Introduction. The purpose of this study is to evaluate the early functional outcome and activity level in athletes and soldiers with large full thickness cartilage defects of the knee that underwent either ‘classic’ autologous chondrocyte implantation using periosteal flap coverage (ACI-P) or 3-D matrix-assisted chondrocyte implantation (ACI-M). Methods. Between April 2002 and January 2004, 19 patients (15 male, 4 female, average age 32.2 years) with 22 full-thickness cartilage defects in 19 knees were treated with ACI in our centre. The mean post-injury interval was 39.8 months whereas 17 (89.5%) patients had undergone at least one surgical procedure before ACI. The average defect size was 6.54 cm. 2. (located in MFC:7, LFC:7 or trochlear:2 while 3 patients had bifocal lesions in both LFC and TRC). Novocart. ¯. cultured chondrocytes with periosteal flap coverage were used in 11 patients and Novocart-3D. ¯. cell impregnated collagen patch in 8. The functional outcome was evaluated with IKDC form, Tegner activity scale and Lysholm score after a mean follow-up period of 26.5 months. Results. The average IKDC and Lysholm scores were improved from 39.16 and 42.42 pre-operatively to 62.4 and 69.4 at the latest follow-up respectively. The mean Tegner activity scale was 8.73 before injury, 3.63 pre-operatively and 5.21 at the latest follow-up. There was no statistically significant difference between the two groups regarding the clinical outcome and the overall athletic or military performance. Second-look arthroscopy was performed in 11 (57.8%) patients due to persistent pain and/or mechanical symptoms. Generally, the ACI site showed adequate graft integration except for one partial failure. Conclusions. The early results of ACI in high-performance athletes and professional soldiers are not as good as other recent studies suggest. Motivational issues during prolonged rehabilitation, patient age and very large defects may influence early results in this select group of patients

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

Statement of Purpose We describe the donor site morbidity of hyaline cartilage biopsy from the trochlea of the knee when used for ACI in the ankle joint. Methods We studied 12 patients who received a two stage ACI procedure on the talus, performed by three consultant surgeons. The first stage involved knee arthroscopy and harvest of cartilage for culture and stage two the transplantation of a chondrocyte culture to the ankle joint. During the first stage knee arthroscopy using a superolateral approach, the cartilage specimens were taken from a minor load bearing area of either the central or superolateral trochlea using a 5mm gouge. Clinical outcomes were assessed using a patient satisfaction score and the Lysholm knee score, taken both pre- and post- operatively at 3 months and annually thereafter. Results The mean age of the patient group was 42. The patient satisfaction questionnaires showed 11 patients to be ‘pleased’ or ‘extremely pleased’ with their ACI procedure which was sustained in the patients with up to four years follow up. The mean Lysholm score preoperatively was 98/100. Postoperatively eight patients had a reduced score (mean reduction 14) at twelve months follow up. In those patients with new knee symptoms at one year, analysis of the Lysholm score components showed the Locking and Limp categories to be the most frequent cause of a reduced score. Two patients had repeat knee arthroscopy at 18 months and 2 years postoperatively for symptoms of catching, anterior knee pain and swelling. Discussion The Lysholm knee score has components which may be affected by ipsilateral joint problems, which contribute to 20% of the overall score. However those patients with an abnormal Lysholm knee score postoperatively have gained an improved Mazur ankle score since their ACI. The procedure of cartilage harvest from the trochlea of the knee has an associated donor site morbidity which is present at one year. Ninety two percent of patients were pleased or extremely pleased with their ACI procedure, despite the requirement of surgery on their knee and it would seem that the amount of early knee morbidity these patients experience is outweighed by the improvement in symptoms in the treated joint. Ideally to optimise cartilage repair less morbid techniques to obtain cartilage need to be identified or alternatively mesenchymal stem cells could be used as an alternative source, which has already had limited success in the knee and might also be applied to other joints

Marrow stimulation techniques such as drilling or microfracture are first-line treatment options for symptomatic cartilage defects. Common knowledge holds that these treatments do not compromise subsequent cartilage repair procedures with autologous chondrocyte implantation (ACI). We present our experience with ACI after prior marrow stimulation. This study reviewed prospectively collected data for the first 321 consecutive patients treated at our institution with ACI for full-thickness cartilage defects that have reached more than 2 years of follow-up. Patients were grouped based on whether they had undergone prior treatment with a marrow stimulation technique. Outcomes were classified as complete failure if more than 25% of a grafted defect area had to be removed in later procedures due to persistent symptoms. This includes treatment with revision ACI, allograft transplantation, partial or total knee replacement. 522 defects in 321 patients (325 joints) were treated with ACI. Patient average age was 35 (13–60), there were 185 men and 136 women, with a follow-up of 2–12 Years. On average, there were 1.7 lesions per patient (range, 1–5) with a transplant area of 4.8 cm2 per lesion and 8.1 cm2 per knee. 111 of these joints had previously undergone surgery that penetrated the subchondral bone: microfracture (n=25), abrasion chondroplasty (n=33), and drilling (n=53). 214 joints had no prior treatment that affected the subchondral bone and served as control. Within the marrow stimulation group, there were 27 (24%) failures compared with 17 (8%) failures in the control group. In our review of 321 patients, defects that had prior treatment affecting the subchondral bone failed at a rate 3 times that of non-treated defects. These data demonstrate that marrow stimulation techniques have a strong negative effect on subsequent cartilage repair, and should be used judiciously in larger cartilage defects that could require future treatment with ACI

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

Autologous chondrocyte implantation is now a recognised treatment for patients with knee pain secondary to articular cartilage defects. The initial technique involving periosteum as the cover for the implanted cells (ACI-P) has been modified to the use of a type I/III collagen membrane (ACI-C). Matrix-induced Autologous Chondrocyte Implantation (MACI) is a technique in which autologous donor chondrocytes are implanted onto the collagen membrane and then fixed into the defect with fibrin glue. We performed a prospective randomised comparison of 247 patients (126 ACI and 121 MACI). Patients' pain and function were assessed with mean follow-up of 42 months. Function was measured using the Modified Cincinnati and Stanmore Scoring systems. Arthroscopic assessment was by the ICRS classification. The influence of the size and site of the lesion, sex, age and previous knee surgery on the results was analysed. The Modified Cincinnati score showed a mean 17.5 point rise from pre-operative scores in the ACI group and 19.6 point rise in the MACI group. Pain, measured using the Visual Analogue Score, showed an improvement in both arms of the trial. Both chondrocyte implantation methods showed improvement in 86% of patients clinically and arthroscopically, with excellent and good results in 50% and fair results in 30% of patients. 20% of patients showed no improvement in function but none were worse. There were no serious complications. Limited histological analysis showed hyaline cartilage in a higher but non-significant proportion of ACI-C cases. With over 11 years' experience in the use of both forms of cartilage implantation we have established more precisely the indications for chondrocyte implantation. Although MACI is technically a more attractive option in most cases, because of ease and speed of the procedure, longer term follow-up is required to assess the longevity of ACI-C and MACI and the effect on prevention of ‘early-onset’ Osteoarthritis

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

Introduction & Aims: To assess the efficacy of periosteal ACI (P-ACI) for articular cartilage lesions of the knee, a study was carried out on patients with minimum 5 year follow up including clinical assessment, second look arthroscopy when indicated clinically and MRI evaluation. Method: Between October 2000 and April 2003 the author carried out P-ACI on 164 patients. Of these 104 patients (106 knees – 145 lesions) could be included in this study. There were 106 single, 35 double and three triple lesions. Seventy-eight lesions were considered traumatic, 63 degenerative and 4 OCD. Previous surgery was frequent. Arthroscopic debridement (78), meniscal surgery (52), arthroscopic micro-fracture (19), ACL (12), lateral release (6), UTO (4) and extensor realignment (2). Results: Results were assessed according to the ICRS cartilage repair evaluation package. Significant improvement was seen in average Activity Level, Objective Knee Examination, Physical Component Score and Mental Component Score. IKDC subjective assessment improved by an average of 21 points. There were 6 failures, 5 coming to TKR in the course of this study and 1 with advanced degenerative change requiring TKR. “Second look” arthroscopy was carried out on 75 knees with 102 lesions at average 26 months from implantation for graft hypertrophy/extrusion presenting as painless mechanical symptoms (24), partial or complete periosteal patch loss (8), partial loss of graft (9), adjacent loss of host cartilage (4) and total loss of graft (3). “Third look” arthroscopy occurred in 35 knees with 35 lesions at average 44.4 months from index implantation for partial loss of graft (8), adjacent host cartilage lesion (8), hypertrophy or periosteal patch detachment (6), new remote cartilage lesion (4) and total loss of graft (2). “Fourth look” arthroscopy was carried out on 9 knees with 12 lesions at average 59 months from index implantation for adjacent host cartilage loss (4), partial loss of graft (3) and advancing degenerative change (3). Conclusion: This study supports the efficacy of P-ACI for appropriate articular cartilage lesions of the knee with good clinical outcome and satisfactory repair when assessed arthroscopically Subsequent arthroscopic surgery was frequently required, predominantly related to the periosteal patch in the first year, after which adjacent host cartilage lesions, remote new cartilage lesions and partial loss of the graft became more Significant

Articular cartilage implantation (ACI) and associated procedures (MACI = Matrix-assisted cartilage implantation) are now established treatments for osteochondral defects in the knee. The quality of repair in terms of histological appearance is frequently not known, whilst the correlation of histology results with functional outcomes remains undefined. Histological data of the quality of the repair tissue is sparse and a precise classification proved difficult.

This was a single-centre, prospective study. Over 12 years (1998-2010) 406 patients that underwent articular cartilage implantation procedures at our institution (ACI = 170, MACI = 205) had biopsies taken at the 1-2 year interval, in order to assess whether these contained ‘hyaline-like’ cartilage, ‘mixed hyaline-like with fibrocartilage’, fibrocartilage or fibrous tissue alone.

Histological sections of the biopsies were prepared and stained with haematoxylin, eosin and proteoglycan stains and viewed under polarised light. All biopsies were studied by a single histopathologist in a specialist, dedicated musculoskeletal laboratory.

All patients were assessed by the Cincinnati, Bentley and Visual Analogue scores both pre-operatively and at the time of the review.

The findings revealed that 56 patients healed with ‘hyaline-like’ cartilage (14.9%), 103 with ‘mixed’ (27.5%), 179 with fibrocartilage (47.7%) and 37 with fibrous tissue (9.9%).

These findings showed that 42.4% of defects were filled with ‘hyaline-like’ or ‘mixed’ cartilage, with 70% of these achieving a ‘fair’ to ‘excellent’ functional outcome. This was also observed in the fibrocartilage group, where 72% achieved similar results. Predictably 89% of the patients that healed by fibrous tissue had a poor functional outcome.

This study shows that 71% of patients whose osteochondral defects healed by either ‘hyaline-like’, ‘mixed’ or fibrocartilage experienced an improvement in the function. In contrast, only 11% of the patients whose defects filled with fibrous tissue, showed some functional improvement. Additionally, this data indicates the advantage of biopsies in assessing the overall results of cartilage implantation procedures.

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.

