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 p67. phox. was involved in suramin-enhanced chondrocyte phenotype maintenance. Results. Suramin enhanced the COL2A1 and ACAN expression and lowered COL1A1 synthesis. Also, in 3D pellet culture GAG and COL2A1 production was significantly higher in pellets consisting of chondrocytes expanded with suramin compared to controls. Surprisingly, suramin also increased ROS generation, which is largely caused by enhanced NOX (p67. phox. ) activity and membrane translocation. Overexpression of p67. phox. but not p67. phox. AD (deleting amino acid (a.a) 199 to 212) mutant, which does not support ROS production in chondrocytes, significantly enhanced chondrocyte phenotype maintenance, SOX9 expression, and AKT (S473) phosphorylation. Knockdown of p67. phox. with its specific short hairpin (sh) RNA (shRNA) abolished the suramin-induced effects. Moreover, when these cells were treated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor LY294002 or shRNA of AKT1, p67. phox. -induced COL2A1 and ACAN expression was significantly inhibited. Conclusion. Suramin could redifferentiate dedifferentiated chondrocytes dependent on p67. phox. activation, which is mediated by the PI3K/AKT/SOX9 signalling pathway. Cite this article: Bone Joint Res 2022;11(10):723–738

Abstract. Introduction. Autologous chondrocyte implantation (ACI) is a common procedure, primarily performed in active, young patients to treat knee pain and functional limitations resulting from cartilage injury. Nevertheless, the functional outcomes of ACI remain poorly understood. Thus, the aim of this systematic review was to evaluate the biomechanical outcomes of ACI. Methodology. Ovid MEDLINE, Embase, and Web of Science were systematically searched using the terms ‘Knee OR Knee joint AND Autologous chondrocyte implantation OR ACI’. Strict inclusion and exclusion criteria were used to screen publications by title, abstract, and full text. Study quality and bias were assessed by two reviewers. PROSPERO ID: CRD42021238768. Results. 28 articles including 35 ACI cohorts were included in this review. The average range of motion (ROM) was found to improve with clinical significance (>5˚) and statistical significance (p < 0.05) postoperatively: 133.9 ± 5.5˚ to 139.2 ± 4.9˚ (n=12). Knee strength significantly improved within the first two postoperative years, but remained poorer than control groups at final follow-up (n=17). No statistical differences were found between ACI and control groups in their ability to perform functional activities like the 6-minute walk test. However, peak external knee extension and adduction moments during gait were significantly poorer in ACI patients when compared to controls. Conclusion. Generally, functional outcomes improved with clinical and statistical significance following ACI. However, knee strengths and external knee moments during gait remain significantly poorer than healthy controls, particularly >2-years postoperatively. Thus, ACI patients likely require targeted strength training as part of their rehabilitation programme

