Autologous chondrocyte implantation is a NICE approved intervention however it involves the morbidity of two operations, a prolonged rehabilitation and substantial healthcare costs. This study describes a novel, one-step, bone marrow (BM) derived mesenchymal stem cell (MSC) transplantation technique for treating knee osteochondral lesions and presents our prospective clinical study investigating the success of this technique in 206 lesions over a 5 year period. The surgical technique involves harvesting BM from patients’ anterior superior iliac spines, centrifugation to isolate MSCs and seeding into a type 1 collagen scaffold (SyngenitTM Biomatrix). Autologous fibrin glue is used to secure the scaffold into the defect. Inclusion criteria included patients aged 15 – 55 years old with symptomatic osteochondral lesions >1cm2. Exclusion criteria included patients with ligament instability, uncorrected alignment, inflammatory arthropathy and a Body Mass Index >35 kg/m2. Outcome measures included the Modified Cincinnati Knee Rating System (MCKRS), complications and reoperations.Abstract
Background
Methodology
The 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:
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.
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).
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.
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.
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).
We prospectively studied the clinical, arthroscopic and histological results of collagen-covered autologous chondrocyte implantation (ACI-C) in patients with symptomatic osteochondritis dissecans of the knee. The study included 37 patients who were evaluated at a mean follow-up of 4.08 years. Clinical results showed a mean improvement in the modified Cincinnati score from 46.1 to 68.4. Excellent and good clinical results were seen in 82.1% of those with juvenile-onset osteochondritis dissecans but in only 44.4% of those with adult-onset disease. Arthroscopy at one year revealed International Cartilage Repair Society grades of 1 or 2 in 21 of 24 patients (87.5%). Of 23 biopsies, 11 (47.8%) showed either a hyaline-like or a mixture of hyaline-like and fibrocartilage, 12 (52.2%) showed fibrocartilage. The age at the time of ACI-C determined the clinical outcome for juvenile-onset disease (p = 0.05), whereas the size of the defect was the major determinant of outcome in adult-onset disease (p = 0.01).
We investigated the prognostic indicators for collagen-covered autologous chondrocyte implantation (ACI-C) performed for symptomatic osteochondral defects of the knee. We analysed prospectively 199 patients for up to four years after surgery using the modified Cincinnati score. Arthroscopic assessment and biopsy of the neocartilage was also performed whenever possible. The favourable factors for ACI-C include younger patients with higher pre-operative modified Cincinnati scores, a less than two-year history of symptoms, a single defect, a defect on the trochlea or lateral femoral condyle and patients with fewer than two previous procedures on the index knee. Revision ACI-C in patients with previous ACI and mosaicplasties which had failed produced significantly inferior clinical results. Gender (p = 0.20) and the size of the defect (p = 0.97) did not significantly influence the outcome.
Autologous chondrocyte implantation (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 have performed a prospective, randomised comparison of ACI-C and MACI for the treatment of symptomatic chondral defects of the knee in 91 patients, of whom 44 received ACI-C and 47 MACI grafts. Both treatments resulted in improvement of the clinical score after one year. The mean modified Cincinnati knee score increased by 17.6 in the ACI-C group and 19.6 in the MACI group (p = 0.32). Arthroscopic assessments performed after one year showed a good to excellent International Cartilage Repair Society score in 79.2% of ACI-C and 66.6% of MACI grafts. Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in the biopsies of 43.9% of the ACI-C and 36.4% of the MACI grafts after one year. The rate of hypertrophy of the graft was 9% (4 of 44) in the ACI-C group and 6% (3 of 47) in the MACI group. The frequency of re-operation was 9% in each group. We conclude that the clinical, arthroscopic and histological outcomes are comparable for both ACI-C and MACI. While MACI is technically attractive, further long-term studies are required before the technique is widely adopted.