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

Stratification is required to ensure that only those patients likely to benefit, receive Autologous Chondrocyte Implantation (ACI); ideally by assessing a biomarker in the blood. This study aimed to assess differences in the plasma proteome of individuals who respond well or poorly to ACI. Isobaric tag for relative and absolute quantitation (ITRAQ) mass spectrometry and label-free proteomics analyses were performed in tandem as described previously by our group (Hulme et al., 2017; 2018; 2021) using plasma collected from ACI responders (n=10) compared with non-responders (n=10) at each stage of surgery (Stage I, cartilage harvest and Stage II, cell implantation). iTRAQ using pooled plasma detected 16 proteins that were differentially abundant at baseline in ACI responders compared with non-responders (n=10) (≥±2.0 fold; p<0.05). Responders demonstrated a mean Lysholm (patient reported functional score from 0–100) improvement of 33±13 and non-responders a mean worsening of −13±13 points. The most pronounced plasma proteome shift was seen in response to Stage I surgery in ACI non-responders, with 48 proteins being differentially abundant between the two surgical procedures. We have previously noted this marked shift in response to initial surgery in the SF of ACI non-responders, several of these proteins were associated with the Acute Phase Response. One of these proteins, clusterin, could be confirmed in patients’ plasma using an independent immunoassay using individual samples. Label-free proteomic data from individual samples identified only cartilage acidic protein-1 (known to associate with osteoarthritis progression) to be significantly more abundant at Stage I in the plasma of non-responders. This study indicates that proteins can be identified within the plasma that have potential use in ACI patient stratification. Further work is required to validate the findings of this discovery-phase work in larger ACI cohorts

The objectives of the study were to investigate demographic, injury and surgery/treatment-associated factors that could influence clinical outcome, following Autologous Chondrocyte Implantation (ACI) in a large, “real-world”, 20 year longitudinally collected clinical data set. Multilevel modelling was conducted using R and 363 ACI procedures were suitable for model inclusion. All longitudinal post-operative Lysholm scores collected after ACI treatment and before a second procedure (such as knee arthroplasty but excluding minor procedures such as arthroscopy) were included. Any patients requiring a bone graft at the time of ACI were excluded. Potential predictors of ACI outcome explored were age at the time of ACI, gender, smoker status, pre-operative Lysholm score, time from surgery, defect location, number of defects, patch type, previous operations, undergoing parallel procedure(s) at the time of ACI, cell count prior to implantation and cell passage number. The best fit model demonstrated that for every yearly increase in age at the time of surgery, Lysholm scores decreased by 0.2 at 1-year post-surgery. Additionally, for every point increase in pre-operative Lysholm score, post-operative Lysholm score at 1 year increased by 0.5. The number of cells implanted also impacted on Lysholm score at 1-year post-op with every point increase in log cell number resulting in a 5.3 lower score. In addition, those patients with a defect on the lateral femoral condyle (LFC), had on average Lysholm scores that were 6.3 points higher one year after surgery compared to medial femoral condyle (MFC) defects. Defect grade and location was shown to affect long term Lysholm scores, those with grade 3 and patella defects having on average higher scores compared to patients with grade 4 or trochlea defects. Some of the predictors identified agree with previous reports, particularly that increased age, poorer pre-operative function and worse defect grades predicted poorer outcomes. Other findings were more novel, such as that a lower cell number implanted and that LFC defects were predicted to have higher Lysholm scores at 1 year and that patella lesions are associated with improved long-term outcomes cf. trochlea lesions

Abstract. Purpose. Stratification is required to ensure that only patients likely to benefit, receive Autologous Chondrocyte Implantation (ACI). At Stage I (SI), healthy cartilage is harvested from the joint and chondrocytes culture expanded before being implanted into a chondral/osteochondral defect at Stage II (SII). In ACI non-responders, there is a marked shift in the profile and abundance of proteins detectable in the synovial fluid (SF) at SII, many being associated with an acute phase response (APR). However, clinical biomarkers are easier to measure in blood than SF, so we have now performed this investigation in plasma. Methods. Isobaric tag for relative and absolute quantitation mass-spectrometry was used to assess the proteome in plasma pooled from ACI responders (mean Lysholm improvement of 33, n=10) or non-responders (mean: −13 points, n=10), collected at SI or SII surgeries. Interactome networks were generated using STRING. Plasma proteome data were compared to matched SF data, previously analysed, to identify any proteins that changed across the fluids. Clusterin concentration was quantitated (ELISA; Biotechne). Results. The most pronounced plasma proteome shift was seen in response to SI surgery in ACI non-responders (50 proteins; ±2.0FC; p<0.05). An interactome network was generated based on these proteins. Functions associated with this network included complement and coagulation cascade (FDR= 5.99×10-. 25. ). Sixteen matched proteins were differentially abundant between SI and SII in both the SF and plasma, 75% of which were APR associated proteins. These included clusterin, which was confirmed by ELISA (p=0.001). Conclusions. Changes in APR signalling between SI and SII surgeries in non-responders to ACI can be identified in plasma and SF. The APR is the body's first systemic response to trauma and surgery. Our data indicate that ACI non-responders may have a greater innate response to initial surgery, which is detectable in both their SF and plasma

Abstract. Objectives. Meniscus allograft and synthetic meniscus scaffold (Actifit. ®. ) transplantation have shown promising outcomes for symptoms relief in patients with meniscus deficient knees. Untreated chondral defects can place excessive load onto meniscus transplants and cause early graft failure. We hypothesised that combined ACI and allograft or synthetic meniscus replacement might provide a solution for meniscus deficient individuals with co-existing lesions in cartilage and meniscus. Methods. We retrospectively collected data from 17 patients (16M, 1F, aged 40±9.26) who had ACI and meniscus allograft transplant (MAT), 8 patients (7M, 1F, aged 42±11) who underwent ACI and Actifit. ®. meniscus scaffold replacement. Other baseline data included BMI, pre-operative procedures and cellular transplant data. Patients were assessed by pre-operative, one-year and last follow-up Lysholm score, one-year repair site biopsy, MRI evaluations. Results. In the MAT group, the final post-operative evaluation was 7±4.5 years. The mean pre-operative Lysholm score was 49±17, rose to 66.6±16.4 1 year post-op and dropped to 58±26 at final evaluation. Four of the 17 patients had total knee replacements (TKRs) at average 6.4 years after treatment. In the Actifit. ®. group, the final post-operative assessment was 5.6±2.7years. The pre-operative Lysholm score was 53.7±21.3, increasing to 72.8±15.2 at 1 year and 70.4±27.6 at final clinical follow-up. None of the patients in the Actifit® group had received TKRs. Conclusions. Both MAT and Actifit. ®. groups were effective in improving patients symptoms and knee function according to one-year post-operative assessments. However, the knee function of patients in MAT group dropped at final follow-up, whereas the Actifit® group maintained their knee function. These preliminary findings warrant further investigations, to include more patients and alongside comparisons to ACI alone and allograft/Actifit. ®. alone as comparator groups before accurate conclusions may be drawn on the comparative efficacy of each technique. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

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

Introduction. The management of early OA in young patients with joint preservation techniques utilizing cartilage repair remains challenging and a suitable treatment remains unclear. The management of bipolar chondral lesions in the patello-femoral (PF) and in the tibio-femoral (TF) compartment with cartilage repair is especially troublesome. The purpose of this study was to evaluate the clinical outcomes and survivorship after ACI for the treatment of bipolar chondral lesions in the PF and TF compartment. Methods. This was an IRB approved, prospectively collected case series, level 4 study. We evaluated 115 patients. 58 patients who had ACI for the treatment of symptomatic bipolar chondral lesions in the PF compartment and 57 in the TF compartment with a minimum 2-year follow up. A single surgeon performed all the surgeries between October 1995 and June 2014. In the PF group, all 58 patients (60 knees; mean age, 36.6 years) were included, and for the TF group one patient did not return for follow-up, 56 patients (58 knees) were included. For the PF group, an average size of the patella and trochlea lesions were 5.6 ± 2.7 cm2 and 4.2 ± 2.8 cm2, respectively. For the TF group, an average of 3.1 lesions per knee were treated, representing a total surface area of 16.1 cm2 (range, 3.2 – 44.5 cm2) per knee. Patients were evaluated with the modified Cincinnati Knee Rating Scale, Visual Analogue Scale, Western Ontario and McMaster Universities Osteoarthritis Index, and the Short Form 36. Patients also answered questions regarding self-rated knee function and satisfaction with the procedure. Standard radiographs were evaluated for progression of OA. Results. Patients did well for bipolar ACI in both compartments. In the PF compartment overall, the survival rate was 83% and 79% at 5 and 10 years, respectively. Of the 49 (82%) knees with retained grafts, all functional scores significantly improved postoperatively with a very high satisfaction rate (88%) at a mean of 8.8 years after ACI (range, 2 – 16 years). Outcomes for 11 patients were considered as failures at a mean of 2.9 years. In the TF group, the overall survival rate was 80% at 5 years and 76% at 10 years. Significantly better survival rate in patients with the use of collagen membrane than periosteum (97% vs. 61% at 5 years, P = 0.0014) was found. Of 46 knees with retained grafts, all functional scores significantly improved postoperatively with a very high satisfaction rate (85%) at a mean of 8.3 years after ACI (range, 2–20 years). Outcomes for 12 patients were considered as failures at a mean of 4.1 years. Of them, 9 patients were converted to a partial or total knee arthroplasty at a mean of 4.4 years. Two patients had revision ACI at 5 and 17 months. The other one patient did not require a revision surgery. At the most recent follow-up for both groups there was no radiographic progression to OA. Conclusions. Our study showed that ACI for the treatment of bipolar chondral lesions in the PF and TF compartments provided successful clinical outcomes in patients with retained grafts and could possibly prevent or delay OA progression. The best results in the PF joint are as primary repairs and not after failed osteotomy or cartilage repair with a 91% 10-year survival. Collagen membrane is more encouraging than periosteum for bipolar lesions in both the PF and TF compartments. ACI could be an adequate salvage procedure for bipolar chondral lesions in the TF compartment for the relatively young arthritic patient who wishes to avoid an arthroplasty

Background. Microfracture (MF) and Autologous Chondrocyte Implantation (ACI) are used to repair symptomatic condylar cartilage defects (grade II-IV Outerbridge). Superiority of ACI to MF is still debated. The aim of the study was to conduct a systematic literature review, compare superiority of ACI versus MF in a meta-analysis and investigate the correlation between patient age and outcome of both treatments. Methods. Extended literature search was conducted (papers from January 2001 to present), looking at patient characteristics, pre- and post-operative scores and cartilage repair assessment evaluation. Methodological quality was verified through modified Coleman score and assessment bias. A fixed-effect meta-analysis was conducted, comparing post-operative standardised mean differences between ACI and MF. Pearson correlation coefficient between post-operative score and age was calculated against ACI and MF. Results. of 490 studies systematically analysed, 8 met the inclusion criteria, accounting for 255 patients treated with ACI and 259 with MF. Overall mean postoperative scores were 81.38±8.31 for ACI and 74.9±7.0 for MF, with no significant difference (p=0.13). The average modified Coleman score of the studies was 82.6, with low bias among them. The meta-analysis displayed an overall effect estimate of 0.3 favouring ACI treatment versus MF (95%CI=0.12–0.48, P=0.001). Significant heterogeneity was although observed (I2>70%). Pearson correlation coefficient calculated between mean post-operative score and mean age, surprisingly failed to indicate clear correlation for ACI (r=0.11) and MF (r=0.18) respectively. Conclusions. Minor statistically significant superiority of ACI intervention versus MF in knee cartilage repair was found, together with high levels of heterogeneity, halting the possibility to make full recommendation of ACI versus MF. Level of Evidence. Ia (systematic review and meta-analysis)

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)

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

Articular cartilage injury has a high prevalence in elite and recreational athletes. Articular cartilage repair remains a challenge due to cost effectiveness and clinical effectiveness issues. There are now several effective technologies and it is possible to return to competitive sports following many of the procedures available. The durability of repair tissue is variable and there remains extensive growth in the Scientific world. Evolving cartilage restoration technologies focus on increasing cartilage quality and quantity, while optimising surgery and rehabilitation. In UK ACI has undergone extensive cost effectiveness analysis and the in-depth review has shown that ACI is cost effective compared to microfracture. ACI is indicated for lesions >2cm sq but NICE has considered that it is not indicated for problems after microfracture. This presentation details the various options available to surgeons and examines the cost effectiveness

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

Purpose: To assess costs and health status outcomes following ACI and mosaicplasty used to treat chondral knee defects (1). Methods: Patients received ACI or mosaicplasty at the Royal National Orthopaedic Hospital between 1997 and 2001, or, were on a waiting list for ACI. Resource use per patient was collected to two years post-operatively. A postal questionnaire collected sociodemographic characteristics, knee-related (Modified Cincinnati Knee Rating System) and general health status (EQ-5D). Results: 53 ACI, 20 mosaicplasty and 22 patients waiting for ACI participated in this study. The average cost per patient was higher for ACI (£10,600: 95%CI £10,036-£11,214) than for mosaicplasty (£7,948: 95%CI £6,957-£9,243). Estimated average EQ-5D social tariff improvements for QALYs (quality adjusted life years) were 0.23 for ACI and 0.06 for mosaicplasty. Average costs per QALY were: £23,043 for ACI and £66,233 for mosaicplasty. The ICER (incremental cost effectiveness ratio) for providing ACI over mosaicplasty was £16,349. Post-operatively, ACI and mosaicplasty patients (combined) experienced better health status than patients waiting for ACI. ACI patients tended to have better health status outcomes than mosaicplasty patients, although this was not statistically significant. Conclusions: Average costs were higher for ACI than for mosaicplasty. However, both the estimated cost per QALY and ICER fell beneath an implicit English funding threshold of £30,000 per QALY. To our knowledge this is the first study to compare the costs and utility of ACI with alternative ‘best’ treatments for people with chondral knee problems. Prospective studies are required to confirm these results

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.