Osteoarthritis (OA) is a progressive and degenerative joint disease resulting in changes to articular cartilage. In focal early OA defects, autologous chondrocyte implantation (ACI) has a 2-fold failure rate due to poor graft integration and presence of inflammatory factors (e.g. Interleukin-1β). Bone marrow derived mesenchymal stem cells (MSCs) are an alternative cell source for cell-based treatments due to their chondrogenic capacity, though in vivo implantation leads to bone formation. In vivo, chondrocytes reside under an oxygen tension between 2–7% oxygen or physioxia. Physioxia enhances MSC chondrogenesis with reduced hypertrophic marker (collagen X and MMP13) expression compared to hyperoxic conditions (20% oxygen). This study sought to understand whether implantation of physioxic preconditioned MSCs improves cartilage regeneration in an early OA defect model compared to hyperoxic MSCs. Bone marrow extracted from New Zealand white rabbits (male: 5–6 months old; n = 6) was split equally for expansion under 2% (physioxia) or 20% (hyperoxia) oxygen. Chondrogenic pellets (2 × 105 cells/pellet) formed at passage 1 were cultured in the presence of TGF-β1 under their expansion conditions and measured for their wet weight and GAG content after 21 days. During bone marrow extraction, a dental drill (2.5mm diameter) was applied to medial femoral condyle on both the right and left knee and left untreated for 6 weeks. Following this period, physioxia and hyperoxia preconditioned MSCs were seeded into a hyaluronic acid (TETEC) hydrogel. Fibrous tissue was scraped and then MSC-hydrogel was injected into the right (hyperoxic MSCs) and left (physioxia MSCs) knee. Additional control rabbits with drilled defects had fibrous tissue scrapped and then left untreated without MSC-hydrogel treatment for the duration of the experiment. Rabbits were sacrificed at 6 (n = 3) and 12 (n = 3) weeks post-treatment, condyles harvested, decalcified in 10% EDTA and sectioned using a cryostat. Region of interest was identified; sections stained with Safranin-O/Fast green and evaluated for cartilage regeneration using the Sellers scoring system by three blinded observers. Physioxic culture of rabbit MSCs showed significantly shorter doubling time and greater cell numbers compared to hyperoxic culture (∗p < 0.05). Furthermore, physioxia enhanced MSC chondrogenesis via significant increases in pellet wet weight and GAG content (∗p < 0.05). Implantation of physioxic preconditioned MSCs showed significantly improved cartilage regeneration (Mean Sellers score = 7 ± 3; ∗p < 0.05) compared to hyperoxic MSCs (Sellers score = 12 ± 2) and empty defects (Sellers score = 17 ± 3). Physioxia enhances in vitro rabbit MSC chondrogenesis. Subsequent in vivo implantation of physioxia preconditioned MSCs improved cartilage regeneration in an early OA defect model compared to hyperoxic MSCs. Future studies will investigate the mechanisms for enhanced in vivo regeneration using physioxia preconditioned MSCs

Gel-based autologous chondrocyte implantation (ACI) over the years have shown encouraging results in repairing the articular cartilage. More recently, the use of cultured mesenchymal stem cells (MSC) has represented a promising treatment option with the potential to differentiate and restore the hyaline cartilage in a more efficient way. This study aims to compare the clinical and radiological outcome obtained in these two groups. Twenty-eight consecutive symptomatic patients diagnosed with full-thickness cartilage defects were assigned to two treatment groups (16 patients cultured bone marrow-derived MSC and 12 patients with gel-type ACI). The MSC group patients underwent microfracture and bone marrow aspiration in the first stage and injection of cultured MSC into the knee in the second stage. Clinical and radiological results were compared at a minimum follow up of five years. There was excellent clinical outcome noted with no statistically significant difference between the two groups. Both ACI and MSC group showed significant improvement of the KOOS, Lysholm and IKDC scores as compared to their preoperative values and this was maintained at 5 years follow up. The average MOCART score for all lesions was also nearly similar in the two groups. The mean T2* relaxation-times for the repair tissue and native cartilage were 27.8 and 30.6 respectively in the ACI group and 28 and 29.6 respectively in the MSC group. Use of cultured MSC is less invasive, technically simpler and also avoids the need for a second surgery as compared to an ACI technique. With similar encouraging clinical results seen and the proven ability to restore true hyaline cartilage, cultured MSC represent a favorable treatment option in articular cartilage repair

Large osteochondral defects of the glenohumeral joint are difficult to treat in young, active patients. When initial non-operative treatment with physical therapy, non-steroidal anti-inflammatory medications, corticosteroid injections, and viscosupplementation fails, surgery may become an option for some patients. Traditional shoulder arthroplasty and hemiarthroplasty provide excellent function and pain relief that can be long-lasting, but these treatments are still very likely to fail during a young patient's lifetime, and results have been unsatisfactory in many younger patients. Microfracture and autologous chondrocyte implantation (ACI) have been used in the shoulder, but their use has been limited to small defects. Other techniques that incorporate soft-tissue coverage of larger osteochondral defects have the benefit of preserving bone, but have not provided consistently good results. Advanced surgical techniques have been developed including all-arthroscopic osteochondral graft resurfacing of the humerus and glenoid for the treatment of osteoarthritis. This method of ‘biological resurfacing’ of the joint without using prosthetic implants may offer potential benefits to these young patients with shoulder arthritis including faster rehabilitation, pain relief, and easier revision surgery, if necessary. Early outcomes are encouraging in many cases, but inconsistent overall, with pain relief being the most reliable indicator of patient satisfaction

