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Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLI | Pages 98 - 98
1 Sep 2012
Hardisty G Dixon S Janes G Harvey L Baddour E
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The technique of Matrix Induced Autologous Chondrocyte Transplantation (MACI) is well established with satisfactory outcomes up to five years in the knee. Fewer series describe the outcomes of this technique in the ankle. We present the functional outcomes of the technique for a single surgeon series in a general hospital setting. Twenty-seven patients, mean age 41, were reviewed at 3.7 (range, 1 to 5) years. Patients were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) hind-foot scale, Tegener activity score and University of California lower extremity activity scale. MRI findings were also reviewed. While most patients report a significant improvement in symptoms with full return to activities of daily living, 36% of those under 40 and 78% of those over 40 reported restricted recreational activity. Of the patients under 40 years of age, 86% were able to run compared with 23% of those over 40. Of patients over 40, 64% continued to have moderate or severe pain. Careful preoperative counselling is required for patients of all ages regarding likely outcomes. In patients over 40 the procedure is unlikely to give good pain relief and alternative options should be considered


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_13 | Pages 21 - 21
1 Mar 2013
RAHMAN J KAYANI B GILLOTT E BENTLEY G SKINNER J MILES J CARRINGTON R BRIGGS T
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The Royal National Orthopaedic Hospital has completed an extensive trial of ACI versus MACI in the treatment of symptomatic osteochondral defects of the knee. A new technique has now been proposed which is quicker and easier to perform. This is the Gel-Type Autologous Chondrocyte Transplantation, CHONDRONTM. At Stanmore CHONDRON has been used for the past 17 months. Our aim was to assess the short term functional outcome of patients who have undergone CHONDRONTM using validated outcome scoring questionnaires. We retrospectively reviewed the notes of 43 patients that had undergone CHONDRONTM over one year ago and scored them using the Modified Cincinnati Score, the Visual Analogue Score and the Benltey Stanmore Functional Rating Score. RESULTS. The mean pre-operative Modified Cincinnati Score was 39.9, which improved to a mean of 59.8 post-operatively. The mean Visual Analogue Score improved from 6.7 to 5.1 post-operatively. The median Bentley Functional Rating Score was 3 pre-operatively and 2 post-operatively. CONCLUSIONS. These early results show that 76% of the patients who were treated with CHONDRONTM experienced a reduction in pain and improvement in post-operative function. In the patients in whom the symptoms were worse, the deterioration in score could be partly explained by numerous previous procedures on the same site, presence of early osteoarthritis or the presence of multiple osteochondral lesions. This highlights the importance of careful patient selection in order to gain maximum benefit from the procedure


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 59 - 60
1 Mar 2005
Marcacci M Kon E Zaffagnini S Marchesini L Iacono F Neri M Spinel M
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Autologous chondrocyte transplantation has become a possible solution for the treatment of chondral knee lesions. In the last years matrix autologous chondrocyte transplantation procedures were developed by various scientists. We selected a biodegradable, hyaluronian-based biocompatible scaffold for cell proliferation. This nonwoven three-dimensional structure consists of a network of 20 – B5-thick fibers with interstices of variable sizes which constitute an optimal physical support to allow cell-cell contacts, cluster formation, and extracellular matrix deposition in order to create a bioengenerized cartilage Hyalograft C. The easy handling of Hyalograft C in open surgery has suggested us to investigate its possible use by an arthroscopic procedure.

Arthroscopic technique has been used from December 2000 in 88 cases. At December 2003 45 patients achieved at least 1 year follow up and 22 patients – 2 years follow up.

All the patients were clinically evaluated was analyzed according to the International Repair Cartilage Society score at 12 and 24 months. Returning back to sport was also recorded. We were able to obtain CT scans or MRI images for all patients at 6, 12 and 24 months of follow up.

No complications related to the implant and no serious adverse events were observed during the treatment and follow up period. The IKDC objective score improved after 12 months in all patients, showing a normal or nearly normal knee in 96,7% of patients. The mean IKDC subjective score obtained was 41,3 at baseline, 76.9 at the 12 months follow-up control, and 75,9 after 24 months. The worsening of IKDC score was noted in 1 of 22 patients analyzed at 12 and 24 months follow up.

