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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_13 | Pages 41 - 41
7 Aug 2023
Al-Jabri T Bentley G McCulloch R Miles J Carrington R Shearman A Donaldson J Jayadev C
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Abstract

Background

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.

Methodology

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.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_13 | Pages 21 - 21
1 Mar 2013
RAHMAN J KAYANI B GILLOTT E BENTLEY G SKINNER J MILES J CARRINGTON R BRIGGS T
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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.

RESULTS

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.

CONCLUSIONS

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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXIX | Pages 90 - 90
1 Sep 2012
Nawaz S Gallagher K Dhinsa B Carrington R Skinner J Briggs T Bentley G
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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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 571 - 571
1 Sep 2012
Nawaz S Bentley G Briggs T Carrington R Skinner J Gallager K Dhinsa B
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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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 69 - 69
1 Aug 2012
Picardo N Nawaz Z Gallagher K Whittingham-Jones P Parratt T Briggs T Carrington R Skinner J Bentley G
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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%.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 40 - 40
1 Aug 2012
Dhinsa B Nawaz S Gallagher K Carrington R Briggs T Skinner J Bentley G
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Introduction

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

Methods

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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 12 - 12
1 Aug 2012
Shekkeris A Perera J Bentley G Flanagan A Miles J Carrington R Skinner J Briggs T
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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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXV | Pages 43 - 43
1 Jun 2012
Dhinsa B Jalgaonkar A Nawaz Z Briggs T Muirhead-Allwood S Carrington R Skinner J Bentley G Miles J
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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,


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXV | Pages 44 - 44
1 Jun 2012
Dhinsa B Nawaz Z Gallagher K Carrington R Skinner J Briggs T Bentley G
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Purpose

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.

Methods

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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_IV | Pages 131 - 131
1 Mar 2012
Jaiswal P Park D Carrington R Skinner J Briggs T Flanagan A Bentley G
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Introduction

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.

Methods

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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 122 - 122
1 Feb 2012
Gooding C Bartlett W Bentley G Skinnner J Carrington R Flanagan A
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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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_III | Pages 155 - 155
1 Feb 2012
Krishnan S Skinner J Jaggiello J Carrington R Flanagan A Briggs T Bentley G
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Aims

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.

Patients and methods

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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_III | Pages 153 - 153
1 Feb 2012
Park D Krishnan S Skinner J Carrington R Flanagan A Briggs T Bentley G
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Purpose

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.

Introduction

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.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 472 - 472
1 Nov 2011
Macmull S Parratt M Bentley G Skinner J Carrington R Briggs T
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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.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 292 - 292
1 Jul 2011
Parratt M Macmull S Gikas P Gokaraju K Carrington R Skinner J Bentley G Briggs T
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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.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 287 - 287
1 Jul 2011
Gikas P Parratt T Carrington R Skinner J Bentley G Briggs T
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Introduction: Autologous Chondrocyte Implantation (ACI) is a treatment option for symptomatic, full-thickness chondral/osteochondral injuries. Goals of surgery and rehabilitation include replacement of damaged cartilage with hyaline/hyaline-like cartilage, leading eventually to improved level of function. Intermediate and long-term results are promising in terms of functional improvement.

Purpose: To explore the hypothesis that non-hyaline cartilage repair tissue is associated with worse functional outcome and to assess whether the quality of the repair tissue formed following ACI improves with time post-surgery.

Methods and Results: Two hundred and forty eight patients who underwent ACI at our institution were studied, having had post-implantation biopsies of the repair tissue. Mean timing of biopsy was 14.8 months (range 3–55). 59 biopsies showed hyaline tissue (24%), 67 mixed hyaline and fibrocartilage (27%), 113 biopsies were fibrocartilage only (46%) and 9 patients had a fibrous tissue biopsy result (9%). 126 patients (51%) had hyaline tissue in the regenerate and demonstrated a mean Modified Cincinnati Rating Score (MCRS) of 84 and a mean Lysholm Score of 88 at last follow-up (Group 1). 122 patients (49%) had no hyaline tissue in the regenerate and scored a mean MCRS of 71 and a mean Lysholm Score of 73 (Group 2). Both Groups 1 and 2 demonstrated a statistically significant improvement in functional outcome between pre and post-operative scores (p< 0.0001). There was significant difference in post-operative scores between Groups 1 and 2 suggesting that presence of hyaline tissue in the regenerate is associated with improved functional outcome (p< 0.05). Finally, our statistical analysis suggested that if time post-implantation doubles, then the likelihood of a favourable histological outcome increases significantly.

Conclusion: ACI forms a durable repair tissue that remodels and continues to improve in quality with time. Poor functional outcome may reflect the presence of a non-hyaline cartilage repair tissue.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 287 - 287
1 Jul 2011
Jaiswal P Macmull S Bentley G Carrington R Skinner J Briggs T
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Introduction: Autologous chondrocyte implantation (ACI) has been used to treat patella cartilage lesions but several studies have indicated poorer results compared to lesions on the femoral condyles. This paper investigates the effectiveness of two different methods of ACI; porcine-derived collagen membrane as a cover (ACI-C) and matrix-carried autologous chondrocyte implantation (MACI).

Methods: 124 patients (mean age 33.5) with symptomatic osteochondral lesions in the patella were selected to undergo either ACI (56 patients) or MACI (68 patients). 1 year following surgery patients underwent check arthroscopy to assess the graft. Functional assessment was performed pre-operatively, at 6 months and yearly by using the modified Cincinnati score (MCS).

Results: 37.5% of patients experienced good or excellent clinical results according to the MCS in the ACI group compared with 69.2% in the MACI group (p = 0.0011). The mean MCS improved from 43.7 pre-operatively to 49.8 2 years following surgery in the ACI group, whereas in the MACI group the improvement was from 44.6 to 60.6 (p=0.07). Arthroscopic assessment showed a good to excellent International Cartilage Repair Society score in 89.7% of ACI-C grafts and 69.6% of MACI grafts (p = 0.08). There was a higher re-operation rate (p = 0.044) in the ACI group (29%) compared with MACI (10%).