Background. Structural and functional outcome of bone graft with first or second generation autologous chondrocyte implantation (ACI) in osteochondral defects has not been reported. Methods. Seventeen patients (mean age of 27±7 years, range 17–40), twelve with osteochondritis dissecans (OD) (ICRS Grade 3 and 4) and five with isolated osteochondral defect (OCD) (ICRS Grade 4) were treated with a combined implantation of a unicortical autologous bone graft with ACI (the Osplug technique). Functional outcome was assessed with Lysholm scores. The repair site was evaluated with the Oswestry Arthroscopy Score (OAS), MOCART score and ICRS II histology score. Formation of subchondral lamina and lateral integration of the bone grafts were evaluated from MRI scans. Results. The mean defect size was 4.5±2.6SD cm. 2. (range 1–9) and depth was 11.3±5SD mm (range 5–18). The pre-operative Lysholm score improved from 45 (IQR 24, range 16–79) to 77 (IQR 28, range 41–100) at 1 year (p-value 0.001) and 70 (IQR 35, range 33–91) at 5 years (p-value 0.009). The mean OAS of the repair site was 6.2 (range 0–9) at a mean of 1.3 years. The mean MOCART score was 61 ± 22SD (range 20–85) at 2.6 ± 1.8SD years. Histology demonstrated generally good integration of the repair cartilage with the underlying bone. Poor lateral integration of the bone graft on the MRI scan and a low OAS were significantly associated with a poor Lysholm score and failure. Conclusion. Osplug technique shows significant improvement of functional outcome for up to 5 years in patients with a high grade OD or OCD. This is the first report describing association of bone graft integration with functional outcome after such a procedure. It also demonstrates histological evidence of integration of the repair cartilage with the underlying bone graft. Level of Evidence. III

A prospective case control study analysed clinical and radiographic results in patients operated on with the periosteum autologous chondrocyte implantation (ACI) due to cartilage lesions on the femoral condyles over 10 years ago. 31 out of the 45 patients (3 failures, 9 non-responders, 2 others) were available for a continuous clinical (Lyshom/Tegner, IKDC, KOOS) and radiographic (Kellgren-Lawrence) follow-up at 0, 2, 5, and 10 years after the ACI procedure. The patients were sub-grouped into focal cartilage lesions (FL) – 10, osteochondritis dissecans (OCD) – 12, and cartilage lesions with simultaneous ACL reconstruction (ACL) – 9 subgroups. Lysholm, Tegner, and IKCD subjective scores revealed stable results over the period from 2 to 10 years with a significant improvement toward the pre-operative levels, but the patients had not reached their pre-injury Tegner levels. KOOS profile at 10 years was: Pain 78.6, Symptoms 78.1, Activities of daily living 82.5, Sports 56.9, and Quality of life 55.1. A 10-year IKDC knee examination classified operated knees as: 14 normal, 10 nearly normal, 5 abnormal and 2 severely abnormal. Kellgren-Lawrence scores of 2 and above were found in 10 patients (FL 5, OCD 0, and ACL 5). Seven patients in the group required an arthroscopic re-intervention (3 ACI related, 4 ACI unrelated). ACI provided safe and stable performance of operated knees over ten years. High incidence of knee osteoarthritis in FL and ACL subgroups, and low incidence in OCD patients indicate that best long performance is expected in localised low-impact cartilage lesions of young patients