Introduction. Autologous chondrocyte implantation (ACI) is contra-indicated in a joint rendered unstable by a ruptured anterior cruciate ligament (ACL). We present our experience of ACI repair with ACL reconstruction. Methods. Patients underwent arthroscopic examination and cartilage harvesting of the knee. A second operation was undertaken approximately six weeks later to repair the ruptured ACL with hamstring graft or Bone patella-Bone (BPB) and to implant the chondrocytes via formal arthrotomy. Three groups were assessed: Group 1: Simultaneous ACL Reconstruction and ACI; Group 2: Previous ACL Reconstruction with subsequent ACI repair; Group 3: Previously proven partial or complete ACL rupture, deemed stable and not treated with reconstruction with ACI procedure subsequently. Patients then underwent a graduated rehabilitation program and were reviewed using three functional measurements: Bentley functional scale, the modified Cincinnati rating system, and pain measured on a visual analogue scale. All patients also underwent formal clinical examination at review. Results. Those who underwent simultaneous ACL Reconstruction and ACI had a 47% improvement in Bentley functional scale, 36% improvement in visual analogue score and 38% improvement in the modified Cincinnati rating system. This is in contrast to only a 15% improvement in the modified Cincinnati rating system, 30% improvement in Bentley functional scale, and 32% improvement in visual analogue score in patients who had ACI repair after previous ACL reconstruction. 68% of patients who had the procedures simultaneously rated their outcome as excellent/good and 27% felt it was a failure. In contrast 38% of patients rated their outcome as a failure if they had ACI repair without reconstruction of ACL rupture. Conclusion. Symptomatic cartilage defects and ACL deficiency may co-exist in many patients and represent a treatment challenge. Our results suggest that a combined ACL and ACI repair is a viable option in this group of patients and should reduce the anaesthetic and operative risks of a two-stage repair. Patients with complete rupture of ACL despite being deemed stable performed poorly at review and our study suggests all complete ruptures regardless of stability should be treated with a reconstruction when performing an autologous chondrocyte implantation

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

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

The results for autologous chondrocyte implantation (ACI) in the treatment of osteochondral defects in the knee are encouraging. At present, two techniques have been described to retain the chondrocyte suspension within the defect. The first involves using a periosteal flap harvested from the distal femur and the second involves using a type I/III collagen membrane. To the authors' knowledge there are no comparative studies of these two techniques in the current literature. A total of 68 patients with a mean age of 30.52 years (range 15 to 52 years) with symptomatic articular cartilage defects were randomised to have either ACI with a periosteal cover (33 patients) or ACI with a type I/III collagen cover (35 patients). The mean defect size was 4.54 cm. 2. (range 1 to 12 cm. 2. ). All patients were followed up at 24 months. A functional assessment using the Modified Cincinnati score showed that 74% of patients had a good or excellent result following the ACI with collagen cover compared with 67% after the ACI with periosteum cover at 2 years (p>0.05). Arthroscopy at 1 year also demonstrated similar results for both techniques. However, 36.4% of the periosteum covered grafts required shaving for hypertrophy compared with 1 patient for the collagen covered technique. This prospective, randomised study has shown no statistical difference between the clinical outcome of ACI with a periosteal cover versus ACI with a collagen cover at 2 years. A significant number of patients who had the ACI with periosteum technique required shaving of a hypertrophied graft within the first year of surgery. We conclude that there is no advantage in using periosteum as a cover for retaining the chondrocytes within an osteochondral defect; as a result we advocate the use of an alternative cover such as a porcine-derived, type I/III collagen membrane

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

Introduction. Autologous Chondrocyte Implantation (ACI) is an effective surgical treatment for chondral defects. ACI involves arthrotomy for cell implantation. We describe the development of an intra-articular injection of cultured MSC, progressing from in-vitro analysis, through animal model, clinical and radiological outcome at five years follow up. Materials and Methods. We prospectively investigated sixteen patients with symptomatic ICRS grade III and IV lesions. These patients underwent cartilage repair using cultured mesenchymal stem cell injections and are followed up for five years. Results. Statistically significant clinical improvement was noted by two years and was sustained for five years of the study. At five years, mean Lysholm score was 80, compared to 44 pre-operatively. Symptomatic KOOS improved to 88 from 55. Subjective IKD Calso showed improvement from 42 to 76. On morphological MRI MOCART score was 76 and qualitative MRI showed the mean T2relaxation-times were 28 and 31 for their pair tissue and native cartilage respectively. Discussion. Cultured MSC provides a good number of uncommitted stem cells to the previously prepared chondral defects of the knee by “homing on” phenomenon. Cultured cells, suspended in serum can be delivered by an intra-articular injection. Conclusion. Use of cultured MSC is less invasive, avoids complications associated with arthrotomy, compared to ACI technique. Good clinical results were found to be sustained at five years of follow-up with a regenerate that appears like surrounding native cartilage. The use of Cultured Mesenchymal Stem Cells (MSC) has represented a promising treatment to restore the articular cartilage

Background: Autologous chondrocyte implantation (ACI) was introduced over 15 years ago as a treatment for full-thickness chondral defects in the knee. Current understanding of ACI graft morphology and maturation in humans is limited. The aims of this study were determine the incidence of hyaline-like repair following ACI, and to clarify the relationship between repair morphology and clinical outcome. Methods: A retrospective review of 194 ACI graft biopsies from 180 patients, and their clinical outcome was conducted. 154 Biopsies were performed 1 year after implantation and 40 biopsies were performed at 2 years. Three techniques of ACI implantation were used; Collagen covered ACI (ACI-C), periosteum covered ACI (ACI-P) and Matrix-Induced ACI (MACI). Results: At 1 year, hyaline repair tissue was found in 48 (53%) ACI-C grafts, 7 (44%) ACI-P grafts, and 12 (36%) MACI grafts. The frequency of hyaline tissue found in biopsies performed at 2 years (84%) was significantly higher than those performed at 1 year (48.6%), p=0.0001, suggesting that grafts continue to remodel after the first year post implantation. Clinical outcomes during the first two postoperative years did not vary according to repair morphology type, though hyaline repair was associated with better clinical outcomes beyond 2 years; At 1 year, good to excellent clinical scores were observed in 29 (78.4%) patients with hyaline-like repair, 23 (76.7%) patients with fibrohyaline repair, and 54 (74.0%) patients with fibrocartilage repair. By years 3 and 4 post-implantation, clinical scores further improved in patients with hyaline-like repair yet declined in those with fibrocartilage and fibrohyaline. The difference was significant at 3 years though not at 4 due to the small number of cases. Conclusions: Achieving hyaline-like repair is critical to the longevity of cartilage repair. The finding of hyaline-like cartilage or fibrohyaline cartilage in 31 of 37 biopsies (84%) performed after 2 years is therefore encouraging and supports further use of the ACI technique

Over the last 10 years ACI (Autologous Chondrocyte Implantation) has become an important surgical technique for treating large cartilage defects. The original method has been improved by using cell seeded scaffolds for implantation. The aim of our prospective study was to evaluate the efficiency of a matrix based ACI (MACI) with a collagen type I scaffold for repairing large cartilage defects of the knee. We present the clinical and radiological results of 22 pts. one year after collagen scaffold based ACI. Out of 39 pts. treated with ACI for cartilage defects of the knee 22 had reached the one year follow up. We documented preoperatively and postoperatively (3, 6 and 12 months) the clinical situation with the IKDC Knee Examination Form. MRI scans were evaluated at all time points. 41% of the pts. were female, 59% male. The average age was 33 yrs. (min:15; max:49), the average BMI 25,4 (min:19; max:36). One third of the cartilage defects were localized retropatellar, the remaining on the medial or lateral femoral condyle. The average defect size was 5.7 cm2. In about 75% of the cases an additional surgical procedure was performed (ACL-reconstruction, lateral release, meniscal surgery). One major complication (a deep wound infection) occured. The IKDC score improved over time during follow up significantly. Patients with retropatellar defects have a poorer outcome compared to femoral defects. The MRI showed an improvement of the implanted scaffold over time as well. The present study confirms the benefits of MACI in young patients with large cartilage defects of the knee. The matrix based ACI is a surgically less demanding technique then the traditional ACI. We expect a good long term outcome from MACI comparable to that of traditional ACI

Background. Autologous Chondrocyte Implantation (ACI) is a procedure which is gaining acceptance for the treatment of cartilage defects in the knee with good results and a long term durable outcome. Its use in other joints has been limited, mainly to the ankle. We aimed to assess the outcome of ACI in the treatment of chondral and osteochondral defects in the hip. Methods. Fifteen patients underwent ACI for chondral or osteochondral defects in the femoral head with a follow up of upto 8 years (mean of 2 years) in our institution with a mean age of 37 years at the time of operation. Pre-operatively hip function was assessed by using the Harris Hip Score and MRI. Post-operatively these were repeated at 1 year and hip scores repeated annually. Failure was defined as a second ACI to the operated lesion or a conversion to a hip resurfacing or replacement. Results. The mean pre-op Harris Hip Score (HHS) was 55 which increased to 63 at 1 year and 70 at the latest follow up. Patients who underwent ACI for cartilage defects secondary to trauma (four) were better with a mean HHS of 69 at a mean follow up of 3.5 years. Six patients underwent THR at a mean of 32 months and were classed as failures. Five patients had evidence of avascular necrosis (AVN) of the femoral head post operatively of which four AVN pre-op. Conclusion. These early results suggest that ACI could be a viable option for the treatment of isolated chondral defects in the hip. The presence of AVN or bone cysts pre-op may be a predictor of failure

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

Background. The meniscal deficient knee often exists in the setting of associated pathology including instability, malalignment and chondral injury. Meniscal allograft transplantation (MAT) is established to be a reliable option in restoring function and treating symptoms. The aim of this study was to establish the role of MAT as part of a staged approach to treatment of the previously menisectomised knee. Methods. This prospective study included all patients that underwent arthroscopic MAT at our institution between 2010 to 2017. Fresh frozen allograft was utilised using a soft tissue fixation technique. Further data was collected for index surgical procedures before and after MAT. Data for pre and post-operative Knee Injury and osteoarthritis outcome scores (KOOS), Tegner scores, graft survival, reoperation rates, patient satisfaction and MRI extrusion measurements were collected and details of any further surgical intervention and / or complications also documented. Results. Twenty seven MAT procedures were performed in 26 patients. Sixteen patients underwent lateral MAT and 11 patients medial. Ten patients underwent ACL reconstruction, three ACI and two, osteotomy in the pre-MAT phase. A further seven patients underwent ACI within the post-operative phase. The post-operative mean KOOS scores improved significantly in all subscales as did Tegner scores. Graft survival was 100%, satisfaction rate 92%, and mean meniscal extrusion 3.04mm. Post operatively, three patients required meniscal repair and a single patient partial menisectomy of graft. Two patients underwent arthroscopic arthrolysis following MAT. Conclusions. This series highlights the multifactorial profile of the meniscal deficient knee and the role of MAT as a safe and reliable technique in the staged and comprehensive biologic treatment available to minimise symptoms and maximise outcomes

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

Background. Autologous Chondrocyte Implantation (ACI) is frequently used to treat chondral defects in the knee with a good long-term outcome. This is contraindicatd in meniscal deficient knees. Allogenic Menicsal Transplantation (AMT) has been shown to give good symptomatic relief in meniscus deficient knees. However this is contraindicated in advanced cartilage degeneration. We hypothesized that combination of these two might be a solution for bone-on-bone arthritis in young individuals. Methods. We studied a consecutive series of 12 patients who underwent combined ACI and AMT between 1998 and 2005. Pre operative and post operative comparisons of lysholm scores were recorded. Magnetic Resonance Imaging was performed to assess the integration ACI & AMT. Arthroscopy was performed at one year for assessment and obtain biopsy for histological examination. Results. Out of the twelve patients only eleven were included as one had died at three months after surgery. The median pre-operative lysholm score was 45 which rose to 64 at one year. Magnetic Resonance Imaging showed good integration of both ACI and menisci. Most of the patients were able to lead an active lifestyle. Conclusion. The combination of both ACI & AMT could give a good result and defer a total knee replacement in young indi

Background & Aim: Recent studies have claimed good results after ACI in athletes. Our aim was to evaluate the early functional outcome and activity level after 2-stage ACI in professional athletes and soldiers. Methods: Thirteen soldiers and five professional athletes (14 men and 4 women; average age 31 years), with 21 full thickness cartilage defects (ICRS grade-IV) of the knee were treated with 2-stage ACI. Mean interval between injury and surgery was 43.8 months. Average defect size was 6.03 cm. 2. and was located to the MFC in 7 cases, LFC in 7 cases and the femoral trochlea in one case. The functional outcome was evaluated with ICRS form, Tegner activity rating scale and Lysholm score after a mean follow up period of 23.4 (18–32) months. Results: The ICRS and Lysholm scores were improved from 42.7 and 47.6 pre-operatively to 63.1 and 69.9 respectively. The average Tegner scale was 8.8 pre-injury, 3.7 prior to surgery and 6.4 at the final follow up. Nine patients (50%) underwent second-look arthroscopy for persistent mechanical symptoms. Periosteal flap overgrowth was identified in 6 cases with adequate graft integration while partial failure of the graft was noted in one case and was treated with microfracture. Conclusions: The early results of ACI in high-performance athletes and professional soldiers are not as good as other studies suggest. Returning to pre-injury performance levels for athletes and military people is by no means assured in the first 24 months after ACI

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?

