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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 mm. 2. (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


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 8 | Pages 1099 - 1109
1 Aug 2007
Munirah S Samsudin OC Chen HC Salmah SHS Aminuddin BS Ruszymah BHI

Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous ‘chondrocyte-fibrin’ construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis. All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O’Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage. Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI


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 mm. 2 . (100 to 1050) and the mosaicplasty group being 399.6 mm. 2. (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)


Bone & Joint 360
Vol. 1, Issue 3 | Pages 12 - 14
1 Jun 2012

The June 2012 Knee Roundup. 360. looks at: ACI and mosaicplasty; ACI after microfracture; exercise therapy and the degenerate medial meniscal tear; intra-articular bupivacaine or ropivacaine at knee arthroscopy; lateral trochlear inclination and patellofemoral osteoarthritis; bone loss and ACL reconstruction; assessing stability using the contralateral knee; tranexamic acid and a useful review of knee replacement


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/m. 2. ) than in overweight (n = 63; 25 to 30 kg/m. 2. ) and obese patients (n = 22; > 30 kg/m. 2. ). 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.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 2 | Pages 179 - 183
1 Feb 2005
Whittaker J Smith G Makwana N Roberts S Harrison PE Laing P Richardson JB

Autologous chondrocyte implantation (ACI) has been used most commonly as a treatment for cartilage defects in the knee and there are few studies of its use in other joints. We describe ten patients with an osteochondral lesion of the talus who underwent ACI using cartilage taken from the knee and were prospectively reviewed with a mean follow-up of 23 months. In nine patients the satisfaction score was ‘pleased’ or ‘extremely pleased’, which was sustained at four years. The mean Mazur ankle score increased by 23 points at a mean follow-up of 23 months. The Lysholm knee score returned to the pre-operative level at one year in three patients, with the remaining seven showing a reduction of 15% at 12 months, suggesting donor-site morbidity. Nine patients underwent arthroscopic examination at one year and all were shown to have filled defects and stable cartilage. Biopsies taken from graft sites showed mostly fibrocartilage with some hyaline cartilage. The short-term results of ACI for osteochondral lesions of the talus are good despite some morbidity at the donor site


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 1 | Pages 128 - 134
1 Jan 2005
Goldberg AJ Lee DA Bader DL Bentley G

An increasing number of patients are treated by autologous chondrocyte implantation (ACI). This study tests the hypothesis that culture within a defined chondrogenic medium containing TGF-β enhances the reexpression of a chondrocytic phenotype and the subsequent production of cartilaginous extracellular matrix by human chondrocytes used in ACI. Chondrocytes surplus to clinical requirements for ACI from 24 patients were pelleted and cultured in either DMEM (Dulbecco’s modified eagles medium)/ITS+Premix/TGF-β1 or DMEM/10%FCS (fetal calf serum) and were subsequently analysed biochemically and morphologically. Pellets cultured in DMEM/ITS+/TGF-β1 stained positively for type-II collagen, while those maintained in DMEM/10%FCS expressed type-I collagen. The pellets cultured in DMEM/ITS+/TGF-β1 were larger and contained significantly greater amounts of DNA and glycosaminoglycans. This study suggests that the use of a defined medium containing TGF-β is necessary to induce the re-expression of a differentiated chondrocytic phenotype and the subsequent stimulation of glycosaminoglycan and type-II collagen production by human monolayer expanded chondrocytes


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 2 | Pages 223 - 230
1 Mar 2003
Bentley G Biant LC Carrington RWJ Akmal M Goldberg A Williams AM Skinner JA Pringle J

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 cm. 2. 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


Bone & Joint 360
Vol. 4, Issue 4 | Pages 33 - 35
1 Aug 2015

The August 2015 Research Roundup360 looks at: Lightbulbs, bleeding and procedure durations; Infection and rheumatoid agents; Infection rates and ‘bundles of care’ revisited; ACI: new application for a proven technology?; Hydrogel coating given the thumbs up; Hydroxyapatite as a smart coating?


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 730 - 735
1 May 2005
Sharpe JR Ahmed SU Fleetcroft JP Martin R

In this study a combination of autologous chondrocyte implantation (ACI) and the osteochondral autograft transfer system (OATS) was used and evaluated as a treatment option for the repair of large areas of degenerative articular cartilage. We present the results at three years post-operatively. Osteochondral cores were used to restore the contour of articular cartilage in 13 patients with large lesions of the lateral femoral condyle (n = 5), medial femoral condyle (n = 7) and patella (n = 1). Autologous cultured chondrocytes were injected underneath a periosteal patch covering the cores. After one year, the patients had a significant improvement in their symptoms and after three years this level of improvement was maintained in ten of the 13 patients. Arthroscopic examination revealed that the osteochondral cores became well integrated with the surrounding cartilage. We conclude that the hybrid ACI/OATS technique provides a promising surgical approach for the treatment of patients with large degenerative osteochondral defects


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 4 | Pages 602 - 608
1 Apr 2010
Drobnič M Radosavljevič D Cör A Brittberg M Stražar K

