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.

Aims. The aims of this study were to develop an automatic system capable of calculating four radiological measurements used in the diagnosis and monitoring of cerebral palsy (CP)-related hip disease, and to demonstrate that these measurements are sufficiently accurate to be used in clinical practice. Methods. We developed a machine-learning system to automatically measure Reimer’s migration percentage (RMP), acetabular index (ACI), head shaft angle (HSA), and neck shaft angle (NSA). The system automatically locates points around the femoral head and acetabulum on pelvic radiographs, and uses these to calculate measurements. The system was evaluated on 1,650 pelvic radiographs of children with CP (682 females and 968 males, mean age 8.3 years (SD 4.5)). Each radiograph was manually measured by five clinical experts. Agreement between the manual clinical measurements and the automatic system was assessed by mean absolute deviation (MAD) from the mean manual measurement, type 1 and type 2 intraclass correlation coefficients (ICCs), and a linear mixed-effects model (LMM) for assessing bias. Results. The MAD scores were 5.7% (SD 8.5%) for RMP, 4.3° (SD 5.4°) for ACI, 5.0° (SD 5.2°) for NSA, and 5.7° (SD 6.1°) for HSA. Overall ICCs quantifying the agreement between the mean manual measurement and the automatic results were 0.91 for RMP, 0.66 for ACI, 0.85 for NSA, and 0.73 for HSA. The LMM showed no statistically significant bias. Conclusion. The results showed excellent agreement between the manual and automatic measurements for RMP, good agreement for NSA, and moderate agreement for HSA and ACI. The performance of the system is sufficient for application in clinical practice to support the assessment of hip migration based on RMP. The system has the potential to save clinicians time and to improve patient care by enabling more comprehensive, consistent, and reliable monitoring of hip migration in children with CP. Cite this article: Bone Joint J 2025;107-B(1):124–132

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. 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

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

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

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

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)

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)

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