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

Introduction: ACI is used widely as a treatment for symptomatic chondral and osteochondral defects of the knee. Variations of the original periosteum-cover technique include the use of porcine-derived type I/type III collagen as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) using a collagen bilayer seeded with chondrocytes. We report the minimum 2 year follow-up results of 192 patients randomised to autologous chondrocyte implantation (ACI) using porcine-derived collagen membrane as a cover (ACI-C) and matrix-induced autlogous chondrocyte implantation (MACI) for the treatment of osteochondral decfects of the knee. Methods: 192 patients (mean age 34.2) were randomised to have either ACI (86 patients) or MACI (106 patients). 1 year following surgery patients underwent check arthroscopy (with or without biopsy) to assess the graft. Functional assessment was performed yearly by using the modified Cincinatti knee score, the Bentley functional rating score and the visual analogue score. Results: 24 patients were excluded from the study as they underwent additional procedures (e.g. high tibial osteotomy). In the ACI group the modified Cincinatti score increased from 42.5 pre-operatively to 56.7, 54.1, and 60.4 at 1 year, 2 years and 3 years respectively. In the MACI group the Cincinatti scores increased from 46.0 pre-operatively to 59.9, 58.9, and 58.4. Arthroscopic assessment showed a good to excellent International Cartilage Repair Society score in 90.7% of ACI-C grafts and 68.4% of MACI grafts. Hyaline-like cartilage or hyaline-like with fibrocartilage was found in biopsies of 51.9% of ACI-C grafts and 25.9% of MACI grafts. Conclusions: ACI grafts are more likely to produce hyaline-like or mixed hyaline-like cartilage and fibro-cartilage with better ICRS grades than MACI grafts. However, this does not translate to better a clinical functional outcome. More importantly, ACI and MACI had similar results that were maintained at 3 years

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: Articular cartilage injuries are very common. Small defects don’t heal on their own and large defects can’t regenerate new cartilage. This would largely be due to the fact that chondrocytes are embedded in a firm and tough matrix and hence can’t migrate to the defect site to regenerate a new cartilage tissue. So ultimate fate is patient getting early osteoarthritis. Cartilage defects in the knee may be symptomatic and cause pain, swelling and catching. There are several different surgical procedures available to treat cartilage injuries, but no method has been judged superior. The ultimate aim of the treatment is restoration of normal knee function by regeneration of hyaline cartilage in the defect, and to achieve a complete integration to the surrounding cartilage and underlying bone. Arthroscopic debridement and lavage may give symptomatic relief for a limited time. Autologous Chondrocytes Implantation (ACI) was first described in 1994. Encouraging primary results were reported, and further research was promoted. Long-term results are encouraging. ACI is being done in Robert Jones & Agnes Hunt orthopaedic Hospital, Oswestry since last 8 years. Methods: We studied a cohort of first 118 patients who underwent ACI for knee joint in this institute, focussing on their mid-term results. Patients having chondral defects were offered ACI. They all were explained the procedure and informed written consent was obtained. Patients filled in a self-assessed Lysholm forms before the operation. They also underwent pre-operative MRI scan of knee joint. ACI procedure consisted of three stages— Stage I —Arthroscopic harvest biopsy of cartilage and chondrocytes culture in lab. Stage II—Arthrotomy of the knee. The defect edges were freshened, covered by periosteum or chondroguide, which was sutured to the cartilage with 6-0 vicryl. Chondrocytes were injected underneath this patch. Post-op CPM and Physiotherapy. Stage III—1-year arthroscopic surgery. Assessment was done with Lysholm score, MRI scan, histological and arthroscopic analysis. Patients were followed up clinically thereafter with yearly Lysholm scores. Results: 118 patients with an average age of 35 years (15–59) underwent ACI for knee in last 8 years. 93 patients had single defect, 24 had multiple (> 1) chondral defects, with mean area 4.81 cm2. MRI showed a good integration of defect with surrounding cartilage with varied signal intensities. About 55–56% patients underwent some or other form of trimming, which improved immediate results. However only 50 % of these were symptomatic. Defects on MFC did well as compared to other sites, followed by on trochlea. Defects on patella showed poor results, though the number is less for comparison. Total 79 specimens of 1-year histology showed good healing with formation of fibrocartilage (40), mixed (20) and hyaline (8), fibrous tissue (6), bone in 1 case and inconclusive in 2 cases. Mean pre-op Lysholm score was 50.16. Average score at one year was found to be 69.52. Conclusion: Results of ACI are encouraging. Patients continued to improve slowly over a period of time, achieving maximum function between one and 2 years post-surgery. Our study showed that there after their scores remained static

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 and purpose: Several factors (vascular, morphological, biomechanical, etc.) have been associated with the etiopathogeny of the rotator cuff. The purpose of this study is to assess the influence of the acromial coverage index (ACI) on the development of rotator cuff tears. Materials and methods: A comparative analysis was made of three groups of patients with a total of 62 females and 47 males with a mean age of 49.84 years. Group I included patients operated on for a rotator cuff tear (n=45), group II contained patients with a rotator cuff tear which evolved satisfactorily with rehabilitation treatment (n=36) and group III was made up of a group of control individuals with no pathology (n=38). All patients in groups I and II had a rotator cuff tear detected via either MRI or Arthro-CT. ACI is defined as the perpendicular to the tangent of the glenoid cavity until the outermost part of the acromion and the perpendicular to the tangent of the glenoid cavity which coincides with the diameter of the humeral head. Results: Group I had a mean ACI of .68, group II of .72 and group III of .59, i.e. there are statistically significant differences between groups I and III (p< 0.0001) and between group II and III (p< 0.0001). No statistically significant differences exist between group I and II (p< 0.219). No statistically significant differences exist between right and left arm involvement (p< 0.471). There are statistically significant differences between males and females (p< 0.0001). Conclusions: (1) ACI is significantly higher in patients with rotator cuff tears than in the control group. (2) ACI is significantly higher in females than in males. (3) There are no statistically significant differences with respect to the involvement’s laterality. (4) ACI would seem to have an influence on the etiopathogeny of rotator cuff tears

Introduction. We report the initial 2 and 3 year follow-up results of this randomised controlled trial of autologous chondrocyte implantation (ACI) using porcine-derived collagen membrane as a cover (ACI-C) versus matrix-carried autologous chondrocyte implantation (MACI) for the treatment of osteochondral defects of the knee. Methods. 217 patients were randomised to have either ACI (92 patients) or MACI (125 patients). The mean age in each group was 35.1 and 33 years respectively. There were equal proportion of males and females and there was no difference in the size of lesions in each of the treatment groups. One year following surgery, patients underwent check arthroscopy (with or without biopsy) to assess the graft. Functional assessment was performed yearly by using the Modified Cincinatti Knee score, the SF-36 score, the Bentley Functional Rating Score and the Visual Analogue Score. Results. 32 patients (27 from the MACI group) were excluded from the study as they underwent additional procedures (e.g. high tibial osteotomy). In the ACI group the modified Cincinnati score increased from 45.2 pre-operatively to 56.7, 54.1, and 65.4 at 1 year, 2 years and 3 years respectively. In the MACI group the Cincinnati scores increased from 45.5 pre-operatively to 59.9, 58.9, and 63.4. Arthroscopic assessment showed a good to excellent International Cartilage Repair Society score in 91.4% of ACI-C grafts and 76.1% of MACI grafts. Hyaline-like cartilage or hyaline-like with fibrocartilage was found in biopsies of 48.6% of ACI-C grafts and 30.5% of MACI grafts. Conclusions. ACI grafts are more likely to produce hyaline-like or mixed hyaline-like cartilage and fibrocartilage with better ICRS grades than MACI grafts. However, this does not translate to a better functional outcome. More importantly, ACI and MACI had similar results that were maintained at 3 years

Patients with osteochondral lesions of the talus have traditionally been difficult to treat. Autologous chondrocyte implantion (ACI) may provide predictable repair through restoring an articular surface. We reviewed our results of Ankle ACI in eight ACI plus two ACI and mosaicplasty combined with an average age of 40 years (32 to 62) performed over four years. The patients were assessed with a modified Mazur ankle score, patient satisfaction score and Lysholm knee score, pre- and post-operatively. Ankle arthroscopic assessment was performed in patients at 12 months post surgery. The average time to follow up was 24 months (range two to 52). The osteochondral lesions were post traumatic in seven cases, with seven lesions situated medially and three anterolaterally. The average size of the talar defects at surgery was 2.25cm (range 1 to 4 cm.). Patient satisfaction scores in eight patients were either “extremely pleased” or “pleased” with the operation which was sustained in the patients at up to four years follow up. The Mazur scores increased by 23 points at mean 24 months follow up. Six patients with over 12 months follow up maintained a markedly improved ankle score. Patients were noted to rehabilitate twice as quickly as patients receiving ACI to the knee. The Lysholm knee scores returned to the preoperative level in four patients, with the remaining six patients showing a reduced score (mean 12 points), suggesting there may be some donor site morbidity. Five had ankle arthroscopy at one year and were shown to have filled defects and stable cartilage. A biopsy taken from the graft site showed hyaline like cartilage and fibrocartilage to be present These early results suggest that ankle ACI is an appropriate treatment for large symptomatic osteochondral lesions in the talus

Mosaicplasty. 1. and Autologous Chondrocyte Implantation. 2. (ACI) are both modern cartilage repair techniques used to repair symptomatic articular cartilage defects in the knee, based on small osteochondral grafts and cultured chondrocytes respectively. The aim is the restoration of articular cartilage, but until now there is no data comparing the two methods. 100 consecutive patients aged 15–45 with a symptomatic articular cartilage lesion in the knee suitable for cartilage repair were randomised at arthroscopic assessment to undergo either mosaicplasty or ACI. 42 patients underwent mosaicplasty, 58 had ACI. Mean age at time of surgery was 31 years and the average defect size 4. 66 cm. 2. . 46% of the defects were post-traumatic, 19% had osteochondritis dissecans, 14% had chondromalacia patella and 16% had lesions of unknown aetiology. 53% had a medial femoral condyle lesion, 25% patella, 18% lateral femoral condyle, 3% trochlea and there was one defect of the lateral tibial plateau. The mean duration of symptoms was 7. 2 years and the average number of previous operations (excluding arthroscopies) was 1. 5. Only 6 patients had no prior surgical interventions to the affected knee. The mean follow-up was 1. 7 years. Patients were evaluated using Modified Cincinnati and Stanmore Functional rating systems, visual analogue scores and clinical assessment. Arthroscopy and biopsy was performed at one year and repair assessed with the International Cartilage Repair Society grading system. Clinical results at one year showed 70% of mosaic-plasty patients and 87% of ACI patients had a good or excellent result. Arthroscopy at one year demonstrated more complete healing in ACI patients. Eleven (26%) of the mosaicplasty group subsequently failed clinically and arthroscopically, with peak failure at 2 years. At one year follow-up, both techniques of articular cartilage repair can be useful in selected patients. ACI is preferred for lesions of the patella. Long-term follow-up is needed to assess the durability of articular cartilage repair using these methods, in particular mosaicplasty which showed signs of progressive failure over 2 years

Traditionally, the results of autologous chondrocyte implantation (ACI) in the patellofemoral joint have been considered inferior to those in the weightbearing femoral condyles. This study investigated the clinical effectiveness of patellofemoral ACI in a large, single-surgeon cohort. This study reviewed prospectively collected data of patients treated with ACI for defects of the trochlea and/ or patella with a minimum follow-up of 2 years. Clinical outcomes were evaluated by SF-36; WOMAC, Knee Society Score, modified Cincinnati Score and a patient satisfaction survey. 130 patients reached a minimum follow-up of 2 years (2–9 years, average 56.5 months) after treatment involving the patellofemoral articulation. There were 77 men (59%) and 53 women (41%), the average age at the time of implantation was 37.5 years (15–57 years). The treatment groups included. isolated patella (n = 14);. isolated trochlea (n = 15);. patella plus trochlea (n = 5);. weight-bearing condyle plus patella (n = 19);. weightbearing condyle plus trochlea (n = 52);. weightbearing condyle plus patella plus trochlea (n = 25). The average surface area of patellar and trochlear defects was 4.7 cm2 (n = 63) and 5.8 cm2 (n = 98), respectively. The average resurfacing per knee was 11 cm2. There were 16 failures (12%) that could be attributed to a patellar or trochlear defect. 80% of patients rated their outcome as good or excellent, 18% rated their outcome as fair, and 2% rated outcome as poor. ACI of the patellofemoral articulation provided a Significant improvement in quality of life as measured by functional scores and patient satisfaction survey. The failure rate was comparable to ACI used in other locations, such as the weightbearing femoral condyles

