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Summary: Objective: Spherox (CO.DON AG) is an autologous chondrocyte implantation (ACI) product, consisting of spheroids of human autologous matrix-associated chondrocytes. The tendency of primary chondrocytes to dedifferentiate during cultivation and the high biologic variability caused by the autologous nature of the starting material makes it challenging to design a manufacturing process that performs consistently and delivers products that meet their intended function and the high quality criteria for cell-based ATMPs. The current study was submitted during the European authorization procedure, and addresses the requirement to justify the operational ranges of the manufacturing process using clinical data. Methods: In order to define the operational ranges, statistical correlation analyses were conducted between process parameters and clinical improvement data of 120 patients from Phase II and III treated with ACI (KOOS score, 1 year follow-up). Results: This approach identified cell culture time as a critical process parameter that negatively correlates with the product's efficacy. Subsequent analyses of the Phase III patients that were treated with chondrocyte spheroids that have been manufactured with shorter monolayer and spheroid cultivation times showed a higher average clinical improvement as well as a higher responder rate compared to the total group. In addition, retrospective analyses demonstrated superiority for the treatment with short-cultivated chondrocyte spheroids over micro-fracture treatment. Conclusion: These findings underscore the need to use clinical data to optimize the manufacturing process for autologous cell-based therapies. We expect that restricting the cultivation times during manufacturing minimizes the production of suboptimal batches, thus ensuring an efficacious product.

Deutlich gestiegene Implantationszahlen unikondylärer Knieprothesen bei der Gonarthrose lassen trotz insgesamt guter Überlebensraten einen zukünftigen Anstieg von Revisionseingriffen erwarten. Die Versagensgründe nach unikondylären Knieprothesen unterscheiden sich hinsichtlich Ursache und Häufigkeitsverteilung deutlich von bikondylären Prothesen. Neben einer aseptischen Lockerung stellt häufig das Fortschreiten der Arthrose im unversorgten Kompartiment eine Indikation für die Wechseloperation dar. Die Revision einer unikondylären Knieprothese wird in der Regel auf eine bikondyläre Knieprothese erfolgen. [ABSTRACT FROM AUTHOR]

Purpose: Bone marrow stimulation is a common treatment for full-thickness cartilage defects in the hip joint. However, common procedures may result in poor fibrous repair tissue and changes to the subchondral anatomy. This study investigated the clinical outcome of a cohort of International Cartilage Repair Society (ICRS) grades 3 and 4 cartilage defects treated with bone marrow stimulation compared to those who received simple debridement/chondroplasty., Methods: In this retrospective registry study, 236 patients with uni-focal acetabular chondral lesions of the hip up to 400 mm² (mean 177.4 ± 113.4 mm²) and of ICRS grade ≥3 with follow-up of at least 12 months (mean 33.2 ± 15.3 months) were included. Eighty-one patients underwent bone marrow stimulation (microfracture: n = 44, abrasion: n = 37) besides treatment of the underlying pathology, 155 patients underwent defect debridement/chondroplasty. The patient-reported outcome was measured using the International Hip Outcome Tool 33 (iHOT33) score and the Visual Analogue Scale (VAS) for pain., Results: iHOT33 and VAS both improved highly statistically significantly (p < 0.001) in the debridement group after 6, 12, 24, 36 and 60 months compared to the preoperative scores, whereas iHOT33 and VAS after microfracture or abrasion did not show statistically significant changes over time. Twenty-four and sixty months postsurgery the debridement group revealed significant higher scores in the iHOT33 compared to the bone marrow stimulation groups., Conclusion: Patients with chondral lesions of the hip ≤400 mm 2 sustainably benefit from arthroscopic debridement under preservation of the subchondral bone plate in terms of functional outcome and pain in contrast to patients treated with bone marrow stimulation. These findings discourage the currently recommended use of microfracture in the hip joint., Level of Evidence: Level III., (© 2024 The Author(s). Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Purpose: To compare clinical outcome parameters between labral debridement and repair by analyzing the dataset of a multinational registry., Methods: The data are based on the hip module of the German Cartilage Registry (KnorpelRegister DGOU). The register included patients designated for cartilage or femoroacetabular impingement surgery (up to July 1, 2021; n = 2725). The assessment consisted of the patient's characteristics, the type of labral treatment, the length of labral therapy, the pathology, the grade of cartilage damage, and the type of performed approach. The clinical outcomes were documented by the international hip outcome tool via an online platform. Separated Kaplan-Meier analyses were used for total hip arthroplasty (THA)-free survival rates., Results: The debridement group (n = 673) showed a mean score increase of 21.9 ± 25.3 points. The repair group (n = 963) had a mean improvement of 21.3 ± 24.6 (P > .05). The 60-month THA-free survival rate was 90% to 93% for both groups (P > .05). A multivariance analysis showed that the grade of cartilage damage was the only independent statistically significant factor (P = .002-.001) influencing patients' outcomes and THA-free survival., Conclusions: Labral debridement and repair led to good and reliable results. However, these results should not be interpreted with the conclusion that the cheaper and technically easier labral debridement is the recommended treatment due to comparable results in the present study. The clinical outcome and the THA-free survival seemed to be more influenced by the grade of cartilage damage., Level of Evidence: Level III, retrospective comparative therapeutic trial., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Methods: Peer-reviewed literature was analyzed regarding different topics relevant to osteochondral lesions of the talus (OLTs) treatment. This process concluded with a statement for each topic reflecting the best scientific evidence available for a particular diagnostic or therapeutic concept, including the grade of recommendation. Besides the scientific evidence, all group members rated the statements to identify possible gaps between literature and current clinical practice., Conclusion: In patients with minimal symptoms, OLT progression to ankle osteoarthritis is unlikely. Risk factors for progression are the depth of the lesion on MRI, subchondral cyst formation, and the extent of bone marrow edema. Conservative management is the adaptation of activities to the performance of the ankle joint. A follow-up imaging after 12 months helps not to miss any progression. It is impossible to estimate the probability of success of conservative management from initial symptoms and imaging. Cast immobilization is an option in OLTs in children, with a success rate of approximately 50%, although complete healing, estimated from imaging, is rare. In adults, improvement by conservative management ranges between 45% and 59%. Rest and restrictions for sports activities seem to be more successful than immobilization. Intra-articular injections of hyaluronic acid and platelet-rich plasma can improve pain and functional scores for more than 6 months. If 3 months of conservative management does not improve symptoms, surgery can be recommended.