A second look arthroscopy was performed in 11 patients at 12 months follow up and a complete healing of the defect and the excellent quality of regenerated cartilage was noted at macroscopic examination. The histological evaluation in 6 cases has demonstrated the hyaline type of new cartilage, although not completely mature.

This matrix autologous chondrocyte transplantation procedure avoids the use of periosteal flap, simplify the surgical procedure and permit to perform the arthroscopic implant. Thus, complications as hypertrophy or ossification of periosteal flap are avoided and the surgical morbidity and the recovery time for the patient are extremely reduced. The preliminary clinical and histological results are encouraging but the decree absolute on the efficiency of this method will be assessed at longer follow up.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 6 - 6
1 Mar 2008
David L Mahroof S Pringle J Bayliss M Briggs T
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This prospective study analyses the histological results of autologous chondrocyte transplantation in patients with articular cartilage defects of the knee joint. Chondrocytes from a non-weight bearing area of the knee were harvested and then cultured in vitro.

Re-implantation involved injection of the chondrocytes into the defect, which was then sealed with a collagen membrane. One year post-op, patients were evaluated by clinical, arthroscopic and histological assessment. A biopsy of the transplanted region was examined by staining with Erlich’s H& E and Safranin 0, polarised light microscopy and by analysis with S100 and immunohistochemistry. Hyaline cartilage content was further assessed by examination of Type IIa & lIb collagen mRNA expression using in-situ hybridisation.

The median age was 31 years. 63 knees were treated. Solitary lesions were treated in 61 knees with two defects being treated in three knees (66 defects in total). The defects were located on the medial femoral condyle in 39 cases, lateral femoral condyle in 14, trochlea in 2 and patella in 11. The defect size ranged from 1–7 cm2 (mean area 3cm2 ). 40 patients had at least one-year follow-up. Using the Brittberg Rating, 11 had excellent results, with 15 good, 10 fair and 4 poor. The mean Lysholm and Gillquist scores improved from 44 pre-op to 77 one-year post-op. Biopsy at one year conftrmed the presence of hyaline cartilage in 22 out of 32 cases (69%). In-situ hybridisation confirmed the presence of Collagen type II in the deep zones of the biopsy with a fibrocartilaginous appearance superficially.

Conclusion: This technique can provide an effective treatment for cartilage defects. The histological results are encouraging and chondrocyte transplantation may be the only procedure to allow regeneration of hyaline like articular cartilage.


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

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


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 286 - 287
1 Nov 2002
Zheng M
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Introduction: Autologous chondrocyte transplantation (ACT) has been shown to be a promising method for restoring hyaline cartilage defects. Since it was first reported by Brittberg et al nine years worth of clinical follow up studies indicate that ACT has provided an excellent outcome in the restoration of hyaline cartilage. As ACT relies on the use of cultured cells and the biosynthetic profile of cultured chondrocytes has been shown to be altered during in vitro expansion, cultivation of chondrocytes for ACT has presented many technical and quality control challenges.

Aim: To perform an assessment of the cellular phenotype of cultured chondrocytes, consistent with differentiation of articular hyaline cartilage, to ensure the delivery of ACT for restoration of hyaline cartilage.

Methods: Using RT-PCR and flow cytometry analyses, we characterised the cellular phenotype of culture chondrocytes used for ACT. We examined several transcriptional factors, cytokines and matrix proteins necessary for the differentiation of chondrocytes in a total of 15 cases of ACT. These included SOX9, Cbfa1, Indian Hedgehog (Ihh), TGF-b3, BMP-2, PTHrP, type I and type II collagen, aggrecan and alkaline phosphatase.

Results: The results demonstrated that there is a variety in the expression of these genetic makers but cultured cells used for ACT were within the programme of chondrocyte differentiation. Furthermore, there is variation in the level of apoptosis of chondrocytes between patients as evidenced by annexin V flow cytometry. As evidenced by MRI in two patient samples, apoptosis of chondrocytes greater than 8% was coincident with cases that could not restore hyaline cartilage three months after ACT.

Conclusions: Given that there is a medical need for ACT in the treatment of articular cartilage injury, a process for monitoring the quality of culture chondrocyte prior to implantation may provide a better clinical outcome of ACT.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 161 - 162
1 Jul 2002
David LA Pringle J Briggs TWR
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Introduction: Articular cartilage defects in the knee joint have poor capacity for repair. The purpose of this study is to analyse the short-term results of the treatment of deep chondral defects with autologous chondrocyte transplantation with the use of a collagen membrane.

