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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.


The Bone & Joint Journal
Vol. 103-B, Issue 7 | Pages 1325 - 1325
1 Jul 2021
Bentley G


The Bone & Joint Journal
Vol. 96-B, Issue 1 | Pages 54 - 58
1 Jan 2014
Vijayan S Bentley G Rahman J Briggs TWR Skinner JA Carrington RWJ

The management of failed autologous chondrocyte implantation (ACI) and matrix-assisted autologous chondrocyte implantation (MACI) for the treatment of symptomatic osteochondral defects in the knee represents a major challenge. Patients are young, active and usually unsuitable for prosthetic replacement. This study reports the results in patients who underwent revision cartilage transplantation of their original ACI/MACI graft for clinical or graft-related failure. We assessed 22 patients (12 men and 10 women) with a mean age of 37.4 years (18 to 48) at a mean of 5.4 years (1.3 to 10.9). The mean period between primary and revision grafting was 46.1 months (7 to 89). The mean defect size was 446.6 mm2 (150 to 875) and they were located on 11 medial and two lateral femoral condyles, eight patellae and one trochlea.

The mean modified Cincinnati knee score improved from 40.5 (16 to 77) pre-operatively to 64.9 (8 to 94) at their most recent review (p < 0.001). The visual analogue pain score improved from 6.1 (3 to 9) to 4.7 (0 to 10) (p = 0.042). A total of 14 patients (63%) reported an ‘excellent’ (n = 6) or ‘good’ (n = 8) clinical outcome, 5 ‘fair’ and one ‘poor’ outcome. Two patients underwent patellofemoral joint replacement. This study demonstrates that revision cartilage transplantation after primary ACI and MACI can yield acceptable functional results and continue to preserve the joint.

Cite this article: Bone Joint J 2014;96-B:54–8.


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 10 | Pages 1377 - 1381
1 Oct 2012
Jaiswal PK Bentley G Carrington RWJ Skinner JA Briggs TWR

We analysed whether a high body mass index (BMI) had a deleterious effect on outcome following autologous chondrocyte implantation (ACI) or matrix-carried autologous chondrocyte implantation (MACI) for the treatment of full-thickness chondral defects of the knee from a subset of patients enrolled in the ACI vs MACI trial at The Royal National Orthopaedic Hospital.

The mean Modified Cincinnati scores (MCS) were significantly higher (p < 0.001) post-operatively in patients who had an ideal body weight (n = 53; 20 to 24.9 kg/m2) than in overweight (n = 63; 25 to 30 kg/m2) and obese patients (n = 22; > 30 kg/m2). At a follow-up of two years, obese patients demonstrated no sustained improvement in the MCS. Patients with an ideal weight experienced significant improvements as early as six months after surgery (p = 0.007). In total, 82% of patients (31 of 38) in the ideal group had a good or excellent result, compared with 49% (22 of 45) of the overweight and 5.5% (one of 18) in the obese group (p < 0.001). There was a significant negative relationship between BMI and the MCS 24 months after surgery (r = -0.4, p = 0.001).

This study demonstrates that obese patients have worse knee function before surgery and experience no sustained benefit from ACI or MACI at two years after surgery. There was a correlation between increasing BMI and a lower MCS according to a linear regression analysis. On the basis of our findings patient selection can be more appropriately targeted.


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 4 | Pages 504 - 509
1 Apr 2012
Bentley G Biant LC Vijayan S Macmull S Skinner JA Carrington RWJ

Autologous chondrocyte implantation (ACI) and mosaicplasty are methods of treating symptomatic articular cartilage defects in the knee. This study represents the first long-term randomised comparison of the two techniques in 100 patients at a minimum follow-up of ten years. The mean age of the patients at the time of surgery was 31.3 years (16 to 49); the mean duration of symptoms pre-operatively was 7.2 years (9 months to 20 years). The lesions were large with the mean size for the ACI group being 440.9 mm2 (100 to 1050) and the mosaicplasty group being 399.6 mm2 (100 to 2000). Patients had a mean of 1.5 previous operations (0 to 4) to the articular cartilage defect. Patients were assessed using the modified Cincinnati knee score and the Stanmore-Bentley Functional Rating system. The number of patients whose repair had failed at ten years was ten of 58 (17%) in the ACI group and 23 of 42 (55%) in the mosaicplasty group (p < 0.001).

The functional outcome of those patients with a surviving graft was significantly better in patients who underwent ACI compared with mosaicplasty (p = 0.02).


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 4 | Pages 488 - 492
1 Apr 2012
Vijayan S Bartlett W Bentley G Carrington RWJ Skinner JA Pollock RC Alorjani M Briggs TWR

Matrix-induced autologous chondrocyte implantation (MACI) is an established technique used to treat osteochondral lesions in the knee. For larger osteochondral lesions (> 5 cm2) deeper than approximately 8 mm we have combined the use of two MACI membranes with impaction grafting of the subchondral bone. We report our results of 14 patients who underwent the ‘bilayer collagen membrane’ technique (BCMT) with a mean follow-up of 5.2 years (2 to 8). There were 12 men and two women with a mean age of 23.6 years (16 to 40). The mean size of the defect was 7.2 cm2 (5.2 to 12 cm2) and were located on the medial (ten) or lateral (four) femoral condyles. The mean modified Cincinnati knee score improved from 45.1 (22 to 70) pre-operatively to 82.8 (34 to 98) at the most recent review (p < 0.05). The visual analogue pain score improved from 7.3 (4 to 10) to 1.7 (0 to 6) (p < 0.05). Twelve patients were considered to have a good or excellent clinical outcome. One graft failed at six years.