Conclusions: The results from this paper suggest that MACI is more successful in the treatment of patella cartilage lesions than ACI even though arthroscopic assessment showed the converse to be true. The higher complication and re-operation rate suggests that we should be treating such patients with MACI.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 92 - 92
1 May 2011
Parratt M Nawaz Z Gikas P Carrington R Skinner J Bentley G Briggs T
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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.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 411 - 412
1 Jul 2010
Gikas P Carrington R Skinner J Briggs T Bentley G
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Introduction: Autologous Chondrocyte Implantation (ACI) is a treatment option for full-thickness chondral, or osteochondral injuries that are painful and debilitating. Goals of surgery and rehabilitation include replacement of damaged cartilage with hyaline or hyaline-like cartilage, leading eventually to improved level of function. Intermediate and long-term results are promising in terms of functional and clinical improvement.

Purpose: To explore the hypothesis that the quality of the repair tissue, formed following Autologous Chondrocyte Implantation (ACI), improves with time post-surgery.

Methods and Results: Two hundred and forty eight patients who underwent autologous chondrocyte implantation in our institution were studied after having had post implantation biopsies of the repair tissue. Mean timing of biopsy was 14.8 months (range 3–55). 59 biopsies gave hyaline tissue (24%), 67 mixed hyaline and fibrocartilage (27%), 113 biopsies were fibrocartilage only (46%) and 9 patients had a fibrous tissue biopsy result (9%). Due to NHS restraints and waiting list targets biopsies were actually performed at various time points post implantation allowing us to statistically correlate histological findings with the maturity of the repair tissue.

Our statistical analysis suggests that if time post implantation doubles then the likelihood of a favourable histological outcome increases significantly.

Conclusion: Autologous chondrocyte implantation forms a durable repair tissue that remodels and continues to improve in quality with time. It is recommended that for future research/study purposes 24 months is used as an optimal time to look at histology, since our data show that outcome is still improving until this point.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 317 - 317
1 May 2010
Bayliss L Jameson-Evans M Hanna S Gikas P Carrington R Briggs T Skinner J Bentley G
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Introduction: Initial results for the management of osteochondral defects with both ACI-C and MACI have been encouraging, showing significant clinical improvement. This single-centre study set out to determine any significant difference in outcomes between ACI-C and MACI.

Aim: Reporting three year follow up of clinical and arthroscopic assessment of prospective analysis of ACI-C and MACI used in the management of symptomatic, full-thickness chondral and osteochondral defects in the knee.

Method: Following assessment arthroscopy and harvesting of chondrocytes for culture, patients were randomised into the ACI-C or MACI arm and underwent their respective procedures one month later. In ACI-C a covered technique is employed using a porcine-derived type I/III collagen membrane sutured in place; MACI requires cultured autologous chondrocytes to be seeded in a bi-layered type I/III collagen membrane which is glued into position. An arthroscopy was performed at 12 and 24 months postprocedure to assess graft coverage and biopsies taken to determine extent of hyaline, mixed and fibro-cartilage proliferation.

Results: 102 patients underwent either ACI-C (44) or MACI (58) with an average age of 33.6 (14–52). Mean Cincinnati knee rating scores recorded prior to assessment arthroscopy for ACI-C: 45.2 (10 – 94) and MACI: 45.5 (10 – 90) showed improvement at follow up with 63% of patients in the ACI-C group scoring good or excellent at three years, and 60% in the MACI group. ICRS arthroscopy scores were good or excellent in 91.4% of ACI-C and 76.1% of MACI patients at 24 months. Biopsies of the transplants at 24 months revealed proliferation of hyaline and mixed cartilage (hyaline and fibro-cartilage) in 48.6% of the ACI-C and 30.5% of the MACI patients.

Conclusion: Results to date suggest significant clinical and arthroscopic improvement following ACI-C and MACI, with evidence of proliferation of hyaline cartilage at the transplant site. Limited differences are noted between the outcomes of the two techniques.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 321 - 322
1 May 2010
Jaiswal P Park D Carrington R Skinner J Briggs T Bentley G
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Purpose: We attempted to identify whether patients with early evidence of osteoarthritis (OA) on their pre-operative radiographs were associated with poorer outcomes after Autologous Chondrocyte Implantation (ACI).

Methods: We retrospectively reviewed radiographs of 94 consecutive patients who underwent ACI and had already had their knee function assessed according to the Modified Cincinatti Score 2 years following surgery. Changes were graded according to The Kellgren and Lawrence (K& L) and the Stanmore grading system. Two independent observers analysed the films to assess the reproducibility and accuracy of these grading systems for assessment of OA in the knee.

Results: Patients were divided into 2 groups; Group A were patients with excellent/good outcome (52 patients), those with fair/poor outcome were Group B (42 patients).13 patients in Group A and 21 patients in Group B had radiographic evidence of OA (p< 0.025). In 34 patients who had OA (mean age 33.6) the increase in Cincinatti score following surgery was minimal (33.5 to 37.5). In 60 patients where there was no evidence of OA (mean age 33.7) the score increased from 40 to 53.4. The inter-observer variation was greater using K& L (Kappa=0.31) compared with the Stanmore grading systems (Kappa=0.72).

Conclusions: Patients with early radiographic evidence of OA are unlikely to gain maximum benefit from ACI. Furthermore, we recommend the use of Stanmore grading system for the assessment of OA as it is more reproducible than the K& L grading system.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 124 - 124
1 Mar 2010
Parratt M Waters T Carrington R Skinner J Bentley G
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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).


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 84 - 84
1 Mar 2009
Jaiswal P Park D Jagiello J Carrington R Skinner J Briggs T Bentley G
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Introduction: Smoking is associated with impaired wound healing, delayed bony union following fractures and an adverse effect on the immune system. Furthermore, smoking is an important risk factor for the development pulmonary complications following major surgical procedures, as well as wound complications. We determined whether smoking had a deleterious effect on outcome after autologous chondrocyte implantation (ACI) in the treatment of ostechondral defects of the knee.

Methods: We identified 103 (54 females and 49 males) patients with a mean age of 34.2 (range 18 to 49) who had undergone ACI between January 2001 and August 2004 who also had their smoking status recorded. The patients were divided into 3 groups according to their smoking status. The Visual Analogue Score, Bentley Functional Rating Score and Modified Cincinatti Scores were used to assess function pre-operatively, 6 months and then yearly thereafter.