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

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

The current study aims to ascertain the outcome of ACI with simultaneous transplantation of an autologous bone plug for the restoration of osteoarticular defects in the femoral condyle of the knee (‘Osplug’ technique). Seventeen patients (mean age of 27±7 years), twelve with Osteochondritis dissecans (OD) and five with an osteochondral defect (OCD) was treated with unicortical autologous bone graft combined with ACI (‘Osplug’ technique). Functional outcome was assessed with Lysholm scores obtained for 5 years post-operatively. The repair site was evaluated with the Oswestry Arthroscopy Score (OAS), MOCART MRI score and ICRS II histology score. The mean defect size was 4.5±2.6 SD cm² and mean depth was 11.3±5 SD mm. A significant improvement of Lysholm score 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 MRI and low OAS were significantly associated with a poor outcome and failure. The Osplug technique shows significant improvement of functional outcome for up to 5 years. This is the first report describing the association of bone graft integration with functional outcome after such a procedure

Introduction and Aims: The treatment of cartilage defects has been revolutionised by the introduction of autologous chondrocyte implantation (ACI) over the last decade. Several studies have shown superior clinical and histological results compared to traditional treatments such as mosaicplasty. ACI involves injecting chondrocytes into the defect and sealing it with periosteum or chondroguide membrane. Recently, a new technique has been introduced which allows chondrocytes to be embedded within a matrix which is then used to fill the cartilage defect. The aim is to assess the early functional, clinical and histological results of MACI for the treatment of full-thickness cartilage defects. Method: This is a prospective study. Fifty patients, mean age 34 (range 19–62) underwent MACI for their cartilage repair. The modified Cincinnati, Brittberg and Lysholm and Gillquist scores were used to assess functional outcome. These were compared with the results obtained in 40 patients; mean age 31 (range 15–51) treated with ACI. A review of the histology in both groups was carried out. Results: At two-year follow-up, functional assessment using the Brittberg and modified cincinnati scoring systems, as well as objective clinical assessment, showed that more than 75% of patients had good or excellent results following treatment with either ACI or MACI. There was no statistical difference in the functional scores between the two groups (p < 0.05). Histological results were similar in both groups. Conclusion: Our prospective study has shown that results of MACI are comparable to that obtained by ACI. Additional advantages of the MACI technique being a shorter operative time, easier technique and potential to treat larger defects

Purpose: To define the role of ACI in treatment of cartilage defects in the knee joint. Method: 106 articular cartilage defects in 79 knees of 77 patients were treated by ACI as described by Brittberg et al, 1994. 43.5% of the lesions involved the patella, 35.2% the femoral condyles, 16.7% the trochlea, and 4.6% the tibial condyles. 20% of knees had more than one defect. Associated biomechanical procedures were carried out in 88.7%. Results: 70 lesions in 58 knees and 56 patients were assessed arthroscopically 9 months after implantation; 4 eligible patients were not assessed. The average ICRS repair score (maximum 12) was as follows: tibial condyle 11.5, (4 defects); patella 11.3, (32 defects); femoral condyle 11.0, (23 defects) and trochlea 10.7, (11 defects). Synovitis was markedly reduced in all knees with well healed defects. Contraindications to ACI in this series were:. Non-contained defects,. Bi-polar lesions,. Patients greater than 45 years,. Uncorrected biomechanics,. Regional pain syndrome type 1,. Limited joint movement,. Defective subchondral bone plate. Conclusion: ACI effectively repairs articular cartilage defects in the knee joint, provided that the contraindications are recognised. Unlike other series, the results for the patella, patellofemoral joint have matched those for the femoral condyle. This is attributed to the simultaneous biomechanical correction of the patellofemoral joint. Stabilisation of the articular surface results in resolution of synovitis

Joint surface restoration of deep osteochondral defects represents a significant unmet clinical need. Moreover, untreated lesions lead to a high rate of osteoarthritis. The current strategies to repair deep osteochondral defects such as osteochondral grafting or sandwich strategies combining bone autografts with ACI/MACI fail to generate long-lasting osteochondral interfaces. Herein, we investigated the capacity of juvenile Osteochondral Grafts (OCGs) to repair osteochondral defects in skeletally mature animals. With this regenerative model in view, we set up a new biological, bilayered, and scaffold-free Tissue Engineered (TE) construct for the repair of the osteochondral unit of the knee. Skeletally immature (5 weeks old) and mature (11 weeks old) Lewis rats were used. Cylindrical OCGs were excised from the intercondylar groove of the knee of skeletally immature rats and transplanted into osteochondral defects created in skeletally mature rats. To create bilayered TE constructs, micromasses of human periosteum-derived progenitor cells (hPDCs) and human articular chondrocytes (hACs) were produced in vitro using chemically defined medium formulations. These constructs were subsequently implanted orthotopically in vivo in nude rats. At 4 and 16 weeks after surgery, the knees were collected and processed for subsequent 3D imaging analysis and histological evaluation. Micro-computed tomography (µCT), H&E and Safranin O staining were used to evaluate the degree of tissue repair. Our results showed that the osteochondral unit of the knee in 5 weeks old rats exhibit an immature phenotype, displaying active subchondral bone formation through endochondral ossification, the absence of a tidemark, and articular chondrocytes oriented parallel to the articular surface. When transplanted into skeletally mature animals, the immature OCGs resumed their maturation process, i.e., formed new subchondral bone, partially established the tidemark, and maintained their Safranin O-positive hyaline cartilage at 16 weeks after transplantation. The bilayered TE constructs (hPDCs + hACs) could partially recapitulate the cascade of events as seen with the immature OCGs, i.e., the regeneration of the subchondral bone and the formation of the typical joint surface architecture, ranging from non-mineralized hyaline cartilage in the superficial layers to a progressively mineralized matrix at the interface with a new subchondral bone plate. Cell-based TE constructs displaying a hierarchically organized structure comprising of different tissue forming units seem an attractive new strategy to treat osteochondral defects of the knee

Introduction. Meniscus deficiency leads to the development of early arthritis. Total knee replacement may be the only available treatment option in certain situations. However it is generally best avoided in young patients. We hypothesized that a combination of the two procedures, Allograft Meniscal Transplantation (AMT) and Autologous Chondrocyte Implantation (ACI) would be a solution to treat bone-on-bone arthritis in meniscal deficient knees and postpone the need for a total knee replacement (TKR). Materials/Methods. 12 consecutive patients who underwent both ACI and AMT between 1998 and 2005 were followed up prospectively. The patients were assessed by a self-assessed Lysholm score prior to the procedure and yearly thereafter. All operations were performed by the senior author (JBR). ACI procedure was performed according to the standard technique. Frozen meniscal allograft with bone plugs at either ends secured by sutures in the bone tunnels. Post operatively all patients underwent a strict Oscell Rehabilitation protocol. A repeat procedure or progression to a TKR was taken as a failure. Results. Out of the twelve patients only eleven were included as one had died at three months after surgery. Three patients had delayed TKR, and two were heading towards TKR at 8 years. The median pre-operative lysholm score in the remaining six patients rose from 45 to 64 at last follow up. Conclusions. In our small pilot study there was a 19 point increase in the lysholm score. The combination of ACI & AMT could give a good result defer the need for TKR

Aim: To report the clinical and histological outcome of autologous chondrocyte implantation (ACI) using two techniques -collagen covered ACI or ACI-C and matrix carried ACI or MACI- over eight year period. Patients and methods: One hundred and seventy one patients (61 ACI-C and 110 MACI) who underwent ACI were followed-up prospectively using both objective and patient reported clinical outcome measures. Biopsy of the repair tissue was performed in 115 patients. The mean clinical follow-up was 39.4 months (13mths to 8 years) and the mean timing of biopsy was 14.8 months. The mean age at the time of surgery was 32 years (15 to 55 years). The site of defect was as follows: medial femoral condyle-95, lateral femoral condyle-25, trochlea-7, patella 27 and multiple sites- 12. The mean proportion of viable cells available for implantation was 96.3 % (range: 86 to 100) and the mean number of multiplication of cells during culture was 90 (range: 9 to 667). Results: 79 % of patients had an improvement in clinical outcome, 5 % of patients had no difference and 16 % had deterioration in clinical outcome. Short Form 36 (SF-36) health survey assessments demonstrated significant improvements in both mental and physical component scores (p< 0.001). The number of patients who demonstrated hyaline-like, mixture of hyaline-like and fibrocartilage, fibrocartilagenous and fibrous tissue histology were 32, 22, 59 and 2 respectively. The most favourable sites were lateral femoral condyle and trochlea where as the least favourable site was patella. There was no correlation between the mental score of patients and the final clinical result. Improvement in functional score was significantly higher among those who had a higher pre-operative function (p< 0.001). There were 7 patients who had previously failed micro-fracture and all of them obtained significant improvements in pain and function. Those who had a higher proportion of viable cells after cell culture demonstrated a tendency towards better outcome, but failed to reach statistical significance (p=0.14). There was no correlation between the number of cell multiplications at the time of cell culture and final clinical outcome (p=0.65). There was no significant difference in clinical outcome between the ACI- C and MACI techniques of ACI (p> 0.05). Conclusion: Autologous chondrocyte implantation is a useful procedure for patients with symptomatic chondral defects of the knee and produces significant improvement in both objective and patient reported clinical outcome scores in up to 79 % of patients

Introduction: Before proceeding to long-term studies, we studied early clinical results of combined Autologous Chondrocyte Implantation (ACI) and Allogenic Meniscus Transplantation (AMT). Meniscus deficient knees develop early osteo-arthritis (OA) of the knee joint. Autologous Cartilage Implantation (ACI) is contraindicated in case of meniscus deficient knees. And on contrary the Allogenic Meniscus Transplantation (AMT) is contraindicated in cartilage defects in the knee joint. But a combination of the two procedures for bone on bone OA might be a solution for this problem. This was the main purpose of our study. Methods: We studied a consecutive series of eight patients (7 males and 1 female), with an average age= 43 years (29–58), presenting with painful secondary arthritis, due to premature loss of meniscus and chondral defect/s. Median size of the femoral defects was 8.16 cm2 and of the tibial side 2.69 cm2 All patients were treated with a combination of Autologous Chondrocyte implantation (ACI) and Allogenic Meniscus Transplantation (AMT). Chondral defects were covered with periosteum/ Chondroguide membrane, secured in place with in-vitro cultured autologous chondrocytes injected underneath the path. Meniscus placed as load-bearing washer on the surface of ACI of tibia. ACI rehabilitation protocol followed post-operatively. Assessment at the end of one year was done with self-assessed Lysholm score, histology and the MRI scan. Results: Mean pre-operaive Lysholm score was 49 (17–75). This increased to a mean of 66 (26–87) at 1 year, an average increase of 16.4 points. Average one-year satisfaction score was 3 and they were back to all active life style. Five out of eight patients showed significant functional improvement at last post-operative follow-up (2 to 6 years; mean of 3.2 years). Complications were aseptic synovitis in 3 cases. Three failures were noted showig persistant pain and swelling in one, rupture of meniscus in second and third patient had a knee replacement. Arthroscopy at 1 year showed a stable meniscus with all healed peripheral margins in all except in one case with some thinning with no evidence of rejection. Histology of meniscus showed a fibrocartilage well populated with viable cells and the peripheral zone was well vascularised and integrated with capsule. Biopsy of ACI site was predominantly of fibrocartilage with good basal integration with subchondral bone. On MRI scan, allogenic meniscus was well integrated with capsule along the line of repair, showing foci of variable signal intensities within the meniscus. There was no evidence of meniscal subluxation in all but one case showing mild extrusion. ACI graft site showed a varied appearance, with 3 grafts showing focal grade 3to 4 changes. Conclusion: Seven out of eight patients improved post-operatively at one year, in terms of pain relief and increased activity. It’s possible to combine these two techniques together. Short-term outcomes are satisfactory. We could not find any deleterious effects of combining these two techniques together. So we conclude that, this might act as a one step towards a biological knee replacement