Methods: This is a prospective study involving twentytwo consecutive patients receiving autologous chondrocyte transplantation. Chondrocytes from a non weight bearing area of the knee are harvested, then isolated and cultured in vitro. Re-implantation involves injection of the chondrocytes into the defect which is then sealed with a porcine I/III (Chondro-gide) membrane. Evaluation consists of clinical assessment, arthroscopy and histological examination.

Results: The patients were treated between July 1998 and December 2000. The age range of the patients was 15–51 years (mean age 31 years). Of the 22 patients treated, 13 had right-sided lesions, 11 had left-sided lesions with two patients receiving bilateral procedures. Solitary lesions were treated in 23 knees with two defects being treated in one knee (25 defects in total). The defects were located on the medial femoral condyle in 17 cases, the lateral femoral condyle in five, the trochlea in two and the patella in one case. The defect size ranged from 1–5.4cm2 (mean area 2.65cm2). The follow-up of the patients ranges from 1–28 months (mean 14 months). Thirteen patients have at least one-year follow-up. Of these patients, using the Brittberg Rating, two patients have excellent results at one year, with six good, four fair and one poor. The mean Lysholm and GilIquist scores improved from 50 pre-op to 72 one-year post-op and the mean Verbal Numerical Pain Scores improved from 7.2 to 2.6. Arthroscopy revealed that the transplants were level with the surrounding surface in most cases. Biopsy at one year confirmed the presence of hyaline cartilage in 10 out of 13 cases.

Conclusion: Although the results are short-term, autologous chondrocyte transplantation using the Chondro-gide membrane can provide, with careful patient selection, an effective treatment for cartilage defects of the knee. Chondrocyte transplantation may be the only procedure to allow regeneration of hyaline articular cartilage.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 113 - 113
1 Mar 2006
Bitter T Gille J Russlies M Kurz B Behrens P
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Introduction: We developed a new treatment option for localized articular cartilage defects: the matrix-induced, autologous chondrocyte transplantation (MACT) in which we seeded autologous chondrocytes on porcine porous matrices of type I/III collagen (Chondro-Gide®, Geistlich Biomaterials, Wolhusen, Switzerland) instead of a periosteum flap.The target of this clinical prospective study was to evaluate the outcome for a follow up period of five years after transplantation.

Methods: Between 1998 and 2001 we treated 38 patients (19 male and 19 female) with localized cartilage defects (Outerbridge grade three to four). Within the follow up time of this study until October 2002 the patients were assessed clinically 3, 6, 12, 18, 24, 36 and 60 month after the transplantation using four different standard rating scales: the Meyers-score, the Tegner/Lysholm-score, the Lysholm/Gilquist-score and the ICRS-score as well as MRI. Results were documented and compared with the pre operatives. Furthermore histological stainings of four patients were assessed.

Results: Mean patient age was 35 years (19 to 58 years). Average defect size was 5,6 qcm, 10 defects localized patellar, 16 femoral medial,3 femoral lateral and 9 combined. Two years after operation 66,7% (n=25) of the patients rated the function of their knee as much better or better than before in the subjective evaluation. After five years the percentage decreased to 57,1% (n=10). Up to a follow-up time of 24 month the clinical outcome of all four scores illustrated an significant improvement. Five years after transplantation two scores still showed significant improvement (Meyers-score: p= 0,02; Lysholm-Gilquist-Score: p=0,02). The other two scores showed improvement which turned out to be non significant (Tegner-Lysholm-Score: p=0,19; ICRS-Score: p=0,06) MRI scanning results after one year could not detect the quality of cartilage defect repair. Histological evaluation of four patients might not identify any association between the quality of the tissue and the clinical outcome

Conclusion: Five years results in two scores (Meyer- and Lysholm-Gilquist-Score) still showing significant improvement imply that MACT has turned out to be an acceptable alternative for the treatment of localized cartilage defects in the knee.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_II | Pages 198 - 198
1 Apr 2005
Rosa D Leopardi P di Vico G Iacono V Di Costanzo M
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Autologous chondrocyte implant (ACI) is a very effective technique in the treatment of chondral lesions in order to restore normal hyaline cartilage. This technique, reported for the first time by Peterson in 1994, is advised for young or middle-aged. active patients with a single painful chondral injury (3/4 grade of Outerbridge scale), starting from more than 2 cm². New tissue engineering techniques with the use of biomaterial derived from hyaluronic acid (HYAFF matrix) provide ideal support for the culture and proliferation of chondrocytes, allowing at the same time arthroscopic implant. There are many advantages of arthroscopic techniques: easy implant and less pain post-operatively; however, the indications for arthroscopic technique are still restricted: single chondral inury, 2–6 cm² in size and localisation at the femoral condyles.

