were also asked specifically if they had a preference for either knee. Assessment was performed without knowing which patella had been resurfaced. Fourteen patients (47%) favoured the resurfaced knee, six (20%) the un-resurfaced knee and 10 (33%) had no particular preference. The overall prevalence of anterior knee pain was 50% in the un-resurfaced cases (six mild, six moderate, three severe) and 20% in the resurfaced knees (four mild, two moderate). No significant difference was found between knee scores. Three un-resurfaced patellae have been secondarily resurfaced. This study shows a significant preference for the resurfaced side (p<
0.01), with a higher prevalence of anterior knee pain in non-resurfaced patellae (p<
0.05).
the influence of histology on durability of cartilage repair following collagen-covered autologous chon-drocyte implantation (ACI-C) in the knee. the relationship between macroscopic grading and durability of cartilage repair; and the relationship between macroscopic appearance and histology of repair tissue.
There was no correlation between the ICRS grading and MCRS either at one year (p=0.12) or at the latest follow-up (p=0.16). Also, the ICRS grading of the repair tissue did not correlate with its histological type (p=0.12).
The modified Cincinnati scores (MCRS) of eighty-six patients were evaluated prospectively at one year and at the latest follow-up following ACI-C (mean follow-up= 4.7 years. Range= 4 to 7 years). All these patients underwent biopsies of their cartilage repair site performed at variable periods between six months and five years following ACI-C (mean=22.2 months). The neo-cartilage was graded as hyaline (n=32), mixed fibrohyaline (n=19), fibrocartilagenous (n=35) and fibrous (n=0).
However, their clinical scores at the latest follow-up demonstrated a significantly superior result for those with hyaline repair tissue when compared to those with mixed fibro-hyaline and fibro-cartilagenous repair tissue (p=0.05). The percentage of patients with excellent and good results for those with hyaline, mixed fibro-hyaline and fibro-cartilagenous repair was 75, 42 and 68.6 respectively. Their mean MCRS were 70.6, 56.8 and 63.9 respectively.
Current bone grafts include allograft and autografts, both of which have limitations. Tissue engineering biotechnology has shown considerable promise in improving grafts. A competent graft material should ideally have osteoconductive and osteoinductive properties and comprise of bone forming cells and osteoinductive growth factors. In this study, we have evaluated the in vitro formation of bone and have used human demineralised bone matrix [DBM] and human insoluble collagenous matric [ICM] as scaffolds for mesenchymal stem cells [MSCs] and osteogenic protein [OP-1]. The objective was to determine whether combined addition of OP-1 and MSCs resulted in a superior bone graft substitute by improving the inherent osteoinductive property. DBM and ICM were prepared and combined with rhOP [1.4 mg/0.25 mg of bone] and MSCs [1 x 105/ ml]. Statistically significant differences in MSC proliferation were seen between materials with and without OP-1 [P<
0.05}, n=8] in DBM on day 1, and both DBM and ICM on day 7 and 14. Enhanced osteogenic differentiation was observed in the presence of OP-1 when compared to DBM alone and on DBM and ICM with OP-1. In conclusion MSCs and OP-1 can be seeded together on DBM and ICM and Von Kossa staining and X-ray analysis confirmed in vitro de novo bone formation, with DBM + MSCs + OP-1 being more successful in this regard.
Limitations of allografts and autografts for bone repair have increased the demand for a synthetic bone graft substitute for load-bearing and non-load bearing osseous defects. Tissue engineering of bone has thus been implicated to circumvent and eliminate the limitations of existing therapies, with living cell-scaffold constructs ultimately “integrating” with the patients own tissue. Bone engineering requires cells, growth inducing factors and a scaffold for delivery of cells to the anatomic site, creation of 3-D space for tissue formation and mechanical support. In this study, we investigated whether addition of osteogenic Protein-1 (OP-1) enhanced the osseoinductive properties of hydroxyapatite (HA) loaded with mesenchymal stem cells (MSCs). The study was conducted over a fourteen day period and the two groups HA/MSC and HA/MSC loaded with OP-1 were analysed qualitatively by SEM and quantitatively by assessment of proliferation (Alamar blue assay and total cellular DNA) and differentiation marker alkaline phosphatase activity (ALP). HA/MS/OP-1 showed a statistically significant (p<
0.05) increase in cell proliferation (286.52 ± 58.2) compared to the unloaded samples (175.62 ± 23.51). ALP activity (release) was also significantly enhanced (p <
0.05) in the loaded samples at day 14 (12.63 ± 1.58) compared to the control (2.73 ± 1.07).