The BCMT resulted in excellent functional results and durable repair of large and deep osteochondral lesions without a high incidence of graft-related complications.


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 1 | Pages 141 - 142
1 Jan 2012
Bentley G Kenwright J

None


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 6 | Pages 903 - 903
1 Jun 2010
Bentley G


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).


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 12 | Pages 1575 - 1578
1 Dec 2009
Jaiswal PK Macmull S Bentley G Carrington RWJ Skinner JA Briggs TWR

Smoking is known to have an adverse effect on wound healing and musculoskeletal conditions. This case-controlled study looked at whether smoking has a deleterious effect in the outcome of autologous chondrocyte implantation for the treatment of full thickness chondral defects of the knee.

The mean Modified Cincinatti Knee score was statistically significantly lower in smokers (n = 48) than in non-smokers (n = 66) both before and after surgery (p < 0.05). Smokers experienced significantly less improvement in the knee score two years after surgery (p < 0.05). Graft failures were only seen in smokers (p = 0.016). There was a strong negative correlation between the number of cigarettes smoked and the outcome following surgery (Pearson’s correlation coefficient −0.65, p = 0.004).

These results suggest that patients who smoke have worse pre-operative function and obtain less benefit from this procedure than non-smokers. The counselling of patients undergoing autologous chondrocyte implantation should include smoking, not only as a general cardiopulmonary risk but also because poorer results can be expected in smokers following this procedure.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 9 | Pages 1172 - 1177
1 Sep 2009
Gikas PD Morris T Carrington R Skinner J Bentley G Briggs T

Autologous chondrocyte implantation is an option in the treatment of full-thickness chondral or osteochondral injuries which are symptomatic. The goal of surgery and rehabilitation is the replacement of damaged cartilage with hyaline or hyaline-like cartilage, producing improved levels of function and preventing early osteoarthritis. The intermediate results have been promising in terms of functional and clinical improvement.

Our aim was to explore the hypothesis that the histological quality of the repair tissue formed after autologous chondrocyte implantation improved with increasing time after implantation.

In all, 248 patients who had undergone autologous chondrocyte implantation had biopsies taken of the repair tissue which then underwent histological grading. Statistical analysis suggested that with doubling of the time after implantation the likelihood of a favourable histological outcome was increased by more than fourfold (p < 0.001).


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 8 | Pages 997 - 1006
1 Aug 2009
Gikas PD Bayliss L Bentley G Briggs TWR

Chondral damage to the knee is common and, if left untreated, can proceed to degenerative osteoarthritis. In symptomatic patients established methods of management rely on the formation of fibrocartilage which has poor resistance to shear forces. The formation of hyaline or hyaline-like cartilage may be induced by implanting autologous, cultured chondrocytes into the chondral or osteochondral defect.

Autologous chondrocyte implantation may be used for full-thickness chondral or osteochondral injuries which are painful and debilitating with the aim of replacing damaged cartilage with hyaline or hyaline-like cartilage, leading to improved function. The intermediate and long-term functional and clinical results are promising.

We provide a review of autologous chondrocyte implantation and describe our experience with the technique at our institution with a mean follow-up of 32 months (1 to 9 years).

The procedure is shown to offer statistically significant improvement with advantages over other methods of management of chondral defects.


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 8 | Pages 1110 - 1114
1 Aug 2007
Biant LC Bentley G

Implantation of autologous chondrocytes and matrix autologous chondrocytes are techniques of cartilage repair used in the young adult knee which require harvesting of healthy cartilage and which may cause iatrogenic damage to the joint. This study explores alternative sources of autologous cells.

Chondrocytes obtained from autologous bone-marrow-derived cells and those from the damaged cartilage within the lesion itself are shown to be viable alternatives to harvest-derived cells. A sufficient number and quality of cells were obtained by the new techniques and may be suitable for autologous chondrocyte and matrix autologous chondrocyte implantation.


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 5 | Pages 696 - 697
1 May 2006
Bentley G Dickson R


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 4 | Pages 544 - 553
1 Apr 2006
Akmal M Anand A Anand B Wiseman M Goodship AE Bentley G

Bovine and human articular chondrocytes were seeded in 2% alginate constructs and cultured for up to 19 days in a rotating-wall-vessel (RWV) and under static conditions. Culture within the RWV enhanced DNA levels for bovine chondrocyte-seeded constructs when compared with static conditions but did not produce enhancement for human cells. There was a significant enhancement of glycosaminoglycans and hydroxyproline synthesis for both bovine and human chondrocytes. In all cases, histological analysis revealed enhanced Safranin-O staining in the peripheral regions of the constructs compared with the central region. There was an overall increase in staining intensity after culture within the RWV compared with static conditions. Type-II collagen was produced by both bovine and human chondrocytes in the peripheral and central regions of the constructs and the staining intensity was enhanced by culture within the RWV. A capsule of flattened cells containing type-I collagen developed around the constructs maintained under static conditions when seeded with either bovine or human chondrocytes, but not when cultured within the RWV bioreactor.