At the Department of Orthopaedic Surgery of the University “ Federico II ” of Naples starting from January 1996 to the present, 29 patients were treated with ACI. Eight patients (six men and two women) had an arthroscopic implant. Median age was 18; in seven patients an OCD of the medial femoral condyle was present and just one patient had a post-traumatic injury of the medial femoral condyle. Hyalograft was used in all cases. All patients underwent CPM starting from the second post-operative day and full charge was allowed after 2 months. All patients were evaluated by clinical examination with IKDC score and functional score (Tegner) at 3, 6 and 12 months after surgery and with a MNR at 6 and 12 months after surgery and then every year.

Good results were found subjectively in 88% of the patients, with a complete lack of pain in 70% cases. Using the IKDC score good results were found in 85% of the cases (average score 90). With the Tegner score we reported an improvement in the level of activity in 60% of the cases.

The MNR images, performed with standard sequences, fat-suppressed and in the last cases with dGEMRIC, showed the presence of regeneration tissue inside the chondral defects, with a signal very similar to that of the cartilage tissue, sometimes slightly deeper.

Our experience shows that ACI is an effective way of treating chondral lesions with excellent results. We think that progress in the field of biomaterials will extend the indications for arthroscopic techniques, also allowing implants in larger lesions and at other sites.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 59 - 59
1 Mar 2005
Giannini S Buda R Grigolo B Vannini F
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The purpose of this study is to demonstrate the validity of the autologous chondrocytes transplantation (A.C.T.) technique implemented over the last 6 years in the treatment of osteochondral lesions of the talus.

Our case study included 22 patients (12 males and 10 females), with an average age of 27 years affected by osteochondral lesions of the talus surface. All lesions were > 1.5 cm2, monofocal, and post-traumatic in origin. The first 9 patients received ACT (Genzyme technique) and the remaining 13 patients received ACT with an arthroscopic technique. In 6 of the patients, the cartilage harvested from the detached osteochondral fragment was used for culturing, avoiding the first step arthroscopy in the knee. Before surgery, all patients were assessed clinically, radiographically, and using MRIs. For clinical evaluation patients were assessed using the American Foot & Ankle Society 100 point score. Before surgery the mean score was 48.4 points. 11 patients underwent second-look arthroscopy at one year during which a biopsy was harvested for histologic analysis of the reconstructed cartilage. Of these, 9 patients (Genzyme technique) also had hardware removed.

The mean follow-up of the 22 patients was 36 months. At follow-up, all patients but one were satisfied with their results. With regards to the clinical results evaluated using the American Foot and Ankle Society score, an average of 90.5 was obtained at 24 months, while at 36 months the average score (19 patients) was 94.0 (range 54–100). During follow-up arthroscopy, 4 patients had mild fibrosis and 1 patient required regularization of flap overgrowth causing pain.

The clinical and histological results have confirmed the validity of the surgical technique utilized with no subjective nor objective complications. An improvement of the symptoms and of articular function has also been observed: laboratory data confirmed the histological appearance of the newly formed hyaline cartilage in all cases evaluated. Immunohistochemistry showed a positive staining for collagen type II located in the extracellular matrix and in the chondrocytes in the healthy and transplanted cartilage biopsies. All the specimens studied were also positive for proteoglycans expression as was the Alcian blue reaction, which highlighted the presence of these fundamental components of a cartilaginous matrix.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 213 - 213
1 Mar 2004
Peterson L
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Autologous chondrocyte transplantation is a two-stage procedure for treating full-thickness chondral and osteochondral joint lesions. It has been used in more than 1200 patients in Sweden and 8000 outside of Sweden.

No serious general complications have been seen, no deep infections, no deep thrombosis.