Ninety knees were treated in the same centre between1995 and 1999 each had Low Contact Stress (LCS) knee prosthesis with patelloplasty; none of the patients had resurfacing of the patella. The average follow-up period was seven years (ranging from five to nine years). There were no exclusion criteria, almost all the patients included in this study were available for follow-up, the mean age was 75 years, and the majority of the patients were affected by osteoarthritis. All the operations were done by the same surgeon or under his supervision according to the protocol. Evaluation was performed with using The Knee Society Clinical Rating System and new Patellar Scoring System. The final scoring was done by an independent Senior Physiotherapist. The Knee Society’s radiological evaluation system was used to assess the pre and post-operative alignment of the knee and the prosthesis. Image Tool (IT accessories UTHSCSA) software used to for measurements of patellar tracking and alignments on the digitalised radiographs. Pre-operatively, the mean Knee Society score on a scale ranging from 0-200 points was 81.50 points (range 25 to 124 points); postoperatively this score improved to a mean of 150.76 points (range 46 to 195 points). Statistical analysis using paired-comparison t-tests showed the score differences were statistically significant at p-values <
0.0001. None of the patients required resurfacing during the follow-up. There were no reported cases of significant anterior knee pain, dislocation, maltracking or fractured patella.
Clinical outcomes during the first two postoperative years did not vary according to repair morphology type, though hyaline repair was associated with better clinical outcomes beyond 2 years; At 1 year, good to excellent clinical scores were observed in 29 (78.4%) patients with hyaline-like repair, 23 (76.7%) patients with fibrohyaline repair, and 54 (74.0%) patients with fibrocartilage repair. By years 3 and 4 post-implantation, clinical scores further improved in patients with hyaline-like repair yet declined in those with fibrocartilage and fibrohyaline. The difference was significant at 3 years though not at 4 due to the small number of cases.
These figures represent the early results of this study performed at this unit.
The mean Harris hip score increased from 44 points (range, 27 to 71 points) preoperatively to 71 points (range, 21 to 98 points) at the time of the most recent follow-up. 9 patients required subsequent revision; 4 for aseptic loosening, 1 for septic loosening and 4 for fracture of the femoral component.
Autologous Chondrocyte Implantation (ACI) is a technique for repair of isolated symptomatic articular cartilage defects in the young adult knee. The knee is arthroscopically assessed and a sample of cartilage is harvested from the margin of the joint, this is digested and the liberated chondrocytes expanded in culture. At subsequent arthrotomy, the articular cartilage lesion is debrided and the cells injected behind a sutured flap. A concern regarding ACI is the iatrogenic insult to non-injured healthy cartilage adjacent to that harvested for culture. Damaged cartilage around the lesion is routinely debrided and discarded at the second stage operation. The purpose of this study was to determine whether this damaged debrided cartilage could yield an adequate number of equivalent chondrocytes for ACL. Cells from 11 patients were analysed. The debrided “waste” from around the lesion was collected, enzymatically digested and the liberated chondrocytes cultured in monolayer. The cells were recovered and placed in a 3D-pellet culture in a defined medium. Chondrocytes obtained from the routine harvest of healthy cartilage were placed in a similar culture system. The two groups were compared using DNA and GAG assays, histological and immunohistochemical techniques. Chondrocytes obtained from the debrided cartilage lesion were equivalent to those obtained from the harvested healthy cartilage. Sufficient cell numbers for implantation were achieved for all patients, however cells cultured from the debrided defect in patients who had a large degenerate lesion required significantly longer in culture to attain the required number of cells. For many patients undergoing ACI, the potential iatrogenic insult to the joint cartilage of the harvesting procedure could be avoided by harvesting the damaged tissue from around the defect itself.