Results: Group 1 consisted of 31 smokers (mean pack years of 13.4), group 2 consisted of 63 non-smokers and group 3 contained 9 ex-smokers. In Group 1, the Modified Cincinatti Score pre-operatively, 6 months, 1 year and 2 years following surgery were 34.1, 42.6, 43.5 and 46.7 respectively. In group 2 the scores were 47.4, 59.6, 59.1, 65.3, and in group 3 the scores were 39.8, 50, 53.3, 51.8. At the 1 year check arthroscopy, the graft failure rate in group 1 was 12% and biopsies revealed mixed hyaline and fibrocartilage in only 25% (there were no patients with hyaline cartilage). There were no graft failures in group 2 and 43.8% of the biopsies performed were either hyaline (12.5%) or mixed hyaline and fibrocartilage (31.3%). The wound complication rate was 24% in group 1 and 8% in group 2.

Conclusions: The results of this study suggest that people who smoke have a worse functional outcome and a higher complication rate following chondrocyte implantation. This association has not been previously described and should be included in the pre-operative counselling of patients undergoing the procedure.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 84 - 84
1 Mar 2009
Jaiswal P Park D Jagiello J Carrington R Skinner J Briggs T Bentley G
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Introduction: Several studies have implicated excessive weight as a negative predictor of success of total knee arthroplasty. In addition, obese patients are known to have increased risk of wound complications after orthopaedic and general surgery. The purpose of this study was to compare the clinical and functional outcomes of autologous chondrocyte implantation for treatment of osteochondral defects of the knee performed in obese patients with those performed in non-obese patients.

Methods: We analysed the data on all our patients that have been followed up for a minimum of 2 years and had their height and weight recorded initially in our database. Functional assessment consisted of Bentley Functional Rating Score, Visual Analogue Score, and the Modified Cincinatti Scores (collected prospectively at 6 months, 1 year, 2 years and 3 years following surgery). Patients were placed into 3 groups according to their body mass index (BMI). Group A consisted of patients with BMI of 20 to 24.9, group B patients with BMI of 25 to 29.9 and Group C are patients with BMI of 30 to 39.9.

Results: There were 80 patients (41 males and 39 females) with a mean age of 35.4 (range 18 to 49). The mean BMI for the entire group was 26.6. The pre-operative, 6 month, 1 year, 2 year, and 3 year Modified Cincinatti Score in Group A (32 patients) was 54.4, 80.3, 82.7, 74.7 and 72.6. Similarly in Group B, the scores were 53, 41, 54, 56, 49.5 and in Group C the scores were 36.3, 36.3, 49.6, 36, and 35.7. The wound infection rate in Group A was 6.25%, in Group B was 17.6% and Group C was 14.3%.

Conclusions: Initial results from this study suggest that BMI is an important predictor of outcome after chondrocyte implantation. The group of patients that would gain most benefit from ACI are patients that are not overweight (defined by BMI in the range of 20 to 24.9). Further work is being carried out to support the hypothesis that surgeons should strongly consider not operating on patients unless the BMI is less than 25.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 84 - 84
1 Mar 2009
Jaiswal P Park D Carrington R Skinner J Briggs T Flanagan A Bentley G
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Introduction: 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. We report the minimum 2 year follow-up results of 192 patients randomised to autologous chondrocyte implantation (ACI) using porcine-derived collagen membrane as a cover (ACI-C) and matrix-induced autlogous chondrocyte implantation (MACI) for the treatment of osteochondral decfects of the knee.

Methods: 192 patients (mean age 34.2) were randomised to have either ACI (86 patients) or MACI (106 patients). 1 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 Bentley functional rating score and the visual analogue score.

Results: 24 patients were excluded from the study as they underwent additional procedures (e.g. high tibial osteotomy). In the ACI group the modified Cincinatti score increased from 42.5 pre-operatively to 56.7, 54.1, and 60.4 at 1 year, 2 years and 3 years respectively. In the MACI group the Cincinatti scores increased from 46.0 pre-operatively to 59.9, 58.9, and 58.4. Arthroscopic assessment showed a good to excellent International Cartilage Repair Society score in 90.7% of ACI-C grafts and 68.4% of MACI grafts. Hyaline-like cartilage or hyaline-like with fibrocartilage was found in biopsies of 51.9% of ACI-C grafts and 25.9% of MACI grafts.

Conclusions: ACI grafts are more likely to produce hyaline-like or mixed hyaline-like cartilage and fibro-cartilage with better ICRS grades than MACI grafts. However, this does not translate to better a clinical functional outcome. More importantly, ACI and MACI had similar results that were maintained at 3 years.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 578 - 578
1 Aug 2008
Jameson-Evans M Jaiswal PK Park DH Carrington RWJ Skinner JA Briggs TWR Bentley G
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Aims: he purpose of this study was to determine whether autologous chondrocyte implantation (ACI) in patients with articular cartilage defects of the knee resulted in patients returning to pre-injury levels of work and physical activities.

Methods: 133 consecutive patients from January 2001 to December 2002 underwent ACI at our institution. A telephone and postal questionnaire was conducted to ascertain a detailed occupational and leisure activity profile in this cohort of patients. For each job held for at least 2 months, we asked whether an average working day had involved any of the ten specified physical activities. Similarly, for each sport that had been played more than 5 times a year, we asked the age the sporting activities had began and whether they were able to return to these sports after surgery. Occupation for each patient was given a 3 digit code according to the Standard Occupational Classification System 2000 and hence determined whether the work performed was manual or non-manual.

Results: 97 patients responded to the questionnaire. There were 53 females and 44 males and the mean age at the time of operation was 34.5 (range 14 to 49). Category 6 (Personal Services Occupations) was the most common occupation pre-operatively, whereas category 4 (Administrative and Secretarial Occupations) was the most common post-operatively. 7% of patients’ work involved kneeling or squatting and this figure rose to 12%, 4 years following surgery. 42% of patients had to make some form of modification to their work (usually less physical or more office based). 47% of patients were able to return to at least one of the sports they played pre-injury.

Conclusion: This is the first study to demonstrate that patients are able to return to work and resume sporting activity following autologous chondrocyte implantation.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 578 - 578
1 Aug 2008
Jaiswal P Jameson-Evans M Jagiello J Carrington R Skinner J Briggs T Bentley G
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Aims: To compare the clinical and functional outcomes of autologous chondrocyte implantation for treatment of osteochondral defects of the knee performed in overweight, obese and patients of ‘ideal weight’as defined by their BMI.

Methods: We analysed the data on all our patients that have been followed up for a minimum of 2 years and had their height and weight recorded initially in our database. Functional assessment consisted of the Modified Cincinatti Scores (collected prospectively at 6 months, 1 year, 2 years and 3 years following surgery). Patients were placed into 3 groups according to their body mass index (BMI). Group A consisted of patients with BMI of 20 to 24.9, group B patients with BMI of 25 to 29.9 and Group C are patients with BMI of 30 to 39.9.