Relevant serious complications are graft delaminations, especially in partial or total loss of attatchment. These can be a result of inadequate surgical technique, too aggressive rehabilitation or too early return to competitive highimpact sports. They often occur 6–12 months postop. Marginal delaminations can be handled by debridement and microfracture. Partial and total graft delaminations need retransplantation. This can be performed with good result. More common complications are periosteal delamination and hypertrophy of the periosteal flap causing catching, pain and swelling. If symptoms does not disappear with a change in rehabilitation an arthroscopic debridement is necessary.

Arthrofibrosis with limited R.O.M. is treated with intensified physical therapy. If that fails arthroscopic debridement is needed. Other relevant complications like infection and thrombosis could usually be prevented.


The Journal of Bone & Joint Surgery British Volume
Vol. 79-B, Issue 5 | Pages 831 - 836
1 Sep 1997
Frenkel SR Toolan B Menche D Pitman MI Pachence JM

We have developed a novel, two-layered, collagen matrix seeded with chondrocytes for repair of articular cartilage. It consists of a dense collagen layer which is in contact with bone and a porous matrix to support the seeded chondrocytes. The matrices were implanted in rabbit femoral trochleas for up to 24 weeks. The control groups received either a matrix without cells or no implant.

The best histological repair was seen with cell-seeded implants. The permeability and glycosaminoglycan content of both implant groups were nearly normal, but were significantly less in tissue from empty defects. The type-II collagen content of the seeded implants was normal. For unseeded implants it was 74.3% of the normal and for empty defects only 20%. The current treatments for articular injury often result in a fibrous repair which deteriorates with time. This bilayer implant allowed sustained hyaline-like repair of articular defects during the entire six-month period of observation.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 115 - 115
1 Mar 2006
Andrea F
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Since June 2002 15 hip autologous chondrocyte transplantations were arthroscopically performed for both acetabular roof and femoral head chondral defects.

15 Patients affected by chondral defect in the hip joint were treated with autologous chondrocyte transplantation. The mean follow up was 13.8 months (range 16 – 12 months) and the chondral defect was classified as 3rd – 4th degree, according to the Outerbridge’s classification. The defects were located on the acetabular roof in 12 cases, on the femoral head in 2 cases and on booths articular surfaces in 1 case.

9 patients were female and 6 male. The mean age was 40.7 years (from 52 to 22).In all cases the procedure was arthroscopically performed.

A Bioseed C tissue was employed as a scaffold for chondrocytes, cultured in a tridimentional shape.

A group of untreated 15 patients, matched for chondral defect degree, sex distribution and mean age was selected as control.

All the Patients of both groups were pre and post operatively evaluated with the Harris Hip Score (HHS).

Patients treated with hip autologous chondrocyte transplantation significantly improved after surgery (mean pre-op HHS 51.3; mean post-op HHS 85.3) compared with the untreated group (mean pre-op HHS 52.1; mean post-op HHS 64.5). Worst results were obtained in Patients affected by chondral defect located on the femoral head and when the joint space was reduced.

Hip arthroscopy steel represent a new approach for treatment of hip’s disorders. Chondral defects of the hip can be treated with autologous chondrocyte transplantation, performed by hip arthroscopy. This study demonstrates the efficacy of this procedure compared with untreated patients.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 426 - 427
1 Oct 2006
Marcacci M Kon E Zaffagnini S Reggiani LM Filardo G Delcogliano M Iacono F Neri M
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Introduction: In the last years matrix autologous chondrocyte transplantation becomes a possible solution in the treatment of chondral lesions. We develop an arthroscopic procedure for chondrocyte implant on hyaluronian-based scaffold.

Material and methods: Thirty-five patients treated using this technique achieved 3 years follow up. All the patients were clinically evaluated using IKDC score and with MRI or TC scan. In some Patients we performed a second look arthroscopy and histological evaluation.

Results: IKDC objective score improved after 12 months in all patients and the results were confirmed at 24 and 36 months of follow-up. The improving was obtained also according to IKDC subjective score. A second look arthroscopy showed healing of the defect with regenerated cartilage. The histological evaluation has demonstrated in 80% the hyaline type of new cartilage.

Conclusions: This matrix autologous chondrocyte transplantation procedure avoids the use of periosteal flap, simplify the surgical procedure and permit to perform the arthroscopic implant reducing the morbidity of the procedure. The preliminary clinical and histological results at 3 years follow-up are encouraging.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 113 - 114
1 Mar 2006
David L Mahroof S Pringle J Bayliss M Briggs T
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Aim: This prospective study analyses the histological results of autologous chondrocyte transplantation in patients with articular cartilage defects of the knee joint.