Mosaicplasty 100 consecutive patients aged 15–45 with a symptomatic articular cartilage lesion in the knee suitable for cartilage repair were randomised at arthroscopic assessment to undergo either mosaicplasty or ACI. 42 patients underwent mosaicplasty, 58 had ACI. Mean age at time of surgery was 31 years and the average defect size 4. 66 cm2. 46% of the defects were post-traumatic, 19% had osteochondritis dissecans, 14% had chondromalacia patella and 16% had lesions of unknown aetiology. 53% had a medial femoral condyle lesion, 25% patella, 18% lateral femoral condyle, 3% trochlea and there was one defect of the lateral tibial plateau. The mean duration of symptoms was 7. 2 years and the average number of previous operations (excluding arthroscopies) was 1. 5. Only 6 patients had no prior surgical interventions to the affected knee. The mean follow-up was 1. 7 years. Patients were evaluated using Modified Cincinnati and Stanmore Functional rating systems, visual analogue scores and clinical assessment. Arthroscopy and biopsy was performed at one year and repair assessed with the International Cartilage Repair Society grading system. Clinical results at one year showed 70% of mosaic-plasty patients and 87% of ACI patients had a good or excellent result. Arthroscopy at one year demonstrated more complete healing in ACI patients. Eleven (26%) of the mosaicplasty group subsequently failed clinically and arthroscopically, with peak failure at 2 years. At one year follow-up, both techniques of articular cartilage repair can be useful in selected patients. ACI is preferred for lesions of the patella. Long-term follow-up is needed to assess the durability of articular cartilage repair using these methods, in particular mosaicplasty which showed signs of progressive failure over 2 years.
Autologous Chondrocyte Implantation’ (ACI) is a cartilage repair technique that involves implantation of cultured chondrocytes beneath a membrane of autologous periosteum. In this study a porcine biodegradable membrane was also used to assess its effectiveness. The aim is to restore articular cartilage to symptomatic defects, rather than initiating a fibrocartilagenous repair. We undertook a prospective study of 125 consecutive patients who underwent ACI. Average age at the time of surgery was 30. 9 years (range 14 – 49), 55% of patients were male. The average size of the defect was 4. 35 cm². 44% of defects were attributable to known traumatic incidents, 2 1 % had osteochondritis dessicans, 18% chondromalacia patella, 12% had defects of unknown aetiology and 5% other. The average duration of symptoms prior to this surgery was 7. 16 years. The mean number of previous operations (excluding arthroscopies) was 1. 6. Only 9 patients had no previous major surgery to the affected knee. 44% had defects of the medial femoral condyle, 31% patella, 20% lateral femoral condyle and 5% had a trochlea lesion. 26% of the defects were covered with periosteum and 74% with a porcine collagen membrane (chondrogide) Minimum follow-up was six months, 70 patients had minimum follow-up of one year. Mean follow-up 18 months. Patients were assessed using Modified Cincinnati and Stanmore Functional rating systems, visual analogue scores and clinical evaluation. Arthroscopy and biopsy was performed at one year and the repair assessed using the International Cartilage Research Society grading system. At one year follow-up overall 41 % patients had an excellent result, 48% good, 8% fair and 3% poor. For defects of the medial femoral condyle, 88% had a good or excellent result, 85% for the lateral femoral condyle and 80% for the patella. 61 patients were arthroscopically assessed at one year. 50/61 (82%) demonstrated ICRS grade 1 or 2 repair. Healing of the defect occurred with either a periosteum or chondrogide defect cover. Results at one year suggest that ACI is a successful articular cartilage repair technique in selected patients. Long-term follow-up is required to assess the durability of the repair.