Background. Treatment of cartilage defects requires in vitro expansion of human articular chondrocytes (HACs) for autologous chondrocyte implantation (ACI). During standard expansion culture (i.e. plasma osmolarity, 280 mOsm) chondrocytes inevitably lose their specific phenotype (i.e. collagen type II (COL2) expression). This de-differentiation makes them inappropriate for ACI. Physiological osmolarity (i.e. 380 mOsm) improves COL2 expression in vitro, but the underlying reason is unknown. However, an accepted key regulator of chondrocyte differentiation, transforming growth factor beta (TGFβ), is known to stimulate COL2 production. In this study we aimed to elucidate if TGFβ signaling could potentially be driving the COL2 expression under physiological culture conditions. Material and methods. After informed consent was obtained, HACs were isolated from five osteoarthritis (OA) patients and cultured in cytokine-free medium of 280 or 380 mOsm, respectively, under standard 2D in vitro conditions with or without lentiviral TGFβ2 knockdown (RNAi). Expression of TGFβ isoforms, superfamily receptors and chondrocyte marker genes was evaluated by qRT-PCR, TGFβ2 protein secretion by ELISA and TGFβ bioactivity using luciferase reporter assays. Statistical significance was assessed by a student's t-test. Results. TGFβ isoform expression was differentially altered by physiological osmolarity. Specifically, 380 mOsm increased TGFβ2 expression and protein secretion, as well as TGFβ activity. Upon TGFβ2 isoform-specific knockdown COL2 expression was induced. Physiological osmolarity and TGFβ2 RNAi also induced TGFβ1, TGFβ3 and their type I receptor ALK5. Conclusions. We showed that TGFβ2 knockdown increases COL2 expression in human osteoarthritic chondrocytes in vitro, possibly through a regulatory feedback loop involving TGFβ1, TGFβ3 induction and an increased ALK5/ALK1 ratio. This study indicates that TGFβ signalling is involved in osmolarity-induced chondrocyte marker gene expression. Pharmacological targeting of this pathway holds potential to further improve future osmolarity-mediated phenotypic stabilisation in advanced cell-based cartilage repair strategies. Level of Evidence. preclinical. Disclosure. We have nothing to disclose

Cartilage is known to have limited intrinsic repair capabilities and cartilage defects can progress to osteoarthritis (OA). OA is a major economic burden of the 21st century, being among the leading causes of disability. The risk of disability from knee OA is as great as that derived from cardiovascular disease; a fact that becomes even more concerning when considering that even isolated cartilage defects can cause pain and disability comparable to that of severe OA. Several cartilage repair procedures are in current clinical application, including microfracture, osteochondral autograft transfer, osteochondral allograft transplantation, and autologous chondrocyte implantation (ACI). Given the economic challenges facing our health care system, it appears prudent to choose procedures that provide the most durable long-term outcome. Comparatively few studies have examined long-term outcomes, an important factor when considering the substantial differences in cost and morbidity among the various treatment options. This study reviews the clinical outcomes of autologous chondrocyte implantation at a minimum of 10 years after treatment of chondral defects of the knee. Mean age at surgery was 36 ± 9 years; mean defect size measured 8.4 ± 5.5cm2. Outcome scores were prospectively collected pre- and postoperatively at the last follow up. We further analyzed potential factors contributing to failure in hopes of refining the indications for this procedure. Conclusions: ACI provided durable outcomes with a survivorship of 71% at 10 years and improved function in 75% of patients with symptomatic cartilage defects of the knee at a minimum of 10 years after surgery. A history of prior marrow stimulation as well as the treatment of very large defects was associated with an increased risk of failure

Introduction. The treatment of distal femoral cartilage defects using autologous chondrocyte implantation (ACI) and matrix-guided autologous chondrocyte implantation (MACI) is become increasingly common. This prospective 7-year study reviews and compares the clinical outcome of ACI and MACI. Methods. We present the clinical outcomes of 159 knees (156 patients) that have undergone autologous chondrocyte implantation from July 1998. One surgeon performed all operations with patients subsequently assessed on a yearly basis using 7 independent validated clinical, functional and satisfaction rating scores. Results. Modified Cincinnati, Patient Functional Outcome and Lysholm & Gilchrist clinical rating scores all showed significant improvements compared to pre-operative levels (p<0.0001). Although ACI scores are superior at one year (p<0.05) there is no significant difference between ACI and MACI at 2 years. Visual Analogue Score and Bentley Functional rating score showed significant improvements compared to pre-operative levels (p<0.0001) with ongoing yearly sequential improvement. Patient Rating and Brittberg scores, both subjective patient scores, similarly showed continuing improvements in the years following surgery. Discussion. ACI and MACI produce significant improvements in knee function when compared to pre-operative levels with continued sequential improvement in outcomes for up to seven years. The initial data suggests a superior rate of clinical improvement using the MACI technique