Methods: This is a prospective, single centre, single surgeon study. Consecutive patients undergoing autologous chondrocyte transplantation were studied. Chondrocytes from a non-weight bearing area of the knee were harvested and then cultured in vitro. Re-implantation involved injection of the chondrocytes into the defect, which was then sealed with a collagen membrane. One year post-op, patients were evaluated by clinical, arthroscopic and histological assessment. A biopsy of the transplanted region was examined by staining with Erlich’s H& E and Safranin O, polarised light microscopy and by analysis with S100 and immunohistochemistry. Hyaline cartilage content was further assessed by examination of Type IIa & IIb collagen mRNA expression using in-situ hybridisation.

Results: The median age was 31 years. 63 knees were treated. Solitary lesions were treated in 61 knees with two defects being treated in three knees (66 defects in total). The defects were located on the medial femoral condyle in 39 cases, lateral femoral condyle in 14, trochlea in 2 and patella in 11. The defect size ranged from 1–7 cm2 (mean area 3cm2). 40 patients had at least two-year follow-up. Using the Brittberg Rating, 11 had excellent results, with 15 good, 10 fair and 4 poor. The mean Lysholm and Gillquist scores improved from 44 pre-op to 77 two-years post-op. Biopsy at one year confirmed the presence of hyaline cartilage in 22 out of 32 cases (69%). In-situ hybridisation confirmed the presence of Collagen type II in the deep zones of the biopsy with a fibrocartilaginous appearance superficially.

Conclusion This technique can provide an effective treatment for cartilage defects. The histological results are encouraging. Chondrocyte transplantation appears to regenerate tissue with the features of normal hyaline cartilage.


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

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

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

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

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


Orthopaedic Proceedings
Vol. 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. 87-B, Issue SUPP_III | Pages 234 - 235
1 Sep 2005
Libera J Moos V Meisel HJ Hutton W Josimovic-Alasevic O
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Study Design: Experimental study in dogs:

Objective: To assess the efficiency of disc chondrocyte transplantation in a canine model.

Summary of Background Data: Conventional clinical treatments of intervertebral disc herniation and degeneration are focused on excision of damaged tissue, stabilization, and spinal fusion. The development and refinement of cell-based therapeutics for tissue regeneration and repair have spawned a multitude of applications including autologous disc chondrocyte transplantation. For clinical application the efficiency of disc chondrocyte transplantation was assessed using a pre-clinical canine model to show the technical feasibility and biological relevance for disc repair and retardation of disc degeneration. This report examined the protein expression of transplanted disc chondrocytes and their role in the clinically observed disc repair following autologous disc chondrocyte transplantation.

Methods: The nucleus and inner annulus were sampled from four skeletally-mature dogs by micro-discectomy. Disc chondrocytes were isolated and propagated under GMP validated conditions including completely autologous serum conditions. Two months later, the cultured cells were transplanted through the contralateral side of experimental discs after testing complete healing of the annulus by measuring intradiscal pressure stability. After seven months the animals were humanely killed. One half of the vertically halved lumbar spines were embedded in paraffin and sections were analysed histologically and immunohistochemically.

Results: Histological examinations revealed large clusters of cells within the nucleus area of the treated discs. Cells within these cell clones were found to be viable and surrounded by de novo synthesized matrix as evidenced by a distinct histological staining and immunohistochemical expression pattern. A disc-specific expression of collagen type I and II and hyaline-specific proteoglycans was observed indicating the regenerative and reconstructive capacity of the transplanted disc chondrocytes.

Conclusions: These results indicate the contribution of transplanted disc chondrocytes to the observed clinical success of this cell-based therapy.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 274 - 274
1 Sep 2005
de Beer J du Toit D Roberts C Huijsmans P Muller C Geldenhuys K Lyners R van Rooyen K de Jongh H
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The research question was: can ex-vivo chondrocyte cultures be established in shoulder cartilage biopsies?

Arthroscopic or open biopsies were obtained, with informed consent and institution-approved review protocol, from patients undergoing total shoulder replacement or orthopaedic interventions for end-stage rotator cuff deficiency or arthropathy. Chondrocytes were isolated from eight biopsies and cells cultured over 4-weeks.