Results: There were 80 patients (41 males and 39 females) with a mean age of 35.4 (range 18 to 49). The mean BMI for the entire group was 26.6. The pre-operative, 6 month, 1 year, 2 year, and 3 year Modified Cin-cinatti Score in Group A (32 patients) was 54.4, 80.3, 82.7, 74.7 and 72.6. Similarly in Group B, the scores were 53, 41, 54, 56, 49.5 and in Group C the scores were 36.3, 36.3, 49.6, 36, and 35.7. The wound infection rate in Group A was 6.25%, in Group B was17.6% and Group C was 14.3%.

Conclusions: Initial results from this study suggest that BMI is an important predictor of outcome after chon-drocyte implantation. The group of patients that would gain most benefit from ACI are patients that are not overweight (defined by BMI in the range of 20 to 24.9). Further work is being carried out to support the hypothesis that surgeons should strongly consider not operating on patients unless the BMI is less than 25.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 391 - 391
1 Jul 2008
Krishnan S Skinner J Jagiello J Carrington R Flanagan A Briggs T Bentley G
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Aims: To investigate

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.

Patients and methods: 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). Biopsies of their cartilage repair site were stained with Haema-toxylin and Eosin and some with Safranin O and the neo-cartilage was graded as hyaline-like (n=32), mixed fibro-hyaline (n=19) and fibro-cartilagenous tissue (n=35). Macroscopic grading of the repair tissue using the international cartilage repair society grading system (ICRS) was available for fifty-six patients in this 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.

Results: The MCRS of all three histology groups were comparable at one year evaluation (p=0.34). However, their clinical scores at the latest follow-up showed a significantly superior result for those with hyaline-like repair tissue when compared to those with mixed fibro-hyaline and fibro-cartilagenous repair (p=0.05).

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).

Conclusion: We conclude that any form of cartilage repair gives good clinical outcome at one year. At four years and beyond, hyaline-like repair tissue produces a more favourable clinical outcome. Macroscopic evaluation using the ICRS grading system does not reflect the clinical outcome or its durability or the histological type of repair tissue.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 393 - 393
1 Jul 2008
Park D Krishnan S Skinner J Carrington R Flanagan A Briggs T Bentley G
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Purpose: We report on minimum 2 year follow-up results of 71 patients randomised to autologous chon-drocyte 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.

Introduction: 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 autolo-gous chondrocyte implantation (MACI) using a collagen bilayer seeded with chondrocytes.

Results: 71 patients with a mean age of 33 years (15–48) were randomised to undergo either an ACI-C or a MACI. 37 had ACI-C and 34 MACI. The mean size of the defect was 5.0cm2. Mean duration of symptoms was 104.4 months (9–456). Mean follow-up was 33.5 months (24–45). Functional assessment using the modified Cincinnati knee score, the Bentley functional rating score and the visual analogue score was carried out. Assessment using the modified Cincinnati knee score showed a good to excellent result in 57.1% of patients followed up at 2 years, and 65.2% at 3 years in the ACI-C group; and 63.6% of patients at 2 years, and 64% at 3 years in the MACI group. Arthroscopic assessments showed a good to excellent International Cartilage Repair Society score in 81.8% of ACI-C grafts (22 patients) and 50% of MACI grafts (6 patients). Fisher’s exact test showed a p value of p=0.35 (not statistically significant). Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in biopsies of 56.3% of the ACI-C grafts (9 out of 16 patients) and 30% of the MACI grafts (3 out of 10 patients) after 2 years. Fisher’s exact test showed a p value of p=0.25 (not statistically significant).

Conclusion: At this stage of the trial we conclude that the clinical, arthroscopic and histological outcomes are comparable for both ACI-C and MACI.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 323 - 324
1 Jul 2008
Krishnan S Skinner J Jagiello J Carrington R Flanagan A Briggs T Bentley G
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Aim: The aim of this study was to correlate the histology of cartilage repair site with long term clinical function.

Materials and methods: We have analyzed the clinical results of a cohort of patients who had collagen-covered autologous chondrocyte implantations performed since 1998. Our hypothesis was that the hyaline cartilage repair does influence the clinical outcome.

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).

Results: The clinical results showed that at one year, the percentage of patients with excellent and good results was 84.4, 89.5 and 74.3 respectively for those with hyaline, mixed fibro-hyaline and fibro-cartilagenous histology respectively. Their mean MCRS were 70.8, 72.4 and 66.2 respectively. This difference was not statistically significant (p=0.34).

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.

Conclusion: This study demonstrates that any form of cartilage repair would give good clinical outcome at one year. At four years and beyond, it appears that patients with hyaline repair tissue tend to show a more favourable clinical outcome whereas those who demonstrated mixed fibrohyaline and fibrocartilagenous repair would show less favourable clinical results.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 13 - 14
1 Mar 2008
Di Silvio L Ali Z Narvani A Goodship A Bentley G Tsiridis E
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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.

Conclusion: To date, no other study, to the author’s knowledge, has used MSCs and OP-1 together on a graft material; this funding, therefore, has very important clinical implications.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 14 - 14
1 Mar 2008
Tsiridis E Bhalla A Narvani A Goodship A Bentley G Di Silvio L
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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).

Conclusion: the osseoinductive potential of HA was markedly improved by the incorporation of MSC’s and OP-1. This type of graft could provide improved mechanical stability at an earlier time point, and may influence future clinical application of HA for load bearing sites.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 375 - 375
1 Oct 2006
Matthews S Gooding C Sood M Skinner J Bentley G
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Introduction: Autologous chondrocyte implantation (ACI) is a technique described for treating symptomatic osteochondral defects in the knee. It is contra-indicated, however, in a joint rendered unstable by a ruptured anterior cruciate ligament (ACL). We present our early experience of combined ACL and ACI repair.

Methods: Patients underwent arthroscopic examination and cartilage harvesting of the knee. Chondrocytes were then cultured in plasma and a second operation was undertaken approximately four weeks later to repair the ruptured ACL with hamstring graft and to implant the chondrocytes via formal arthrotomy. Patients then underwent a graduated rehabilitation program and were reviewed at 6 and 12 months. Functional measurements were made using the Bentley functional scale and the modified Cincinnati rating system, with pain measured on a visual analogue scale. All patients also underwent formal clinical examination at each review.