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

Since 1987, autologous chondrocyte implantation (ACI) has been performed in Gothenburg, Sweden in more than 1600 patients. Out of the first 442 patients operated with ACI, 153 (35%) had patella lesions and 91 (21%) had trochlea lesions. Forty two patients (9.5%) had kissing lesions of the patellofemoral joint. The aim of the study was to evaluate the current clinical status of operated patients. Lysholm and Tegner-Wallgren self-assessment questionnaires were used. The patients were requested to compare their current status to previous states and to report whether they would do the operation again. Concomitant realignment procedures of the patellofemoral joint were also recorded and preoperative scores were also assessed from the medical files. Patients were divided into groups according to the location of lesion. All the groups showed a significant improvement compared with the preoperative assessment. Over 90% of the treated patients were satisfied with the ACI and would have undergone the procedure again. It seems that correcting the coexisting background factors with realignment, stabilizing or unloading procedures is improving the results over time. Despite the initial controversy about the results and indication for ACI in patellofemoral lesions, it is clear that ACI provides a satisfactory result even for the difficult cases with concomitant patellar instability. Our study reveals preservation of the good results and of high level of patients’ activities, even 10 to 20 years after the implantation

Introduction: We report one surgeon’s experience with autologous chondrocyte implantation (ACI) for the treatment of large chondral knee defects. Method: Over a five-year period, 295 chondral knee defects in 169 patients were treated with ACI. Most patients were complex having failed other treatments. Only 4% of patients had simple condylar lesions. Patients were followed prospectively. Patients were independently evaluated by an history, clinical examination, WOMAC score, Cincinnati Knee Score (CKS), IKDC, SF-36 and patient satisfaction scores administered pre-operatively and at 12, 24, 36 and 48 months post-operatively. Results: Two hundred and sixty seven grafts (89%) were functioning well. The common causes for graft failure were poor graft incorporation and delamination, non-compliant rehabilitation and progressive osteoarthritis. Periosteal hypertrophy was present in 20% requiring arthroscopic debridement. All outcome measures improved significantly with time. Conclusion: In a complex group of patients ACI showed encouraging results in the short term

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. Results. Patients were divided into 2 groups; Group A were patients with no evidence of OA (n=72) and Group B were patients with OA (n=164). In group A, two patients required total knee replacement (TKR) or unicondylar knee replacement (UKR) and 3 required high tibial osteotomy (overall revision rate 6.9%). In group B, 34 patients required patello-femoral replacement, or UKR or TKR and 17 patients required osteotomy (overall revision rate 31.1%). This difference was significant (p < 0.01). At latest follow up, the mean MCS was significantly higher in Group A (72.5 versus 51.8, p < 0.01). Conclusions. Patients with early radiographic of evidence of OA are unlikely to gain maximum benefit from ACI. The results suggest that ACI does not prevent patients from progressing in their arthritic process and hence requiring joint replacement

Background. Autologous chondrocyte implantation (ACI) and mosaicplasty (MP) are two methods of repair of symptomatic articular cartilage defects in the adult knee. This study represents the only long-term comparative clinical trial of the two methods. Methods. A prospective, randomised comparison of the two modalities involving 100 patients with symptomatic articular cartilage lesions was undertaken. Patients were followed for ten years. Pain and function were assessed using the modified Cincinnati score, Bentley Stanmore Functional rating system and visual analogue scores. ‘Failure’ was determined by pain, a poor outcome score and arthroscopic evidence of graft disintegration. Results. Patients had a mean age at index operation of 31. There was a long mean pre-op duration of symptoms of seven years and the defects had an average of 1.5 operations (excluding arthroscopy) to the articular cartilage lesion prior to the cartilage repair surgery. The aetiology of the articular cartilage defects was mainly trauma; some patients had osteochondritis dissecans or chondromalacia patellae. Five patients were lost to follow-up. A total of 23 out of 42 mosaicplasty patients failed, 10 out of 58 ACI patients failed (p<0.001). Most patients did well for the first two years when there was a steep failure of mosaicplasty patients, after which the failure rate was more constant. There was a low steady failure rate of ACI over the 10 years. Older patients treated by ACI did worse than younger patients; age was less of a prognostic indicator in MP. Patients irrespective of gender or aetiology of the defect fared better with ACI than MP. Conclusion. At ten years, patients who underwent cartilage repair using ACI fared significantly better than those who underwent mosaicplasty