In the first week post-digestion, validation studies showed cell counts varying from 30 000 to 400 000 (mean 126 666) and viability ranging from 30% to 100% (mean 75.2%). No primary culture failures were observed. One of the eight had an unexplained lower cell count and viability. Viability exceeded 80% in six of the eight cultures (75%). Alcian Blue stains and flow cytometry (Facscan) confirmed stable cultures with matrix formation. Aggrecan studies are in progress.

The fact that ex-vivo chondrocyte cultures can be established in biopsied shoulder cartilage may prove encouraging for autologous chondrocyte transplant in selected patients meeting stringent inclusion criteria.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 143 - 143
1 Mar 2009
Koulalis D Schultz W Mastrokalos D Zachos K Karaliotas G Menelaou M Liberis I
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Aim of study: Comparison of clinical and radiological results of the applied methods.

Material and method: 20 patients with osteochondritis dissecans of the talus were treated. Autologous chondrocyte transplantation was applied to a group of 10 patients (Group A) and autologous osteochondral transplantation to the rest 10 patients (Group B).Group A: Average-age=30,8 years, -follow up time= 33,6 (12–48) months, -lesion size= 20×16,2 (35–15 × 25–15) mm and depth =7 (20–5) mmGroup B: Average –age =33, 7 years, follow up time =32,4 (12–48) months, – lesion size=16,5×15 (25–10 × 20–10) mm and depth=4 (5–3) mm.All patients underwent clinical und radiological investigation and the symptoms were classified in accordance with the Finsen classification. Group A was treated with autologous chondrocyte and Group B with autologous osteochondral transplantation. Osteotomy of the medial or lateral malleolus was necessary by 6 Group A – patients and 4 Group B – patients. Postoperative treatment : Non-weight bearing for 6 weeks, continuous passive motion of the joint, clinical and radiological follow up 3rd, 6th, 12th and yearly basis

Results: Postoperatively the average Finsen score showed for Group A an improvement from 3,5 (very bad) to 1,1 (excellent) and for Group B from 3,6 (very bad) to 1 (excellent). MRI follow up showed defect coverage by 7 patients of Group A and 9 patients of Group B after 12 months. Second look arthroscopy was performed by 4 patient of Group A and 3 patients of Group B showing full coverage of the defect site. Complications: persisting swelling for an average time of 2,7 months in Group A and 4,3 months in Group B. Additionally 10 degrees loss of joint extension in 4 patients of Group A and 3 patients of Group B.

Conclusion: Autologous chondrocyte transplantation as well as autologous osteochondral transplantation present very good clinical results. As methods of articular surface restoration they have their advantages and disadvantages playing an important role in chosing one of them, in combination always with the surgeons philosophy. The existence of these methods is important in influencing the course of the ankle joint towards a good prognosis, in cases of osteochondral lesion. Further investigation is necessary.


Purpose of the study: Autologous chondrocyte transplantation has become in the last years more and more popular for the treatment of chondral knee lesion. The standard procedure has good result, however important disadvantages represent the difficulty to manage liquid chondrocyte culture solution and the necessity to create the hermatic periosteum suture.The aim of the our study was to investigate the short time results of a matrix-induced chondrocyte transplantation (MACT) for treatment cartilage defects in the knee und to analyse ad- or disadvantages.

Method: Since June 2001 we use for the autologous chondrocyte transplantation (ACT) instead of a periosteum flap the 3-dimensional matrix or resorbarble fleece. 35 patients with defects in cartilage of the knee have been treated so far. Average defect size was 4,8 qcm, all patients had a follow up with clinical investigations and MRI studies. The results were evaluated by different scores.

Results: 33 of 35 patients were after six months satisfied with the operation result or justed it more better. All of the subjective or objektive parameters of the different scores were improved after one year. The clinical outcome was good in the follow-up.