Introduction: Autologous Chondrocyte Implantation (ACI) is a treatment option for symptomatic, full-thickness chondral/osteochondral injuries. Goals of surgery and rehabilitation include replacement of damaged cartilage with hyaline/hyaline-like cartilage, leading eventually to improved level of function. Intermediate and long-term results are promising in terms of functional improvement. Purpose: To explore the hypothesis that non-hyaline cartilage repair tissue is associated with worse functional outcome and to assess whether the quality of the repair tissue formed following ACI improves with time post-surgery. Methods and Results: Two hundred and forty eight patients who underwent ACI at our institution were studied, having had post-implantation biopsies of the repair tissue. Mean timing of biopsy was 14.8 months (range 3–55). 59 biopsies showed hyaline tissue (24%), 67 mixed hyaline and fibrocartilage (27%), 113 biopsies were fibrocartilage only (46%) and 9 patients had a fibrous tissue biopsy result (9%). 126 patients (51%) had hyaline tissue in the regenerate and demonstrated a mean Modified Cincinnati Rating Score (MCRS) of 84 and a mean Lysholm Score of 88 at last follow-up (Group 1). 122 patients (49%) had no hyaline tissue in the regenerate and scored a mean MCRS of 71 and a mean Lysholm Score of 73 (Group 2). Both Groups 1 and 2 demonstrated a statistically significant improvement in functional outcome between pre and post-operative scores (p< 0.0001). There was significant difference in post-operative scores between Groups 1 and 2 suggesting that presence of hyaline tissue in the regenerate is associated with improved functional outcome (p< 0.05). Finally, our statistical analysis suggested that if time post-implantation doubles, then the likelihood of a favourable histological outcome increases significantly. Conclusion: ACI forms a durable repair tissue that remodels and continues to improve in quality with time. Poor functional outcome may reflect the presence of a non-hyaline cartilage repair tissue

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

Introduction: 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. There is only one published report of its use in the hip. Is there a role for ACI of the hip?. Materials and Methods: We describe fourteen consecutive patients studied prospectively with chondral or osteochondral lesions of the femoral head that underwent ACI and were prospectively reviewed with a follow up of 5 years (mean 30 months). Three patients presented with Perthes and five with AVN. Four had chondral loss following trauma and one presented with an area of bone loss in a hip with congenital dysplasia. Defect size was a mean 6.2 cm2. Pre-operatively hip function was assessed by the patient using the Harris Hip Score and MRI. Postoperatively these were repeated at 1 year and hip scores repeated annually. Hip arthroscopy and cartilage biopsy provided Cells for culture in a GMP laboratory where passage numbers were limited to two. Three weeks later by open surgery, all unstable cartilage was excised, the base was debrided or excised and bone graft applied, and suture of a membrane of periosteum or collagen membrane over the defect undertaken. A mean 5.2 million chon-drocytes were inserted beneath this patch following a test of the seal. Results: Ten of the fourteen patients improved at one year, with a mean rise in Harris Hip score from 57 to 63 points. Five patients underwent arthroscopic examination at one year and in four there was evidence of good integration of the new cartilage. In one patient arthros-copy was difficult due to previous trauma. One patient developed AVN as a post-operative complication following a posterior approach. Four patients have progressed to hip replacement or resurfacing but it is of note that all these patients had cyst formation pre-operatively. Conclusion: The short-term results of ACI for osteo-chondral lesions of the hip suggest that if good early results are obtained they are observed to continue out to 5 years. There is a high failure rate in those with pre-operative cyst formation in the hip

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

Introduction and Aims: Autologous chondrocyte implantation (ACI) is emerging as a leading technique for the treatment of articular cartilage defects. However, there exists some debate regarding which ACI technique is best able to regenerate hyaline cartilage. To this end, the development of a non-invasive technique enabling the examination of microstructure after ACI is essential. Method: In this study, we have developed a novel 2D Laser Scanning Confocal Arthroscope (LSCA) in the assessment of articular cartilage and examined the microstructure of knee articular cartilage from rabbits and patients with total knee arthroplasty. The LSCA system consists of the LSA handheld probe, a Launch and Detection Unit (LDU) with a built in 488nm–514nm Krypton Argon Laser and Master Control unit (MCU). Human and rabbit knee articular cartilage stained with Fluoroscein (5g/L) and Acriflavine (0.5g/L) were used to examine the microstructure of cartilage by LSCA. Results: By LSCA we have generated optical histology images of normal human and rabbit articular cartilage from the femoral condyle. Optical histology of normal articular cartilage tissue reveals typically smooth surface texture with relatively homogenous sub-surface distribution of viable chondrocyte cells. The general orientation of collagen fibres is occasionally visible in surface images. Optical histology of arthritic cartilage of humans showed clusters of round-shaped chondrocytes mixed with spindle-shaped cells. Surface cracking typically indicative of tissue damage is also evident by LSCA observation. Examination of rabbit knee six weeks after ACI showed high density of chondrocytes and homogeneous matrix on the site of the defect. Conclusion: In short, we have shown the efficacy of LSCA in the non-destructive assessment of articular cartilage in vivo. Further study is required to evaluate the clinical significance of optical histology of LSCA

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

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

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.

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.

To assess the clinical outcomes of patients undergoing ACI in the patellofemoral joint. Level of evidence. Therapeutic study, Level II-1 (prospective cohort study). In a prospective study to determine the clinical effectiveness of autologous chondrocyte implantation 130 patients reached a minimum follow up of two years (range, 2–9 years, average 56.5 months) after treatment involving the patellofemoral articulation. There were 77 men (59%) and 53 women (41%) with an average age of 37.5 years (range, 15-57years). The treatment groups included I) isolated patella, n = 14; II) isolated trochlea, n = 15; III) patella plus trochlea, n = 5; IV) weight bearing condyle plus patella n = 19; V) weight bearing condyle plus trochlea, n = 52; VI) weight bearing condyle plus patella plus trochlea n = 25. The average surface area per patella, n = 63, was 4.72 cm2 and per trochlea, n = 98, was 5.8cm2. The average resurfacing per knee, n = 130, was 11.03cm2. This prospective outcome study demonstrated a significant postoperative improvement in quality of life as measured by the SF-36; WOMAC, Knee Society Score, modified Cincinnati Score and a patient satisfaction survey. There were 16 failures (12%) as a result of a patella or trochlea failure. Eighty percent of patients rated their outcomes as good or excellent, 18% rated outcome as fair, and 2% rated outcome as poor. ACI is effective in the patellofemoral joint and specifically is a complementary intervention for those patients that will predictably do poorly with an isolated Fulkerson Tibial Tubercle osteotomy

Purpose: We attempted to identify whether patients with early evidence of osteoarthritis (OA) on their pre-operative radiographs were associated with poorer outcomes after Autologous Chondrocyte Implantation (ACI). Methods: We retrospectively reviewed radiographs of 94 consecutive patients who underwent ACI and had already had their knee function assessed according to the Modified Cincinatti Score 2 years following surgery. Changes were graded according to The Kellgren and Lawrence (K& L) and the Stanmore grading system. Two independent observers analysed the films to assess the reproducibility and accuracy of these grading systems for assessment of OA in the knee. Results: Patients were divided into 2 groups; Group A were patients with excellent/good outcome (52 patients), those with fair/poor outcome were Group B (42 patients).13 patients in Group A and 21 patients in Group B had radiographic evidence of OA (p< 0.025). In 34 patients who had OA (mean age 33.6) the increase in Cincinatti score following surgery was minimal (33.5 to 37.5). In 60 patients where there was no evidence of OA (mean age 33.7) the score increased from 40 to 53.4. The inter-observer variation was greater using K& L (Kappa=0.31) compared with the Stanmore grading systems (Kappa=0.72). Conclusions: Patients with early radiographic evidence of OA are unlikely to gain maximum benefit from ACI. Furthermore, we recommend the use of Stanmore grading system for the assessment of OA as it is more reproducible than the K& L grading system

Autologous chondrocyte implantation (ACI) has been used for many years for the treatment of symptomatic defects in articular joints, predominantly the knee. Traditionally, cells were implanted behind a periosteal membrane, but in more recent times Chondrogide, a membrane consisting of porcine collagens I and III, has been used. There have been trials comparing the clinical outcome of these two groups of patients; in this study we compare the histological outcome using the two different patch types. In a study of 100 patients having received ACI treatment of cartilage defects in the knee, 41 received Chondrogide (ACI-C) and 59 received periosteum (ACI-P). All of these patients had a post-operative biopsy taken at a mean of 16.9±9.2 months and 20.8±23.2 months for ACI-C and ACI-P respectively for histology using the ICRS II scoring system. Lysholm scores, a measure of knee function, were obtained pre- and post-operatively at the time of biopsy and statistical differences tested for via a Mann-Whitney U-test. The mean age of the two groups at treatment was 37±8 and 35±10 years, the size of defect treated was 6.1±5.4 and 4.4±2.7 cm2 and the biopsy follow-up time was 50.6±22.2 and 81.2±34.8 months for ACI-C and ACI-P patients respectively. Both groups exhibited a significant improvement in Lysholm score from pre-operative to the time of biopsy (14.3±25.7; n=100), although there was no significant difference in improvement in Lysholm score between the two patch types. There was no significant difference between the histology score of the two groups, nor was the score found to correlate with the Lysholm score at that time. The individual components of the ICRS II score did not differ significantly with patch type (even for the surface architecture) apart from cellular morphology which was 6.5±3 and 8.2±1.6 for ACI-C and ACI-P respectively. The histological quality of repair tissue formed with ACI-C differed little from that seen with ACI-P, despite the former group being biopsied ∼4 months sooner after treatment and being used to treat defects which were 39% larger. Hence Chondrogide appears just as suitable as periosteum for use as a patch in the procedure of ACI

High tibial osteotomy (HTO) is a recognised method of correction for knee joint malalignment and unicompartmental osteoarthritis. The long term results of this technique have been reported and are favourable. Autologous chondrocyte implantation (ACI-C, MACI) has also been reported to have good results It is advised that malalignment, if present, should be corrected if ACI is to be performed. Although results have been reported for either procedure separately, the outcomes of combined HTO-ACI remain unreported. To evaluate functional outcome in a group of patients undergoing combined HTO-ACI procedures. Twenty three patients undergoing a combined ACI-HTO procedure were identified retrospectively from a larger trial of patients undergoing ACI for symptomatic chondral defects. The mean follow-up was 54 months (range 12 – 108) and the mean defect size was 689 mm2 (range 350 – 1200). Nine patients had ACI-C and HTO, the remainder having MACI and HTO. Pre and postoperative assessment was carried out using the Visual Analogue Score (VAS), the Bentley Functional Rating Score and the Modified Cincinnati Rating System. The Mean VAS score improved from 7.4 pre-operatively to 2.9 post-operatively (p< 0.0001). The Bentley Functional Rating Score improved from 2.9 to 1.8 (p< 0.0001) whilst the Modified Cincinnati Rating System improved from 35.2 pre-operatively to 68.7 post-operatively (p< 0.0001). There was no significant difference between ACI-C and MACI. Two patients developed a non union at a mean of 13 months and a further two patients had a failure of the chondrocyte graft at a mean of 22.5 months. Combining high tibial osteotomy with autologous chondrocyte implantation is an effective method of decreasing pain and increasing function at mean of 54 months follow-up. Further follow-up is required to assess the long term outcomes of these combined procedures

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

High Tibial Osteotomy (HTO) is a recognised method of correction for knee joint malalignment and unicom-partmental osteoarthritis. Long-term results of this technique have been reported and are favourable. Good results have also been reported with Autologous Chondrocyte Implantation (ACI-C, MACI). Malalignment, if present, should be corrected when ACI is performed. Although results have been reported for either procedure separately, the outcomes of combined HTO-ACI remain unreported. The aim of this study was to evaluate functional outcome in patients undergoing combined HTO-ACI procedures. Twenty three patients undergoing a combined ACI-HTO procedure were identified retrospectively from a larger trial of patients undergoing ACI for symptomatic chondral defects. The mean age of the patients was 36 (28 – 49). The mean follow-up was 54 months (12 – 108) and mean defect size was 689mm2 (range 350 – 1200). Nine patients had ACI-C and HTO, the remainder having MACI and HTO. Pre and post-operative assessment was carried out using the Visual Analogue Score (VAS), the Bentley Functional Rating Score and the Modified Cincinnati Rating System. The Mean VAS score improved from 7.4 (4 – 10) pre-operatively to 2.9 (0 – 6) post-operatively at the latest follow-up (p< 0.0001). The Bentley Functional Rating Score improved from 2.9 (2 – 4) to 1.8 (0 – 4), which was statistically significant (p< 0.0001). The Modified Cincinnati Rating System improved from 35.2 (20 – 49) pre-operatively to 68.7 (46 – 85) post-operatively (p< 0.0001). Fourteen patients underwent biopsy of the graft site at a mean of 13.7 months: 21% of biopsies were hyaline-like cartilage, 36% were mixed hyaline/fibrocartilage, 29 % were fibrocartilage and 14% were fibrous tissue. Combining high tibial osteotomy with autologous chondrocyte implantation is an effective method of decreasing pain and increasing function in the short term. Further evaluation of this procedure is required