Aims: Damage to articular hyaline cartilage may predispose to earlyonset osteoarthritis. Hyaline cartilage has not been shown to spontaneously regenerate and previous methods of stimulating repair have often yielded þbrocartilage. Autologous chondrocyte implantation (ACI) offers the potential for hyaline cartilage repair. Methods: A prospective study of 31 patients undergoing ACI using the chondrogide membrane. Patients were assessed clinically using validated knee scores pre-operatively and post-operatively at yearly intervals. Arthroscopy was carried out at one year post implantation and a biopsy of the transplanted area was sent for histological examination. Results: 32 knees (including 2 bilateral) were reviewed clinically at one year, and 15 were reviewed at 2 years. 33 defects (including 2 defects in one knee) were assessed arthroscopically at one year. Only one repair showed hypertrophy at one-year arthroscopy, and 8 had poor integration. Hyaline-like cartilage was demonstrated in 70% of the repairs. Patients showed improvement in the Verbal Numerical Pain scores and in the Lysholm and Gillquist score. Conclusions: In our series, the use of chondrogide membrane shows a low incidence of hypertrophy when compared to periosteum. Improvement in knee scores was statistically signiþcant at one and two years

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. 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 and 50% of MACI grafts. Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in biopsies of 56.3% of the ACI-C grafts and 30% of the MACI grafts after 2 years. Conclusion. At this stage of the trial we conclude that the clinical, arthroscopic and histological outcomes are comparable for both ACI-C and MACI

Introduction: The treatment of distal femoral cartilage defects using autologous chondrocyte implantation (ACI) and matrix-guided autologous chondrocyte implantation (MACI) is become increasingly common. This prospective 7-year study reviews and compares the clinical outcome of ACI and MACI. Methods: We present the clinical outcomes of 159 knees (156 patients) that have undergone autologous chondrocyte implantation from July 1998. One surgeon performed all operations with patients subsequently assessed on a yearly basis using 7 independent validated clinical, functional & satisfaction rating scores. Results: Modified Cincinnati, Patient Functional Outcome and Lysholm & Gilchrist clinical rating scores all showed significant improvements compared to pre-operative levels (p< 0.0001). Although ACI scores are superior at one year (p< 0.05) there is no significant difference between ACI and MACI at 2 years. Visual Analogue Score and Bentley Functional rating score showed significant improvements compared to pre-operative levels (p< 0.0001) with ongoing yearly sequential improvement. Patient Rating and Brittberg scores, both subjective patient scores, similarly showed continuing improvements in the years following surgery. Discussion: ACI and MACI produce significant improvements in knee function when compared to pre-operative levels with continued sequential improvement in outcomes for up to seven years. The initial data suggests a superior rate of clinical improvement using the MACI technique

Purpose. Osteochondral lesions (OCL) of the talus remain a challenging therapeutic task to orthopaedic surgeons. Several operative techniques are available for treatment, e.g. autologous chondrocyte implantation (ACI), osteochondral autograft transfer system (OATS), matrix-induced autologous chondrocyte implantation (MACI). Good early results are reported; however, disadvantages are sacrifice of healthy cartilage of another joint or necessity of a two-stage procedure. This case describes a novel, one-step operative treatment of OCL of the talus utilizing the autologous matrix-induced chondrogenesis (AMIC) technique in combination with a collagen I/III membrane. Method. 20 patients (8 female, 12 male; mean age 36, range 17–55 years) were assessed in our outpatient clinic for unilateral OCL of the talus. Preoperative assessment included the AOFAS hindfoot scale, conventional radiography, magnetresonancetomography (MRI) and SPECT-CT. Surgical procedure consisted of debridement of the OCL, spongiosa plasty from the iliac crest and coverage with the I/III collagen membrane (Chondrogide, Geistlich Biomaterials, Wolhusen, Switzerland). Clinical and radiological followup was performed after one year. Results. The mean preoperative AOFAS hindfoot scale was poor with 63.1 points (SD 19.6). At one year followup the score improved significantly (p<0.01) to 86 points (SD 12). At one year followup conventional radiographs showed osseous integration of the graft in all cases. MRI at one year showed intact cartilage covering the lesions in all cases. Conclusion. The initial results of this ongoing study are encouraging. The clinical and radiological results at one year followup are comparable with the results of ACI, OATS and MACI. The AMIC procedure is a readily available, economically efficient, one step surgical procedure. No culturing after chondrocyte harvesting or destruction of viable cartilage is necessary

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