Conclusion: In the follow up the results can be compared with the one found in literature of the standard periost method. The matrix-induced chondrocyte transplantation has the advantage, that no periost flap is needed and that the chondrocyte culture is not liqiud. The first results are promising.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 1 | Pages 62 - 67
1 Jan 2012
Aurich M Hofmann GO Mückley T Mollenhauer J Rolauffs B

We attempted to characterise the biological quality and regenerative potential of chondrocytes in osteochondritis dissecans (OCD). Dissected fragments from ten patients with OCD of the knee (mean age 27.8 years (16 to 49)) were harvested at arthroscopy. A sample of cartilage from the intercondylar notch was taken from the same joint and from the notch of ten patients with a traumatic cartilage defect (mean age 31.6 years (19 to 52)). Chondrocytes were extracted and subsequently cultured. Collagen types 1, 2, and 10 mRNA were quantified by polymerase chain reaction. Compared with the notch chondrocytes, cells from the dissecate expressed similar levels of collagen types 1 and 2 mRNA. The level of collagen type 10 message was 50 times lower after cell culture, indicating a loss of hypertrophic cells or genes. The high viability, retained capacity to differentiate and metabolic activity of the extracted cells suggests preservation of the intrinsic repair capability of these dissecates. Molecular analysis indicated a phenotypic modulation of the expanded dissecate chondrocytes towards a normal phenotype. Our findings suggest that cartilage taken from the dissecate can be reasonably used as a cell source for chondrocyte implantation procedures.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 583 - 584
1 Aug 2008
Rathinam M McGee A Spalding TJW
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Aims: To assess the outcome of biological resurfacing combined with osteotomy for knee osteoarthritis [OA] in young individuals. Methods: Between January 2001 and March 2006, 25 active patients with unicompartmental OA were treated with a combination of cartilage resurfacing and tibial or femoral osteotomy. The cartilage resurfacing procedure was microfracture on both surfaces in 20 patients, Matrix Autologous Chondrocyte Implantation in 3, Autologous Chondrocyte Transplantation in 1 and Meniscal transplantation in 1. For limb realignment, an open wedge High Tibial Osteotomy was performed in 23 patients and Distal Femoral Osteotomy in 2 patients, using either the Puddu plate (Arthrex) or the Tomofix plate (Synthes). There were 23 male and 2 female patients with a mean age of 45 years (range 27 to 60). The median follow-up period was 22.5 months (range 6 to 60). At follow-up patients were assessed radiographically and clinically using the knee society clinical score [KSS] and the Tegner activity scale. Results: The outcome was satisfactory in 20 patients who had improvement in pain and function. The median Tegner activity level was 5.5 and the median KSS was 164. Poor results in five patients were due to delayed union in 1, nonunion in 2 and persistent severe pain in 2 who subsequently underwent unicompartmental or total knee replacement. Discussion and conclusion: Management of the young active individual with grade 4 bare bone arthritis in the knee is challenging, and arthroplasty may not provide the ideal solution. Our series has shown that combining opening wedge osteotomy with cartilage repair results in improvement in a high proportion of patients. Such salvage surgery or ‘biological resurfacing’ may therefore have a place in the management of active young patients with bare bone osteoarthritis


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 105 - 105
1 Mar 2006
Fritz J Albrecht D Schewe B Krackhardt T Gaissmaier C Weise K
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Introduction: Within the last few years numerous operative procedures have been described aiming a biological repair of damaged articular cartilage. Current techniques are: Microfracture, Osteochondral Autografting (Mosaicplasty) and Autologous Chondrocyte Transplantation (ACT). Several new studies have shown, that the defect size plays a major role in the clinical outcome of the different procedures. Thus, it makes sense to measure the size of a cartilage defect before indicating a certain method for biological repair. Material and Methods: We have developed a software (beta-version) for measuring the size of a cartilage defect during a routine arthroscopy in a real-time mode. The programme is based on an Infrared-Navigation tool (Orthopilot, B.Braun-Aesculap, Germany). In order to proof the reliability and the usefulness of this device, we carried out following study: in each of 6 cadaver-knees we performed 2 full-thickness cartilage defects (MFC and LFC) of different size. In a first run 3 surgeons had to scope the joint and estimate the defect size with means of a scaled probe-hook. In a second run we performed a measurement of the defect with the Orthopilot™; finally an open measurement after arthrotomy was done to act as reference. Results: Measurement of the cartilage defect size was clearly superior to an estimation by probehook. Especially the inter-observer difference between the surgeons was widely spread, whereas the max. mismeasurement with the Orthopilot was 2mm. Discussion: Our study has shown, that navigational-assisted determination of chondral defects is superior to a simple estimation of a defect size by a probehook. Considering that the defect size is a crucial point in choosing the appropriate procedure for the treatment of cartilage defects, navigation devices like the CDM-software is maybe a helpful tool in making the right decision for a suitable method of biological cartilage repair