The clinical results of carbon matrix support prostheses for treatment of articular cartilage defects of the femoral condyle and patella were assessed in 97 patients (100 prostheses) between 1989–99. Patients were independently reviewed by subjective and objective criteria. Pre-operative and current visual analogue scores for pain (VAPS); Stanmore and modified Cincinnati functional rating scores were obtained. Forty-nine patients had lesions of the patella, forty-four patients of the medial femoral condyle and seven patients of the lateral femoral condyle. Patella group – subjectively 49% reported they were improved, 8% unchanged and 43% worse. Stanmore score: 6 excellent and 17 good (47%), 5 fair and 21 were poor. The Cincinnati score increased from 26. 5 pre-operatively to 47. 5 currently (p<
0. 001). The mean VAPS decreased from 8. 1 to 5. 0 (p<
0. 001). Medial femoral condyle group – subjectively 60% reported they were improved, 14% unchanged and 26% worse. Stanmore score: 8 excellent and 16 good (55%), 8 fair and 12 poor. The Cincinnati score increased from 22. 3 pre-operatively to 48. 5 currently (p<
0. 001). The mean VAPS decreased from 8. 6 to 5. 1 (p<
0. 001). Lateral femoral condyle group – subjectively 42% reported they were improved, 29% unchanged and 29% worse. Stanmore score: 2 excellent and 1 good (43%), 2 fair and 2 poor. The Cincinnati score increased from 35. 0 pre-operatively to 52. 0 currently (p<
0. 25). The mean VAPS decreased from 6. 5 to 4. 0 (p<
0. 25). There were no statistical differences in outcome based upon gender, site, pre-operative functional rating score, diagnosis, or any correlation with age or length of follow up, or when comparing excellent/good with fair/ poor subgroups in patellae or femoral condyles in relation to these variables. This study demonstrated that 49% improved in the patella group, 60% in the medial femoral condyle and 43% in the lateral femoral condyle groups. The use of these prostheses was effective on the medial femoral condyle for periods up to 10 years but the use in the patella and lateral femoral condyle was less successful.
The use of intra-articular hyaluronic acid injections for the treatment of early osteoarthritis is in widespread clinical use. Hyaluronate (HA) is a major component of connective tissue Bovine articular chondrocytes were isolated by sequential digestion with pronase and collagenase and seeded in 2% alginate at 1x107 cells/ml. The constructs were cultured for up to 14 days in standard culture medium (DMEM + 20% Fetal calf serum) containing varying concentrations of HA (Sigma), including doses equivalent to those found in vivo. The medium was replaced every 3 days and representative constructs were removed from culture, digested and assayed for DNA, glycosaminoglycans and Collagen. Further constructs were fixed in 4% paraformaldehyde for standard histology and immunolocalisation of collagen types I, II and chondroitin-6-sulphate. Chondrocytes cultured in the HA system proliferated (increase in DNA) at a faster rate than the controls. There was a 2.2 fold increase in cell concentration at 14 days compared to a 1.2 fold increase in the controls. Total GAG levels at each time point were significantly greater for cells cultured in HA than in controls. Histologically, constructs were characterised by extensive cell cluster formation and intense Safranin-O staining. The newly synthesised matrix also stained positive for type II collagen. By contrast, control constructs exhibited minimal cluster formation, Safranin-O and type II collagen staining. Cells maintained with HA exhibited a significantly greater rate of proliferation and matrix production. The presence of matrix rich in type II collagen indicates maintenance of chondrocytic phenotype. By contrast, cells cultured without HA did not show these features. These results support the use of intra-articular injections for the treatment of osteoarthritis. The benefits of HA injections may be due to cellular mechanisms as well as mechanical.
The use of intra-articular corticosteroid injections for their anti-inflammatory effects is widespread amongst clinicians. Despite their use in both rheumatoid arthritis and osteoarthritis, the effect of these agents on articular chondrocytes is not fully established. Previous reports suggest a detrimental effect on cartilage explants resulting from inhibition of matrix synthesis Bovine articular chondrocytes were isolated by sequential digestion with pronase and collagenase and seeded in 2% alginate at 1x107 cells/ml. The constructs were cultured for up to 15 days in standard culture medium (DMEM + 20% Fetal calf serum) containing varying concentrations of MP, including doses equivalent to those found in vivo. The medium was replaced every 3 days and representative constructs were removed from culture, digested and assayed for DNA and glycosaminoglycans. Further constructs were fixed in 4% paraformaldehyde for standard histology and immunolocalisation of collagen types I, II and chondroitin-6-sulphate. Chondrocytes cultured in MP containing medium showed a significant abnormality in cell morphology compared to controls at the day 15 time point. Histologically there was evidence of cell necrosis, reduced amounts of extracellular matrix and loss of collagen type II staining. The effects were dose dependant, with significant damage occurring even at clinical doses. Biochemical analysis revealed a reduction in DNA content and an inhibition of glycosaminoglycan and collagen type II synthesis. In contrast, in the controls, there was cell proliferation with a cell doubling time of 14 days, collagen type II containing extracellular matrix synthesis occurred and the chondrocytes maintained their phenotype throughout the culture period. Methylprednisolone has a significant detrimental effect on cultured articular chondrocytes in vitro. There was significant cell necrosis associated with inhibition of extracellular matrix synthesis. Based on these results, intra-articular corticosteroid injections should be used with extreme caution.