Results: 4 out of the 5 patients reported an improvement in pain as measured on visual analogue scale, with 1 patient reporting no difference. 4 patients had stable knees as determined by negative anterior draw, negative Lachman’s test and negative pivot shift test; one patient showed improvement, but remained pivot shift positive. Improvements in Bentley scores were noted in 3 patients. Cincinnati scores were markedly improved in 3 patients and slightly improved in the remaining 2 patients. The only operative complications were a traction neuropraxia to the saphenous nerve of one patient requiring no treatment and a manipulation under anaesthesia for poor mobilisation in another patient, which was successful in improving range of movement. A further patient required arthroscopic trimming of the cartilage graft which had overgrown; this was also successful.

Conclusion: Symptomatic cartilage defects and ACL deficiency may co-exist in many patients and represent a treatment challenge. Our early results suggest that a combined ACL and ACI repair is a viable option in this group of patients and should reduce the anaesthetic and operative risks of a two-stage repair. More patients and longer follow up will be required to fully assess this technique.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 403 - 403
1 Oct 2006
Krishnan SP Skinner JA Carrington RWJ Bentley G
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Introduction and aim: Several authors have suggested that hyaline repair tissue following autologous – chondrocyte implantation (ACI) gives better clinical results than either mixed hyaline and fibrocartilage or fibrocartilage alone. This data is based on the use of periosteum as a covering membrane in these previous studies. We have for some years been using a porcine collagen type 1/III membrane (ACI-C) instead of periosteum and have now the opportunity to analyze the clinical results when compared with the histology of the repaired defect. We have also analysed the influence on the result of age and sex of the patient, the etiology of the lesion, the duration of the knee symptoms, number of previous knee procedures, the site and size of defect and the preoperative functional scores.

Method: Until 2004, 234 patients underwent autologous chondrocyte implantation at our centre. The patients were assessed clinically by their modified Cincinnati scores prospectively from 1 to 4 years from surgery. Also at arthroscopy (1 to 3 years following ACI-C) they underwent biopsy of the implant where possible and the neo-cartilage was graded as hyaline (H), mixed fibrohyaline (F.H), fibrocartilagenous (F.C) and fibrous (F).

Results: The clinical results showed that older patients had poorer results (p< 0.001) and a high preoperative modified Cincinnati score predicted a good result (p< 0.001). Concerning the cause of the defect, the percentage of patients with excellent and good results were significantly low among those with previously failed ACIs and mosaicplaties (12.5%) compared with those following trauma, osteochondritis dessicans and chondromalacia patellae (67% to 77%). At 4 year follow-up, 75% of patients with hyaline neo-cartilage had excellent and good modified Cincinnati scores whereas those with mixed fibro-hyaline and fibro-cartilage had fewer excellent and good results (44.4% and 54.5% respectively). The other parameters such as gender, the site of defect, duration of knee symptoms and the number of previous procedures and the size of the defect did not significantly influence the outcome. In conclusion, patients most likely to benefit from autologous chondrocyte implantation using a collagen membrane (ACI – C) are younger patients with higher preoperative functional scores and those who develop hyaline neo-cartilage.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 379 - 379
1 Oct 2006
Anand A Akmal M Wiseman M Goodship A Bentley G
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Study Purpose: The cause of intervertebral disc degeneration (IVDD) is multifactorial. One proposed mechanism is that IVDD originates in the nucleus pulposus (NP) and progresses radially to the annulus fibrosis (AF). Failure of current treatment modalities in preventing and treating IVDD and thereby low back pain have led to a growing interest in tissue-engineered solutions where a biological repair is induced. By preventing the abnormality at the NP it may be possible to halt further progression of IVDD. Injection of NP cells into an early degenerative IVD, where the AF is still intact, may retard the degenerative process and is presently under investigation. Using a three-dimensional scaffold that could be successfully introduced into the NP cavity through minimally invasive techniques would prevent the loss of chondrocytic phenotype of the cells and be an improvement over the existing technique by which cells are directly injected into the NP cavity.

Methods: (1) CaSO4 and CaCO3 alginates were injected into the NP cavity of a bovine tail. After 90 minutes the tail was dissected to reveal the gel. (2) NP cells released from pooled bovine NP tissue were dispersed into the CaSO4 and CaCO3 alginate gels (10x106 cells.mL-1) with and without Synvisc® and cultured for 21 days.

Results: (1) Injectable alginate suspensions formed solid viscoelastic gels, filling the exact shape of the NP cavity. (2) NP DNA and ECM synthesis was significantly greater in the CaCO3 alginate gel than in the CaSO4 alginate gel (p< 0.05). (3) Synvisc® significantly increased sulphated GAG (p< 0.01) and collagen (p< 0.05) production. These effects were supported histologically and immunohistologically where cells in the CaCO3 and Synvisc® gels stained more intensely for proteoglycan and collagen type II.

Conclusions: Both CaCO3 alginate gel and CaSO4 alginate gel are injectable and are capable of sustaining NP cells in-vitro. Cells remain viable, maintain their phenotype, proliferate and produce ECM during the culture period. The CaCO3 alginate gel provides a three-dimensional matrix more favourable to NP cellular activity than the CaSO4 alginate gel. Synvisc® behaves as a chondro-stimulant significantly enhancing NP cell metabolic activity. This study demonstrates a successful tissue-engineered approach for replacing the NP and, subject to further studies, may be used for retarding mild-to-moderate IVDD, alleviating lower back pain and restoring a functional NP through a minimally invasive technique.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 261 - 261
1 May 2006
Baco A Bentley G Alyawer H
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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.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 254 - 254
1 May 2006
Derrett S Stokes E James M Bartlett W Bentley G
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Purpose: To assess costs and health status outcomes following ACI and mosaicplasty used to treat chondral knee defects (1).

Methods: Patients received ACI or mosaicplasty at the Royal National Orthopaedic Hospital between 1997 and 2001, or, were on a waiting list for ACI. Resource use per patient was collected to two years post-operatively. A postal questionnaire collected sociodemographic characteristics, knee-related (Modified Cincinnati Knee Rating System) and general health status (EQ-5D).