Background: In regenerative medicine the autologous cartilage implantation (ACI) has been used for the repair of cartilage defects. As modification of ACI, the matrix assisted ACI is used nowadays with varying results. There is a general discussion about whether supporting scaffolds should be used or whether a scaffold-free cartilage repair is the method of choice. The major problem of scaffold-free regenerates is how to keep the cells in place after transplantation. Aim of this study was to examine a new scaffold-free diffusion-culture model, which uses a mega-congregate of chondrocytes cultured at an air-medium interface. This scaffold-free high-density diffusion culture could be used to repair cartilage defects. Material and methods: Human chondrocytes from passage 1–7 were expanded in monolayer and transferred to pellet-culture or diffusion-culture. After one week cultures were stained with toluidine blue and safranin-O and evaluated by immunohistochemical staining for type II collagen. Quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) was performed for the mRNAs of cartilage markers. Results: Positive alcian blue staining was detectable in diffusion-culture for human chondrocytes up to passage 7. Within passages the amount of proteoglycan production in relationship to the number of cells increased. There was a positive signal for Collagen type II in diffusion-cultures up to passage 7. In qRT-PCR a redifferentiation of human chondrocytes was shown by the transfer into diffusion-culture. Within passage 1 to 3 human chondrocytes which were cultured in monolayer lost the ability to express Collagen Type II but could regain it if they were transferred to diffusion-culture. At diffusion-culture chondrocytes showed the highest expression of Collagen type II at passage 1 when compared to monolayer or to pellet-culture. Conclusion: It could be shown that the cultivation in a scaffold-free diffusion-culture can lead to redifferentiation of human chondrocytes Chondrocytes in diffusion-cultures tend to form their own matrix and produce Collagen type II at higher amounts than in monolayer or in normal pellet-cultures. Therefore diffusion-culture congregates might be an appropriate tool to be used for a new scaffold-free cartilage regeneration approach

Autologous Chondrocyte Implantation (ACI) is a technique for repair of isolated symptomatic articular cartilage defects in the young adult knee. The knee is arthroscopically assessed and a sample of cartilage is harvested from the margin of the joint, this is digested and the liberated chondrocytes expanded in culture. At subsequent arthrotomy, the articular cartilage lesion is debrided and the cells injected behind a sutured flap. A concern regarding ACI is the iatrogenic insult to non-injured healthy cartilage adjacent to that harvested for culture. Damaged cartilage around the lesion is routinely debrided and discarded at the second stage operation. The purpose of this study was to determine whether this damaged debrided cartilage could yield an adequate number of equivalent chondrocytes for ACL. Cells from 11 patients were analysed. The debrided “waste” from around the lesion was collected, enzymatically digested and the liberated chondrocytes cultured in monolayer. The cells were recovered and placed in a 3D-pellet culture in a defined medium. Chondrocytes obtained from the routine harvest of healthy cartilage were placed in a similar culture system. The two groups were compared using DNA and GAG assays, histological and immunohistochemical techniques. Chondrocytes obtained from the debrided cartilage lesion were equivalent to those obtained from the harvested healthy cartilage. Sufficient cell numbers for implantation were achieved for all patients, however cells cultured from the debrided defect in patients who had a large degenerate lesion required significantly longer in culture to attain the required number of cells. For many patients undergoing ACI, the potential iatrogenic insult to the joint cartilage of the harvesting procedure could be avoided by harvesting the damaged tissue from around the defect itself

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.

Aim: To evaluate the repair of articular cartilage defects in the knee treated by autologous chondrocyte implantation (ACI), using arthroscopic assessment. Method: One hundred and six articular cartilage defects in 79 knees of 77 patients were treated by ACI. The chondrocytes were injected beneath a periosteal flap (Brittberg et al, 1994). Arthroscopy and removal of the metal implants were performed nine months following implantation. The ICRS score was used to assess the repairs. Results: Of the 79 knees 43.5% of the lesions involved the patella, 35.2% the femoral condyles, 16.7% the trochlea, and 4.6% the tibial condyles. The average defect size was 254.65mm. 2. It was found that 20% of knees had more than one defect. Associated biomechanical procedures were carried out in 88.7%. Seventy lesions in 58 knees (56 patients) have been assessed; four eligible patients were not assessed arthroscopically. The ICRS scores (maximum 12) were: tibial condyle 11.5; patella 11.3; femoral condyle 11.0, and trochlea 10.7. Synovitis was markedly reduced in all knees with well-healed defects. Adhesions between the periosteal graft and the synovium caused a click in 11 patients, which was relieved by arthroscopic resection. Incomplete healing occurred in one patient with a wound dehiscence, in two following a fall in the post-operative period, and in one patient with a non-contained defect. Biopsies at arthroscopy showed predominantly hyaline cartilage. Conclusions: We concluded that ACI was an effective method of repairing articular cartilage defects. In this series the results for the patella matched those for the femoral condyle, attributed to the simultaneous biomechanical correction of patellofemoral dysplasia. Stabilisation of the articular surface resulted in resolution of synovitis

Chondral injury has become one of the most difficult problems to solve in orthopaedics. This pathology is very common: Curl et al. founded an incidence of 63% of chondral lesions (2.7 lesions for knee in 31,156 knee arthroscopies) with a 20% rate of lesions of grade IV of Outerbridge. During the past few decades many techniques were developed: with these techniques the lesion is just reparied with the formation of fibro-cartilage tissue with biochemical and bioelastic characteristics very different from the hyaline cartilage tissue. Microfracture technique : This technique, proposed by Steadman et al., utilises hand-drills to create numerous perforations in the subchondral bone at 3–4 mm apart. Indications for this techniques are lesions from 0.5 to 2 cm. 2. with an outlined border in patients with low functional demand. Osteochondral autograft transplantation (OATS, mosaicplasty): Osteochondral autograft transplantation is indicated for isolated lesions from 1 to 3 cm. 2. or in OCD. Outerbridge et al., in a study of 10 patients with 6.5 years of follow-up, achieved good functional results in all pateints treated with this technique. Autologous chondrocyte implant: ACI, reported for the first time by Peterson and colleagues 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 cm. 2. They. reported good results in the treatment of chondral lesion with a long follow-up (2–10 years). New tissue engeneering techniques with the use of biomaterial derived from hyaluronic acid provides ideal support to the culture and proliferation of chondrocytes, allowing at the same time arthroscopic implant. Today there are many options in the treatment of chondral lesions, but no one technique can be considered the gold standard. ACI in arthroscopy is a more promising technique in the treatment of the chondral lesions, but the indications are still too restricted

Introduction: Autologous chondrocyte implantation (ACI) is a technique described for treating symptomatic osteochondral defects in the knee. It is contra-indicated, however, in a joint rendered unstable by a ruptured anterior cruciate ligament (ACL). We present our early experience of combined ACL and ACI repair. Methods: Patients underwent arthroscopic examination and cartilage harvesting of the knee. Chondrocytes were then cultured in plasma and a second operation was undertaken approximately four weeks later to repair the ruptured ACL with hamstring graft and to implant the chondrocytes via formal arthrotomy. Patients then underwent a graduated rehabilitation program and were reviewed at 6 and 12 months. Functional measurements were made using the Bentley functional scale and the modified Cincinnati rating system, with pain measured on a visual analogue scale. All patients also underwent formal clinical examination at each review. Results: 4 out of the 5 patients reported an improvement in pain as measured on visual analogue scale, with 1 patient reporting no difference. 4 patients had stable knees as determined by negative anterior draw, negative Lachman’s test and negative pivot shift test; one patient showed improvement, but remained pivot shift positive. Improvements in Bentley scores were noted in 3 patients. Cincinnati scores were markedly improved in 3 patients and slightly improved in the remaining 2 patients. The only operative complications were a traction neuropraxia to the saphenous nerve of one patient requiring no treatment and a manipulation under anaesthesia for poor mobilisation in another patient, which was successful in improving range of movement. A further patient required arthroscopic trimming of the cartilage graft which had overgrown; this was also successful. Conclusion: Symptomatic cartilage defects and ACL deficiency may co-exist in many patients and represent a treatment challenge. Our early results suggest that a combined ACL and ACI repair is a viable option in this group of patients and should reduce the anaesthetic and operative risks of a two-stage repair. More patients and longer follow up will be required to fully assess this technique

Introduction and Aims: The aim of this study was to use biological, functional and radiographic evaluation to demonstrate that cultured autologous chondrocytes implanted using a type I/III collagen membrane leads to regeneration of hyaline-like articular cartilage in the knee. Method: Approximately 70,000 knee arthroscopies are performed every year in Australia; 60% involve chondral surface defects. Three regenerative autologous cell therapy techniques have been used in Australia to treat full thickness chondral lesions:. periostial-covered autologous chondrocyte implantation (PACI);. collagen-covered autologous chondrocyte implantation (CACI);. matrix-induced autologous chondrocyte implantation (MACI). The team at the University of Western Australia has concentrated on CACI and MACI techniques because of concerns over fibroblast formation and hypertrophy with PACI. Definitive evidence regarding the role of the membrane in enhancing chondrocyte-mediated cartilage regeneration is lacking. Results: The series consists of a total of 71 patients who had failed previous surgical treatment prior to definitive collagen-covered ACI (32 implantations in 31 patients) or MACI (43 implantations in 40 patients). Biological, functional and radiographic evaluations were conducted pre-operatively, and post-operatively in order to determine the success of integration of implanted chondrocytes and categorise the level of restoration in knee joint function. Post-operative MRI scans at three months show oedematous tissue at the defect sites, contrasting with the fluid-filled defects seen pre-operatively. MRI scans at one, two and three years (collagen-covered) and one year (MACI) show normal cartilage signal. Apopototic test of chondrocytes before implantation showed that viability of chondrocytes was over 85% where apopototic rate of chondrocytes was less than 2%. Six-minute walk test and KOOS results indicate improved functional capacity following collagen covered and MACI. Conclusion: Results from this clinical study indicate that the use of a type I/III collagen membrane in conjunction with ACI is a valid new approach for the treatment of chondral defects. Results from radiographic, functional and biological evaluations are encouraging. Ongoing follow-up will reveal the durability of reconstructions with CACI and MACI

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.

Autologous Chondrocyte Implantation’ (ACI) is a cartilage repair technique that involves implantation of cultured chondrocytes beneath a membrane of autologous periosteum. In this study a porcine biodegradable membrane was also used to assess its effectiveness. The aim is to restore articular cartilage to symptomatic defects, rather than initiating a fibrocartilagenous repair. We undertook a prospective study of 125 consecutive patients who underwent ACI. Average age at the time of surgery was 30. 9 years (range 14 – 49), 55% of patients were male. The average size of the defect was 4. 35 cm². 44% of defects were attributable to known traumatic incidents, 2 1 % had osteochondritis dessicans, 18% chondromalacia patella, 12% had defects of unknown aetiology and 5% other. The average duration of symptoms prior to this surgery was 7. 16 years. The mean number of previous operations (excluding arthroscopies) was 1. 6. Only 9 patients had no previous major surgery to the affected knee. 44% had defects of the medial femoral condyle, 31% patella, 20% lateral femoral condyle and 5% had a trochlea lesion. 26% of the defects were covered with periosteum and 74% with a porcine collagen membrane (chondrogide). Minimum follow-up was six months, 70 patients had minimum follow-up of one year. Mean follow-up 18 months. Patients were assessed using Modified Cincinnati and Stanmore Functional rating systems, visual analogue scores and clinical evaluation. Arthroscopy and biopsy was performed at one year and the repair assessed using the International Cartilage Research Society grading system. At one year follow-up overall 41 % patients had an excellent result, 48% good, 8% fair and 3% poor. For defects of the medial femoral condyle, 88% had a good or excellent result, 85% for the lateral femoral condyle and 80% for the patella. 61 patients were arthroscopically assessed at one year. 50/61 (82%) demonstrated ICRS grade 1 or 2 repair. Healing of the defect occurred with either a periosteum or chondrogide defect cover. Results at one year suggest that ACI is a successful articular cartilage repair technique in selected patients. Long-term follow-up is required to assess the durability of the repair