Nicotine is a constituent of tobacco smoke and is present in the body fluids of smokers Bovine nucleus pulposus (NP) intervertebral disc cells were isolated by sequential digestion of caudal spinal disc nuclei with pronase and collagenase and seeded in 2% alginate at 5x106 cells/ml. The constructs were cultured for 21 days in standard culture medium (DMEM + 20% Fetal calf serum) containing free base nicotine (Sigma) at concentrations ranging from 25nM and 300nM, which reflected the normal physiological concentrations found in the serum of smokers. The medium was replaced every 3 days and representative constructs were removed from culture, digested and assayed for DNA, glycosaminoglycan (GAG) and hydroxyproline content at time points 3, 7, 14 and 21 days. Further constructs were processed for standard histology and immunolocalisation of collagen types I, II and chondroitin-6-sulphate. The results were analysed statistically using an ANOVA test followed by a non-parametric Dunnit’s test. NP cells demonstrated a dose dependent response. At 25nM dose of nicotine there was a significant increase (p<
0.05) in DNA content, GAG and collagen synthesis in the constructs. At 100nM, 200nM and 300nM doses, there was a significant dose dependent decrease (p<
0.05) in all of these parameters compared to controls cultured under nicotine free conditions. In addition, adverse morphological changes were observed on histology, which included reduced cell proliferation, disrupted cell architecture, disintegration of cells and extracellular matrix. Immunohistochemistry showed the production of type I collagen rather than type II collagen as in the controls. Nicotine has an overall detrimental effect on cultured nucleus pulposus disc cells in vitro. There was significant inhibition of cell proliferation and extracellular matrix synthesis. Nicotine in tobacco smoke may therefore play a role in the aetiology of disc degeneration that leads to back pain in smokers.
Deep infection is a devastating complication of total joint arthroplasty. In a significant proportion of cases it remains a diagnostic challenge. Haematological tests are not specific, particularly in chronic cases, and radiological investigations such as bone scan and radiographs are of only limited value. The most common infective organisms are staphylococcus and some streptococcus species. Acidity is a well established occurrence in infective processes and is caused by the direct production of acid by the organism or by enzymatic degradation of tissues Nineteen consecutive patients undergoing either revision total knee replacement (TKR) or arthroscopic synovial biopsy were included in the study. All had had their primary joint replacement within the previous 3 years. All had a painful total knee replacement and some had evidence of loosening of the prosthesis on radiological investigations. The following investigations were performed on each patient, White cell count (WCC), Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), interface synovial biopsy for histology and microbiology and a synovial fluid aspiration from the affected joint prior to application of a tourniquet. A blood gas analyser was used to measure pH, pCO2, pO2, Lactate and Glucose in all synovial fluid specimens. Seven patients were diagnosed as having an infected TKR on clinical and laboratory investigations. The mean synovial fluid biochemistry results were pH = 7.09, pO2= 5.08kPa, pCO2=10.40kPa, Lactate = 5.33 mmol/l, Glucose = 2.30 mmol/l. In the non-infected group the results were pH = 7.23, pO2 = 7.72kPa, pCO2 = 8.41kPa, Lactate = 4.03 mmol/l, Glucose = 3.42 mmol/l. The differences in pH, pCO2/pO2 ratio, and glucose levels were statistically significant (t-Test p <
0.05) between the two groups. Lactate levels were not significantly different. There was no correlation between high WCC’s and synovial fluid biochemistry or laboratory results for infected cases. Using laboratory results as a gold standard and a synovial fluid pH of less than 7.20, the sensitivity was 85% and specificity 77% for diagnosing an infection. Using a combination of the synovial fluid biochemistry results these values were greater. Synovial fluid biochemistry is significantly altered in infected total knee replacements. pH levels below 7.2, pCO2/pO2 ratio above 2.5 and Glucose levels below 2.5 mmol/l are strong indicators of an infected TKR. Synovial pH assessment may prove to be a quick, cheap and effective method of diagnosing an infected TKR and may also apply to other joints. Further studies using non-problematic TKR’s as controls are required.