Results: 53 ACI, 20 mosaicplasty and 22 patients waiting for ACI participated in this study. The average cost per patient was higher for ACI (£10,600: 95%CI £10,036-£11,214) than for mosaicplasty (£7,948: 95%CI £6,957-£9,243). Estimated average EQ-5D social tariff improvements for QALYs (quality adjusted life years) were 0.23 for ACI and 0.06 for mosaicplasty. Average costs per QALY were: £23,043 for ACI and £66,233 for mosaicplasty. The ICER (incremental cost effectiveness ratio) for providing ACI over mosaicplasty was £16,349. Post-operatively, ACI and mosaicplasty patients (combined) experienced better health status than patients waiting for ACI. ACI patients tended to have better health status outcomes than mosaicplasty patients, although this was not statistically significant.

Conclusions: Average costs were higher for ACI than for mosaicplasty. However, both the estimated cost per QALY and ICER fell beneath an implicit English funding threshold of £30,000 per QALY. To our knowledge this is the first study to compare the costs and utility of ACI with alternative ‘best’ treatments for people with chondral knee problems. Prospective studies are required to confirm these results.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 114 - 114
1 Mar 2006
Bartlett W Gooding C Amin A Skinner J Carrington R Flanagan A Briggs T Bentley G
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Background: Autologous chondrocyte implantation (ACI) was introduced over 15 years ago as a treatment for full-thickness chondral defects in the knee. Current understanding of ACI graft morphology and maturation in humans is limited. The aims of this study were determine the incidence of hyaline-like repair following ACI, and to clarify the relationship between repair morphology and clinical outcome.

Methods: A retrospective review of 194 ACI graft biopsies from 180 patients, and their clinical outcome was conducted. 154 Biopsies were performed 1 year after implantation and 40 biopsies were performed at 2 years. Three techniques of ACI implantation were used; Collagen covered ACI (ACI-C), periosteum covered ACI (ACI-P) and Matrix-Induced ACI (MACI).

Results: At 1 year, hyaline repair tissue was found in 48 (53%) ACI-C grafts, 7 (44%) ACI-P grafts, and 12 (36%) MACI grafts. The frequency of hyaline tissue found in biopsies performed at 2 years (84%) was significantly higher than those performed at 1 year (48.6%), p=0.0001, suggesting that grafts continue to remodel after the first year post implantation.

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.

Conclusions: Achieving hyaline-like repair is critical to the longevity of cartilage repair. The finding of hyaline-like cartilage or fibrohyaline cartilage in 31 of 37 biopsies (84%) performed after 2 years is therefore encouraging and supports further use of the ACI technique.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 114 - 114
1 Mar 2006
Bartlett W Gooding C Skinner J Carrington R Flanagan A Briggs T Bentley G
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Background: Autologous Chondrocyte Implantation (ACI) is widely used 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/III collagen as a cover (ACI-C), and the use of a collagen bilayer seeded with chondrocytes (MACI).

Aim: To determine whether differences in clinical, arthroscopic and histological outcomes at 1 year exist between ACI-C and MACI techniques.

Methods: We have performed a prospective randomised comparison of ACI-C versus MACI for the treatment of symptomatic chondral defects of the knee on 91 patients of whom 44 received ACI-C and 47 received MACI grafts.

Results: Both treatments resulted in improvements of clinical scores after 1 year. Mean modified Cincinnati knee scores increased by 17.5 in the ACI-C group and 19.6 in the MACI group (p> 0.05). Arthroscopic assessments performed after 1 year demonstrated good to excellent ICRS graft repair scores in 79% of ACI-C grafts and 67% of MACI grafts. Hyaline-like or hyaline-like cartilage with fibrocartilage was found in the biopsies of 43% of ACI-C grafts and 36% of MACI grafts after 1 year. The rate of graft hypertrophy was 9% in the ACI-C group and 6% in the MACI group. The frequency of re-operation was 9% in each group.

Conclusions: We conclude that clinical, arthroscopic and histological outcomes are comparable for both ACI-C and MACI techniques. While the MACI technique is technically attractive, further long-term studies are required before widespread adoption of this new technique.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 322 - 322
1 Sep 2005
Gooding C Bentley G Carrington R Briggs T Skinner J
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Introduction and Aims: ACI (autologous chondrocyte implantation) using a periosteum cover was developed by Peterson et al. Recently, the technique has been developed using a Type I/Type III collagen membrane (Chondro-Gide). A second technique MACI (matrix-induced autologous chondrocyte implantation) has evolved using a membrane with chondrocytes seeded onto its surface. Aim is to review the one and two-year results of the first 159 patients at a single regional centre.

Method: The two-stage procedure was performed with a standardised, progressive rehabilitation program. Patients were assessed clinically at three, six, nine, 12 and 24 months (pain score, Modified Cincinnati, Bentley), and arthroscopically at 12 and 24 months.

Results: 159 patients have been assessed at one year and 101 patients at two years. Of those patients reviewed at one year, 110 patients had the ACI repair with Chondro-Gide, 31 patients had the ACI repair with periosteum and 18 patients had the MACI repair. Sixty-nine percent had good or excellent results at one year and 60% at two years.

These figures represent the early results of this study performed at this unit.

Conclusion: We propose that the ACI technique is valuable for selected patients with Chondral and osteochondral defects of the knee even with large and multiple defects in the articular cartilage.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 344 - 345
1 Sep 2005
Beard D Bentley G Carrington R Briggs T Skinner J
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Introduction and Aims: Uni-compartmental knee arthroplasty (UKA) is appropriate for one in three osteoarthritic knees requiring replacement. An accelerated protocol enables patients undergoing UKA to be discharged within 24 hours of surgery. Before such an approach is universally accepted it must be safe, effective and economically viable. A study was performed to compare the new accelerated protocol with current standard care in a state healthcare system.

Method: A single blind RCT design was used. Patients eligible for UKA were screened for NSAID tolerance, social circumstances and geographical location before allocation to either an accelerated recovery group (Group A) or a standard non-accelerated group (Group S). The accelerated protocol included dedicated pain management and discharge support. Primary outcome was the Oxford Knee Assessment at six months post-operation, compared using independent t tests. Pain, range of movement and incidence of complications were also recorded by assessors blind to group allocation. Cost effectiveness was calculated in quality life adjusted years (QLAY) using the Euroqual instrument. The study power was sufficient to avoid type 2 errors. The study was supported by a NHS Regional R& D grant.

Results: Forty-one patients (21 group A, 20 group S) were included. Groups had comparable age and patient profiles. Average discharge time was 37 hours (1.5 days) for group A and 114 hours (4.3 days) for group S. Pain on hospital discharge was similar for both groups. No significant difference was found between groups for pain or range of movement at any time, although patients in group S regained pre-operative flexion faster than group A. One major complication occurred in each group; one infection (group S) and one manipulation for poor movement (group A). The cost per QLAY for the new protocol was 59% of the standard care.