We compared the quality of debridement of chondral lesions performed by four arthroscopic (SH, shaver; CU, curette; SHCU, shaver and curette; BP, bipolar electrodes) and one open technique (OPEN, scalpel and curette) which are used prior to autologous chondrocyte implantation (ACI). The ex vivo simulation of all five techniques was carried out on six juvenile equine stifle joints. The OPEN, SH and SHCU techniques were tested on knees harvested from six adult human cadavers. The most vertical walls with the least adjacent damage to cartilage were obtained with the OPEN technique. The CU and SHCU methods gave inferior, but still acceptable results whereas the SH technique alone resulted in a crater-like defect and the BP method undermined the cartilage wall. The subchondral bone was severely violated in all the equine samples which might have been peculiar to this model. The predominant depth of the debridement in the adult human samples was at the level of the calcified cartilage. Some minor penetrations of the subchondral end-plate were induced regardless of the instrumentation used. Our study suggests that not all routine arthroscopic instruments are suitable for the preparation of a defect for ACI. We have shown that the preferred debridement technique is either open or arthroscopically-assisted manual curettage. The use of juvenile equine stifles was not appropriate for the study of the cartilage-subchondral bone interface


Bone & Joint 360
Vol. 1, Issue 4 | Pages 12 - 15
1 Aug 2012

The August 2012 Knee Roundup. 360. looks at: meniscal defects and a polyurethane scaffold; which is best between a single or double bundle; OA of the knee; how to resolve anterior knee pain; whether yoga can be bad for your menisci; metal ions in the serum; whether ACI is any good; the ACL; whether hyaluronic acid delays collagen degradation; and hyaluronan and patellar tendinopathy


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 1 | Pages 61 - 64
1 Jan 2006
Krishnan SP Skinner JA Bartlett W Carrington RWJ Flanagan AM Briggs TWR Bentley G

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


The Bone & Joint Journal
Vol. 105-B, Issue 8 | Pages 880 - 887
1 Aug 2023
Onodera T Momma D Matsuoka M Kondo E Suzuki K Inoue M Higano M Iwasaki N

Aims

Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury.

Methods

A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm2) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 723 - 738
4 Oct 2022
Liu Z Shen P Lu C Chou S Tien Y

Aims

Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism.

Methods

Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67phox was involved in suramin-enhanced chondrocyte phenotype maintenance.


Bone & Joint Research
Vol. 12, Issue 7 | Pages 397 - 411
3 Jul 2023
Ruan X Gu J Chen M Zhao F Aili M Zhang D

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.


The Bone & Joint Journal
Vol. 106-B, Issue 8 | Pages 775 - 782
1 Aug 2024
Wagner M Schaller L Endstrasser F Vavron P Braito M Schmaranzer E Schmaranzer F Brunner A

Aims

Hip arthroscopy has gained prominence as a primary surgical intervention for symptomatic femoroacetabular impingement (FAI). This study aimed to identify radiological features, and their combinations, that predict the outcome of hip arthroscopy for FAI.

Methods

A prognostic cross-sectional cohort study was conducted involving patients from a single centre who underwent hip arthroscopy between January 2013 and April 2021. Radiological metrics measured on conventional radiographs and magnetic resonance arthrography were systematically assessed. The study analyzed the relationship between these metrics and complication rates, revision rates, and patient-reported outcomes.


The Bone & Joint Journal
Vol. 106-B, Issue 5 Supple B | Pages 32 - 39
1 May 2024
Briem T Stephan A Stadelmann VA Fischer MA Pfirrmann CWA Rüdiger HA Leunig M

Aims

The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI).

Methods

This single-centre study focused on a cohort of 24 patients with cam- or pincer-type FAI, full-thickness femoral or acetabular chondral lesions, or osteochondral lesions ≥ 2 cm2, who underwent surgical hip dislocation for FAI correction in combination with AMIC between March 2009 and February 2016. Baseline data were retrospectively obtained from patient files. Mid-term outcomes were prospectively collected at a follow-up in 2020: cartilage repair tissue quality was evaluated by MRI using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Patient-reported outcome measures (PROMs) included the Oxford Hip Score (OHS) and Core Outcome Measure Index (COMI). Clinical examination included range of motion, impingement tests, and pain.


Bone & Joint Research
Vol. 11, Issue 6 | Pages 349 - 361
9 Jun 2022
Jun Z Yuping W Yanran H Ziming L Yuwan L Xizhong Z Zhilin W Xiaoji L

Aims

The purpose of this study was to explore a simple and effective method of preparing human acellular amniotic membrane (HAAM) scaffolds, and explore the effect of HAAM scaffolds with juvenile cartilage fragments (JCFs) on osteochondral defects.

Methods

HAAM scaffolds were constructed via trypsinization from fresh human amniotic membrane (HAM). The characteristics of the HAAM scaffolds were evaluated by haematoxylin and eosin (H&E) staining, picrosirius red staining, type II collagen immunostaining, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Human amniotic mesenchymal stem cells (hAMSCs) were isolated, and stemness was verified by multilineage differentiation. Then, third-generation (P3) hAMSCs were seeded on the HAAM scaffolds, and phalloidin staining and SEM were used to detect the growth of hAMSCs on the HAAM scaffolds. Osteochondral defects (diameter: 3.5 mm; depth: 3 mm) were created in the right patellar grooves of 20 New Zealand White rabbits. The rabbits were randomly divided into four groups: the control group (n = 5), the HAAM scaffolds group (n = 5), the JCFs group (n = 5), and the HAAM + JCFs group (n = 5). Macroscopic and histological assessments of the regenerated tissue were evaluated to validate the treatment results at 12 weeks.