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

Introduction Talar dome lesions are a common accompaniment of ankle injury resulting in ongoing symptoms and functional disability with current management resulting in fibrocartilaginous repair and failure to reconstitute the articular surface. In this study, the application of autologous chondrocyte implantation (ACI) for talar dome lesions was evaluated. Methods Between August 2001 and February 2003, eight patients with osteochondral lesions of the talus were treated with ACI. All patients underwent initial arthroscopy to harvest healthy chondrocytes for cultivation. Cells were re-implanted after three to four weeks, with a medial or lateral malleolar osteotomy using a periosteal patch harvested from the distal tibia. Post-operatively, early ankle motion was allowed but non-weight bearing advised until union of osteotomy. Clinical assessment was pre-operatively and at three, six, nine, and 12 months post-operatively. Second-look arthroscopy with biopsy for histological examination was performed at removal of internal fixation. Four males and four females with a mean age of 40 years (range 22 to 59) are presented. Pre and postoperative clinical evaluation was done using the American Orthopaedic Foot and Ankle Society Hindfoot Score. Results The mean pre-operative score was 58.4 (range 26 to 97); at three months, it was 62 (range 32 to 84); at six months 70.6 (range 66 to 92); at nine months 79 (range 66 to 92) and at 12 months 81.5 (range 79 to 84). MRI done in four patients at three months post-ACI showed good fill in three and slight over fill in one. Minimal subchondral edema was evident in one patient. Two patients with MRI 12 months post-ACI also revealed good fill with residual bone marrow oedema. Second-look arthroscopy and biopsy at implant removal in five patients were done at a mean of six months (range 2.5 to 9) post-ACI. Arthroscopy showed the transplants were level with the surrounding tissue. Four patients had biopsies showing hyaline-like cartilage which has all the properties of normal hyaline except for the increased cell density while one biopsy revealed fibro-hyaline tissue. Marginal biopsies taken demonstrated integration of neo-cartilage to adjacent cartilage. Conclusions This study although with a limited sample, demonstrates the viability of ACI as treatment for osteochondral defects of the talus. Short-term results demonstrated clinical improvement from pre-operative to post-operative condition compatible with findings at second-look arthroscopy and histologic examination

Introduction and Aims: To determine the efficacy of autologous chondrocyte implantation (ACI) in treating focal chondral defects of the knee, we reviewed the two-year treatment outcome of ACI in 53 patients through clinical evaluation, MRI, second-look arthroscopy and core biopsies obtained. Method: From November 2000 to December 2003, 54 consecutive knees with 72 focal chondral defects (grade III or IV by modified Outerbridge) were treated with ACI using the Peterson periosteal patch technique. In this method, an initial arthroscopy was carried out to confirm the suitability for repair and when appropriate, cells were harvested either from the margins of the lesion, the intercondylar notch or both. The harvested cells were proliferated in vitro. Three to four weeks later, the cells were implanted in the defect with a medial or lateral parapatellar arthrotomy approach. A standardised post-operative rehabilitation protocol was carried out depending on the site of the lesion or lesions. Results: Improvement in mean subjective score from pre-operative (37.6) to 12 months (56.4) and 24 (60.1) months post-ACI were observed. Knee function levels also improved (86% ICRS III/IV to 66.6% I/II) from pre-operative period to 24 months post-implantation. Objective IKDC score of A or B were observed in 88% pre-operatively. This decreased to 67.9% at three months before improving to 92.5% at 12 months and 94.4% at 24 months post-implantation. Transient deterioration in all these clinical scores was observed at three months before progressive improvement became evident. MRI studies demonstrated 75.3% with at least 50% defect fill, 46.3% with near normal signal, 68.1% with mild/no effusion and also 66.7% with mild/no underlying bone marrow edema at three months. These values improved to 94.2%, 86.9%, 91.3% and 88.4% respectively at 12 months. At 24 months, further improvement to 97%, 97%, 95.6% and 92.6% respectively were observed. Second-look arthroscopy carried out in 22 knees (32 lesions) demonstrated all grafts to be normal / nearly normal based on the International Cartilage Repair Society (ICRS) visual repair assessment while core biopsies from 20 lesions demonstrated 13 (65%) grafts to have hyaline / hyaline-like tissue. Conclusion: Improvement in clinical and MRI findings obtained from second-look arthroscopy and core biopsies evaluated indicate that, at 24 months post-ACI, the resurfaced focal chondral defects of the knee remained intact and continued to function well

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.

Optimal treatment for symptomatic talus Osteochondral Lesions (OCLs) where primary surgical techniques have failed has not been established. Recent advances have focussed on biological repair such as Autologous Chondrocyte Implantation (ACI) however funding for this treatment is limited. Stem cell therapy in the ankle has not been assessed. The purpose of this pilot study was to evaluate the safety and efficacy of stem cell therapy in the treatment of ankle OCLs. The study was approved by the new procedures committee. Between January 2015 and December 2016, 26 patients, mean age of 36 years (range 16–58 years) with persisting disabling symptoms underwent Complete Cartilage Regeneration (CCR) using stem cells for failed primary treatment for ankle OCLs. Treatment involved iliac crest bone marrow aspiration, centrifugation to obtain bone marrow concentrate (BMC), and then injection of the BMC combined with hyaluronic acid into the OCL. Any necessary additional procedures, e.g. bone grafting or lateral ligament reconstruction were also undertaken. In 18 patients the lesion was on the medial talar dome, in 5 the lateral talar dome, 2 multiple, 1 tibial plafond. The Manchester-Oxford Foot Questionnaire (MOXFQ) was utilised to assess outcome. Average pre-operative MOXFQ scores were Walking dimension −78, Pain dimension − 65, and Social dimension − 64.2. Average 3 month post-operative MOXFQ scores were Walking − 54.8, Pain − 35.4, Social − 38.9. Average 6 month post-operative MOXFQ scores were Walking − 34.4, Pain − 35.4, Social − 28. Two patients from the beginning of the series had AOFAS scores only which improved from an average of 55 pre-operatively to 76 post-operatively. No early complications were noted. We conclude that CCR treatment is a safe treatment for talus OCLs in patients who have failed primary treatment. The procedure avoids two-stage surgery of ACI in some patients without large cysts. The early clinical outcome is favourable with no complications noted. Longer term follow-up is required

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).

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

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

The 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%

The high prevalence of osteoarthritis (OA), as well as the current lack of disease-modifying drugs for OA, has provided a rationale for regenerative medicine as a possible treatment modality for OA treatment. In this editorial, the current status of regenerative medicine in OA including stem cells, exosomes, and genes is summarized along with the author’s perspectives. Despite a tremendous interest, so far there is very little evidence proving the efficacy of this modality for clinical application. As symptomatic relief is not sufficient to justify the high cost associated with regenerative medicine, definitive structural improvement that would last for years or decades and obviate or delay the need for joint arthroplasty is essential for regenerative medicine to retain a place among OA treatment methods.

Cite this article: Bone Joint Res 2021;10(2):134–136.

Chondral injuries of the knee are extremely common and present a unique therapeutic challenge due to the poor intrinsic healing of articular cartilage. These injuries can lead to significant functional impairment. There are several treatment modalities for articular osteochondral defects, one of which is autologous chondrocyte implantation. Our study evaluates the mid to long term functional outcomes in a cohort of 828 patients who have undergone an autologous chondrocyte implantation procedure (either ACI or MACI), identifying retrospectively factors that may influence their outcome. The influence of factors including age, sex, presence of osteoarthritis and size and site of lesion have been assessed individually and with multivariate analysis. All patients were assessed using the Bentley Functional Score, Visual Analogue Score and the Cincinnati Functional Score. Assessment were performed pre-operatively and of their status in 2010. The longest follow-up was 12 years (range 24 to 153 months) with a mean age of 34 years at time of procedure. The mean defect size was 409 mm. 2. (range 64 to 2075 mm. 2. ). The distribution of lesions was 51% Medial Femoral Condyle, 12.5% Lateral Femoral Condyle, 18% Patella (single facet), 5% Patella (Multifacet) and 6% Trochlea. 4% had cartilage transplant to multiple sites. High failure rates were noted in those with previous cartilage regenerative procedures or evidence of early osteoarthritis and those with transplantation to multiple sites. Autologous chondrocyte implantation is an effective method of decreasing pain and increasing function, however patient selection plays clear role in the success of such procedure

We assessed 224 patients treated with Autologous Chondrocyte Implantation performed 10–20 years ago (average 12.8 years). Average age at the time of the implantation was 33.3 years. Average size of lesion was 5.3 cm2 (range 0.6–16), while 55 patients sustained multiple lesions. The participants filled out five questionnaires. Lysholm score, Tegner-Walgren, modified Cincinnati (Noyes), Brittberg score, and KOOS were assessed. In addition, the patients were asked to grade their current situation compared to their previous follow up as better, worse of unchanged. Finally, they were asked if they would do the operation again, answering with yes or no. The patients were divided into groups according to the location and characteristics of the cartilage lesions, or concomitant surgeries during the ACI. Assessment of the outcomes reveals a significant improvement in all groups, compared with the preoperative values. There is no other study assessing a cartilage treatment with such a long follow up. According to the results of that study, autologous chondrocyte implantation seems to be an effective and durable solution for the treatment of large full thickness cartilage and osteochondral lesions of the knee joint

We aimed to assess the long term results of patients who underwent Autologous Chondrocyte Implantation (ACI) for osteochondral lesions of the talus. Between 1998 and 2006, 28 patients underwent ACI for osteochondral lesions of the talus. All these patients were prospectively reviewed and assessed for long term results. Outcomes were assessed using satisfaction scores, Mazur ankle score and the AOFAS score, and Lysholm knee score for donor site morbidity. The 28 patients who underwent the procedure included 18 males and 10 females. Follow up ranged from 1–9 years. In all patients, there was an improvement in the Mazur and AOFAS ankle scores and the Lysholm scores showed minimal donor site morbidity. Improvement in ankle score was independent of age and gender. The better the pre-op score the less the difference in post-op ankle scores. Patients were unlikely to benefit with pre-op ankle scores over 75. The mid to long term results of ACIs in the treatment of localised, contained cartilage defects of the talus are encouraging and prove that it is a satisfactory treatment modality for symptomatic osteochondral lesions of the talus. Complications are limited. However, in view of limited number of patients, a multi-centre randomised controlled study is required for further assessment

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

Recently biodegradable synthetic scaffolds (Trufit plug) have provided novel approach to the management of chondral and osteochondral lesions. The aim of this study was to assess our 2 year experience with the Trufit plug system. 22 patients aged 20 to 50 years old all presenting with knee pain over a 2 year period were diagnosed either by MRI or arthroscopically with an isolated chondral or osteochondral lesion and proceeded to either arthroscopic or mini arthrotomy Trufit plug implantation. In 5 patients plug implantation was undertaken along with ACL reconstruction (3), medial meniscal repair (1) and contralateral knee OCD screw fixation (1). Pre and post operative IKDC scores were obtained to assess change in knee symptoms and function. At a mean follow up of 15 months (range 2 – 24 months) improved IKDC scores were achieved with the scores improving with time. 2 patients have had a poor result and have had further surgery for their chondral lesions. One patient had failure of graft incorporation at second look arthroscopy and went onto to have a good result after ACI. The second patient had good graft incorporation on second look but had progression of osteoarthritic degeneration throughout the other compartments of the knee which were not initially identified at the time of Trufit plugging. We conclude that Trufit plug is an alternative method for managing isolated chondral and osteochondral lesions of the knee which avoids harvest site morbidity or the need for staged surgery

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

Chondral injuries of the knee are extremely common and present a unique therapeutic challenge due to the poor intrinsic healing of articular cartilage. These injuries can lead to significant functional impairment. There are several treatment modalities for articular osteochondral defects, one of which is autologous chondrocyte implantation. Our study evaluates the mid to long term functional outcomes in a cohort of 828 patients who have undergone an autologous chondrocyte implantation procedure (either ACI or MACI), identifying retrospectively factors that may influence their outcome. The influence of factors including age, sex, presence of osteoarthritis and size and site of lesion have been assessed individually and with multivariate analysis. All patients were assessed using the Bentley Functional Score, Visual Analogue Score and the Cincinnati Functional Score. Assessment were performed pre-operatively and of their status in 2010. The majority of patients had several interim scores performed at varying intervals. The longest follow-up was 12 years (range 24 to 153 months) with a mean age of 34 years at time of procedure. The mean defect size was 486 mm2 (range 64 to 2075 mm2). The distribution of lesions was 51% Medial Femoral Condyle, 12.5% Lateral Femoral Condyle, 18% Patella (single facet), 5% Patella (Multifacet) and 6% Trochlea. 4% had cartilage transplant to multiple sites. 30% failed following this procedure at a mean time of 72 months. 52% patients stated a marked improvement in their functional outcomes within the first two years. 49% stated an excellent result following their procedure. High failure rate was noted in those with previous cartilage regenerative procedures, transplants occurring on the patella, particularly if involving multifacets. Multiple site cartilage transplantation was also associated with a high failure rate. Autologous chondrocyte implantation is an effective method of decreasing pain and increasing function, however patient selection plays clear role in the success of such procedure