Conclusion: The new protocol allows for safe accelerated discharge from hospital after UKA. The approach is cost-effective and should help to increase the throughput of patients who require knee replacement.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 263 - 263
1 Mar 2004
Carrington R Skinner J Lewis A Bentley G
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Aims: The objective of this study was to clinically assess the outcome of CADCAM femoral components in the revision hip replacement. Methods: Between 1991 and 2000, 125 revision total hip replacements using CAD-CAM femoral components were performed. Clinical assessment was performed using the Harris Hip score, by direct patient consultation, and telephone or postal questionnaire. Survivorship was defined as the requirement for revision. Results: The patients were reviewed at a mean of 5.2 yrs (1 to 10)

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. Conclusions: CAD-CAM technology provides a viable alternative to the challenge of revision hip surgery, with results comparable to other cementless techniques.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 107 - 107
1 Feb 2003
Biant LC Bentley G
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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.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 105 - 105
1 Feb 2003
Bentley G Biant LC Hunter M Nicolau M Carrington R Williams A Goldberg A Akmal M Pringle J
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Mosaicplasty1 and Autologous Chondrocyte Implantation2 (ACI) are both modern cartilage repair techniques used to repair symptomatic articular cartilage defects in the knee, based on small osteochondral grafts and cultured chondrocytes respectively. The aim is the restoration of articular cartilage, but until now there is no data comparing the two methods.

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.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 106 - 106
1 Feb 2003
Bentley G Hunter M Biant LC Nicolau M Carrington R Williams A Goldberg A Akmal M Pringle J
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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.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 118 - 118
1 Feb 2003
Biring GS Bentley G
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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.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 5 - 5
1 Jan 2003
Singh A Akmal M Enobakhare B Kesani A Goodship A Bentley G
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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 tissue1 and is available commercially for the intra-articular injective treatment of osteoarthritis of the knee and periarthritis of the shoulder. Although it is known to improve intra-articular lubrication it is also thought to promote articular cartilage structure and prevent catabolism of matrix proteoglycans in osteoarthritis. Clinical studies have shown beneficial effects lasting for many months after cessation of therapy unlike anti-inflammatory drugs that have relatively short term relieving effects2,3 . Documentation of the true chondroprotective effects of hyaluronic acid (HA) at the cellular level is lacking and therefore this study aimed to identify the effects of HA on chondrocytes cultured in vitro.

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.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 5 - 5
1 Jan 2003
Mannering N Akmal M Enobakhare B Singh A Goodship A Bentley G
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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 synthesis1. However it has also been suggested that the beneficial effects in vivo may be due to prevention of inflamed synovium causing cartilage degradation2. Our aim was to assess the effect of a commercially available preparation of methylprednisolone (MP), at clinical doses, on articular chondrocytes cultured in vitro.

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.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 6 - 6
1 Jan 2003
Kesani A Akmal M Enobakhare B Mannering N Goodship A Bentley G
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Nicotine is a constituent of tobacco smoke and is present in the body fluids of smokers1,2. Numerous studies have confirmed that smoking is a strong risk factor for back pain3. The most widely accepted explanation for the association is that smoking leads to malnutrition of spinal discs due to carboxyhaemoglobin formation. However, other constituents of smoke, such as nicotine, may also be responsible for intervertebral disc (IVD) degeneration by leading to cell necrosis in both the nucleus pulposus and annulus fibrosis. Despite evidence suggesting the detrimental effect on a variety of tissues, the effect of nicotine on IVD cells has not previously been investigated. This study investigated the influence of nicotine on the metabolism and viability of IVD cells cultured in vitro.

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.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 2 - 3
1 Jan 2003
Akmal M Kesani A Kakar S Bentley G
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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 1,2. In wound infections, peritonitis and some other conditions pH is used as an indicator of infection in clinical practice3. The aim was to assess whether fluid biochemistry (pH, pCO2, pO2, Lactate and Glucose) is altered in infected total knee replacements and whether it could be used as a diagnostic test.

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.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 242 - 242
1 Nov 2002
Bentley G Goldberg A Biant L Hunter M Carrington R
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Many methods have been described over the past 5 years for repair of articular cartilage defects. The best reported results have been from the use of autologous chondrocyte transplantation (ACT)(1) and mosaicplasty.(2) There have, however, been no prospective clinical trials of these two methods. In this trial 70 patients were prospectively randomized to receive either autologous chondrocyte transplantation (37) or mosaicplasty (33) in the knee. 37 patients were female and 33 male. The average age was 32 years (16 – 44). The indications for surgery were persistent pain and mechanical symptoms in the knee with an isolated defect of the articular cartilage. 38 (56%) were post-traumatic, 12 (16%) due to osteochondritis dissecans, 10 (14%) due to previous meniscectomy, and 10 (14%) due to chondromalacia patellae. The size of the defects ranged from 2cm2 to 12cm2 (mean 4.8cm2). There were 35 defects on the medial femoral condyle, 13 on the lateral femoral condyle, 17 on the patella and 5 on the trochlear. 31 patients were undergoing primary surgery and 39 secondary surgery. All were independently reviewed using the Visual Analogue Pain Score, the Cincinatti Pain Score and the Stanmore Score. Patients were arthroscoped at one year with MRI scan and biopsies where possible.

Results: The visual analogue pain score improved overall from a mean of 5.4 (range 3.4 – 7.4) pre-operatively to 3.9 (1.8 – 5.1) at one year review. Similarly the Cincinatti pain score improved from 6.5 pre-operatively to 10.2 post-operatively and the Cincinatti function score improved from 46 to 62 at one year before sport commenced. Overall 71% (49) patients were excellent or good on the clinical scoring scales, 15% (11) were fair, and 14% (10) were poor. The 10 poor results were no different from the main group with regard to age, sex, pain level or site or size of lesion. However, 5 were secondary procedures, 2 had multiple lesions, and 3 had had previous ruptured anterior cruciate ligaments. Arthroscopy and biopsy of 21 lesions so far after one year has shown mature articular cartilage in 2, and immature cartilage in 19. In all cases there was bonding of the repair tissue to the underlying bone. This study is already clarifying the role of ACT and mosaicplasty in the management of cartilage defects in the knee and also the necessity for the use of periosteal covering membrane.


The purpose of this study was to evaluate the influence of trochlear design in total knee replacement with and without patellar resurfacing.