Autologous chondrocyte implantation (ACI) is a technique used for the treatment of symptomatic osteochondral defects of the knee. A variation of the original periosteum membrane technique is the matrix-induced autologous chondrocyte implantation (MACI) technique. The MACI membrane consists of a porcine type-I/III collagen bilayer seeded with chondrocytes. Osteochondral defects deeper than 8 to 10 mm usually require bone grafting either before or at the time of transplantation of cartilage. We have used a variation of Peterson’s ACI-periosteum sandwich technique using two MACI membranes with bone graft which avoids periosteal harvesting. The procedure is suture-free and requires less operating time and surgical exposure. We performed this MACI-sandwich technique on eight patients, five of whom were assessed at six months and one year post-operatively using the modified Cincinnati knee, the Stanmore functional rating and the visual analogue pain scores. All patients improved within six months with further improvement at one year. The clinical outcome was good or excellent in four after six months and one year. No significant graft-associated complications were observed. Our early results of the MACI-sandwich technique are encouraging although larger medium-term studies are required before there is widespread adoption of the technique.
Autologous chondrocyte implantation (ACI) and mosaicplasty are both claimed to be successful for the repair of defects of the articular cartilage of the knee but there has been no comparative study of the two methods. A total of 100 patients with a mean age of 31.3 years (16 to 49) and with a symptomatic lesion of the articular cartilage in the knee which was suitable for cartilage repair was randomised to undergo either ACI or mosaicplasty; 58 patients had ACI and 42 mosaicplasty. Most lesions were post-traumatic and the mean size of the defect was 4.66 cm2. The mean duration of symptoms was 7.2 years and the mean number of previous operations, excluding arthroscopy, was 1.5. The mean follow-up was 19 months (12 to 26). Functional assessment using the modified Cincinatti and Stanmore scores and objective clinical assessment showed that 88% had excellent or good results after ACI compared with 69% after mosaicplasty. Arthroscopy at one year demonstrated excellent or good repairs in 82% after ACI and in 34% after mosaicplasty. All five patellar mosaicplasties failed. Our prospective, randomised, clinical trial has shown significant superiority of ACI over mosaicplasty for the repair of articular defects in the knee. The results for ACI are comparable with those in other studies, but those for mosaicplasty suggest that its continued use is of dubious value.
We reviewed the outcome of 146 Insall-Burstein II total knee replacements carried out in 121 patients over a period of nearly four years in a general orthopaedic unit. At a mean follow-up of ten years, 94 knees in 78 patients were available for review. Six patients (7 knees) were lost to follow-up and 37 (45 knees) had died. The clinical outcome using the scoring system of the Hospital for Special Surgery (HSS) was excellent or good in 79% of patients, fair in 14% and poor in 7%. The mean preoperative HSS score was 31, improving to 79 at the latest review. Using the newer rating system of the Knee Society, the mean score at ten years was 87 and the mean functional score 56. The arc of flexion improved from a mean preoperative value of 88° to 100°. The 18 patients who had had a previous high tibial osteotomy were analysed separately and were found to have benefited equally from the operation. Nine prostheses were revised, giving a cumulative survival rate of 92.3% at ten years. Radiological evaluation of 104 radiographs showed radiolucent lines around ten tibial components, none of which required revision. Anterior knee pain was a significant problem.
Between 1989 and 1993 we implanted a matrix support prosthesis made of carbon fibre for the treatment of chronic painful articular defects of the patella in 27 patients. The mean period of follow-up was 33 months (11 to 54) with clinical and arthroscopic evaluation of the implant. Overall, there were four excellent, three good, seven fair and 13 poor results. Nine patients subsequently had a patellectomy for persistent pain at a mean of 27 months after surgery (14 to 47). The mean visual analogue pain scores in those who retained their patella were 7.6 before operation and 5.5 at the time of the latest follow-up. Patient satisfaction for the entire group was 41%. There appeared to be good incorporation of the prosthesis and a satisfactory ingrowth of fibrocartilage, but the poor results in 48% and low patient satisfaction discourage us from recommending the procedure for lesions of the articular cartilage of the patella. The consistent seeding of the joint with carbon-fibre debris and a histiocytic giant-cell reaction in the synovium are also a cause for concern.