Methods and Results: In 1992 a trial was set up, including all patients undergoing primary PFC (Johnson & Johnson) total knee replacement. Patients were randomised to either patellar resurfacing or retention. The patients were assessed using the American Knee Society rating, a clinical anterior knee pain score and BOA patient satisfaction score. Assessment was performed without knowing whether the patella had been resurfaced.

In July 1998 we began using the PFC Sigma. This incorporates a deeper trochlear groove with a 5° valgus angle.

We compared the results for the two types of prosthesis. In the PFC group there were 474 knees in 390 patients. Follow-up was from 2 to 9 years (mean 5.5 years). The overall prevalence of anterior knee pain) was 25.1% (58 knees) and 5.3% (13 knees) in the non-resurfaced group (n=231) versus the resurfaced group (n=243) respectively. Anterior knee pain became apparent in all cases within 18 months.

In the PFC sigma group there were 67 knees in 62 patients. Follow-up was from 18 months to 3 years (mean 2 years). The incidence of anterior knee pain was 0 in the resurfaced group (n=30) versus 37.8% (14 knees) in the non-resurfaced group (n=37). Knee scores were lower in the non-resurfaced groups for each prosthesis.

Conclusion: The prevalence of anterior knee pain was significantly higher in knees with non-resurfacing of the patella. The asymmetrical, deeper femoral groove improves anterior knee pain with the resurfaced patella but may contribute to it if not resurfaced. We recommend patellar resurfacing in all cases where technically possible.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 125 - 125
1 Jul 2002
Maruthainar N Graham D Surace F Bentley G
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The issue of preservation or sacrifice of the posterior cruciate ligament in total knee arthroplasty remains unresolved.

We report the results of 200 consecutive total knee arthroplasties performed at our hospital under the direction of the senior author. Pre-operatively, patients were randomly chosen to receive either a Kinemax (posterior cruciate retaining) or a Press-Fit-Condylar (posterior cruciate sacrificing) prosthesis. We implanted 97 Kinemax and 103 Press-Fit-Condylar prostheses which were prospectively followed-up by clinical and radiographic assessment. Review at mean follow-up of 2.7 years showed a satisfactory clinical result in both groups [Surace, et al., 1994].

We present the results of our further review, with maximum follow-up of over nine years (mean: 5.9 years). Revision of the implant has been performed in five knees (three Kinemax and two Press-Fit-Condylar). The polythene spacer had to be replaced in one patient with a Press-Fit-Condylar implant.

Patients were assessed with the Hospital for Special Surgery Knee Score and radiologically assessed with the Knee Society Roentgenographic Evaluation and Scoring System. Pre-operative demographics and disease states of the patients were similar, with an average Hospital for Special Surgery Knee Score of 63. At the latest assessment the average knee score was good (85). Remarkably, the mean knee score for the posterior cruciate sacrifice and the PCL groups remains similar (mean: 85). Radiographic evaluation demonstrated that the prosthetic components of both groups were in comparable alignment. The posterior cruciate ligament retained (Kinemax) patient group showed a mean 5.9 degrees of the valgus angle at the knee. The angle in the posterior cruciate ligament sacrifice (PFC implant) group was 6.2 degrees. Evaluation of the radiolucent depths below the femoral, tibial and any patella component showed a mean total depth of 1.5 mm (pcl retaining) and 1.7 mm (pcl sacrificing).

Our study presents a quantitative perspective of the results of total knee replacement with proven implant systems and performed in a general orthopaedic unit by both consultants and surgeons in training. The Kinemax (Howmedica) and Press-Fit-Condylar (DePuy Johnson and Johnson) implant systems have both previously demonstrated good results and continue to be available with little subsequent modification.

To our knowledge, there have been no other large prospectively randomised studies of posterior cruciate ligament preservation or sacrifice in total knee replacement.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 119 - 119
1 Jul 2002
Davidson A Bentley G
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We clinically and radiologically reviewed 79 uncemented PFC acetabular components inserted by our unit during a seven-year period, June 1991 to June 1998. Of these, 50 (63.3%) were primary and 29 (26.7%) were revision arthroplasties. The mean follow-up was five years (60 months), with a range of 12 to 95 months. Sixteen (20%) were excluded from the study, leaving 63 (26.7%) for review. Three (4.7%) cases were deemed to have failed (at 63, 69, 79 months), all of which were primary arthroplasties. One of them was found to be loose at revision and the other two cups had 2 mm of periacetabular radiolucency in only one zone, but had no definite evidence of loosening.

The remaining 60 (95.3%) cases showed no radiological evidence of migration of any cups, and no hip had a radiolucent line in all three zones of the acetabulum. Clinical review gave a mean Harris hip score of 96.5. Fifty (79.4%) reported no pain from the hip. One case (1.6%) had undergone recent revision of the stem, at which time the cup was found to be stable. Three (4.7%) reported slight, occasional pain. Another three (4.7%) described mild pain that did not compromise their average activities and was relieved by simple analgesia. Two cases (3.2%) complained of moderate pain that placed some limitations on their activities and required regular analgesia, and one elderly patient who had an ankylosed contralateral hip and ipsilateral sciatic nerve palsy described marked pain (1.6%), and these were considered poor outcomes. In all of these cases the cups were clinically and radiologically stable.

In conclusion, 81% of outcomes were excellent, painfree THRs. A further 4.75% had good and 4.75% fair results. 4.75% had poor outcomes and 4.75% of cases failed. We conclude that the PFC cup merits continued use and follow-up, and together with other uncemented cup designs, may produce benefits in the form of quality and longevity of results in total hip arthroplasty.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 157 - 157
1 Jul 2002
Waters T Bentley G
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The purpose of this study was to evaluate the role of patellar resurfacing in total knee replacement surgery. We reviewed 48 patients who had undergone bilateral knee replacement with patellar resurfacing on only one side. Follow-up was from 18 months to 9.5 years and the patients were assessed using the Knee Society rating, a clinical anterior knee pain score and BOA patient 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.

52.1% of patients favoured the resurfaced knee, 8% the unresurfaced knee and 39.9% had no particular preference. The overall prevalence of anterior knee pain was 8.3% in the resurfaced cases (3 mild, 1 moderate) and 27.1% in the unresurfaced knees (8 mild, 3 moderate, 2 severe). No significant difference was found between knee scores.

This study shows a significantly higher rate of anterior knee pain in unresurfaced patellae and preference for the resurfaced side.