Purpose: Articular cartilage defects are a prevalent consequence of femoroacetabular impingement (FAI) in young active patients. In accordance with current guidelines, large chondral lesions of the hip joint over 2 cm 2 are recommended to be treated with matrix-associated, autologous chondrocyte transplantation (MACT); however, the conditions in the hip joint are challenging for membrane-based MACT options. Injectable MACT products can solve this problem. The purpose of the trial was to assess clinical and radiological outcomes 24 months after injectable MACT of focal chondral lesions caused by FAI., Methods: We present data of 21 patients with focal cartilage defects of the hip [3.0 ± 1.4 cm 2 (mean ± SD)], ICRS Grade III and IV caused by CAM-type impingement, who underwent arthroscopic MACT (NOVOCART ® Inject) and FAI correction. The outcome was evaluated with the patient-reported outcome instruments iHOT33 and EQ-5D-5L (index value and VAS), whilst graft morphology was assessed based on the MOCART score over a follow-up period of 24 months., Results: The iHOT33 score increased significantly from 52.9 ± 21.1 (mean ± SD) preoperatively to 85.8 ± 14.8 (mean ± SD; p < 0.0001) 24 months postoperatively. The EQ-5D-5L index value ( p = 0.0004) and EQ-5D VAS ( p = 0.0006) showed a statistically significant improvement as well. MRI evaluation after 24 months showed successful integration of the implant in all patients with a complete defect filling in 11 of 14 patients., Conclusions: Injectable MACT for the treatment of full-thickness chondral lesions of the hip joint due to FAI in combination with FAI correction improved symptoms, function, and quality of life in the treated cohort. Alongside the treatment of the underlying pathology by the FAI correction, the developed cartilage defect can be successfully repaired by MACT, which is of considerable clinical relevance.

Purpose: To evaluate the safety and efficacy of matrix-associated autologous chondrocyte implantation (ACI) using spheroids in comparison to arthroscopic microfracture for the treatment of symptomatic cartilage defects of the knee., Methods: In a prospective multicenter-controlled trial, patients aged between 18 and 50 years, with single symptomatic focal cartilage defects between 1 and 4 cm 2 (mean 2.6 ± 0.8, median 2.75, range 1.44-5.00) in the knee were randomized to treatment with ACI with spheroids (n = 52) or microfracture (n = 50). Primary clinical outcome was assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Analyses were performed in a defined hierarchical manner where outcomes of ACI were first compared to baseline values followed by a comparison to the microfracture group with repeated-measures ANCOVA with a non-inferiority approach. Subgroup analyses were performed to investigate the influence of age and defect size on the overall KOOS. Secondary clinical outcomes were the magnetic resonance observation of cartilage repair tissue (MOCART), modified Lysholm score and International Knee Documentation Committee (IKDC) examination form. Safety data focused on adverse events. Here the 5 years results are presented at which there were 33 observed cases in the ACI group and 30 in the microfracture group., Results: The overall KOOS and its five subscores were significantly improved compared to baseline for both the ACI and microfracture group. Non-inferiority of ACI to microfracture was confirmed for the overall KOOS and the subscores, while for the subscores activities of daily living, quality of life and sports and recreation of the threshold for superiority was passed. In the ACI group, a notably more rapid initial improvement of the KOOS was found at three months for the older age group compared to the younger age group and the microfracture group. No other differences were found based on age or defect size. In addition, clinical improvement was found for the MOCART, modified Lysholm and IKDC examination form both the ACI and microfracture group. No safety concern related to either treatment was observed., Conclusion: This study confirms the safety and efficacy of matrix-associated ACI with spheroids at a mid to long-term follow-up. Non-inferiority of ACI to microfracture was confirmed for the overall KOOS and all subscores, while superiority was reached for the subscores activities of daily living, quality of life and sports and recreation in the ACI group. This underlines the importance of ACI for the young and active patients., Level of Evidence: I., (© 2022. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

The Working Group of the German Orthopedic and Trauma Society (DGOU) on Tissue Regeneration has published recommendations on the indication of different surgical approaches for treatment of full-thickness cartilage defects in the knee joint in 2004, 2013 and 2016. Based upon new scientific knowledge and new developments, this recommendation is an update based upon the best clinical evidence available. In addition to prospective randomised controlled clinical trials, this also includes studies with a lower level of evidence. In the absence of evidence, the decision is based on a consensus process within the members of the working group.The principle of making decision dependent on defect size has not been changed in the new recommendation either. The indication for arthroscopic microfracturing has been reduced up to a defect size of 2 cm 2 maximum, while autologous chondrocyte implantation is the method of choice for larger cartilage defects. Additionally, matrix-augmented bone marrow stimulation (mBMS) has been included in the recommendation for defects ranging from 1 to 4.5 cm 2 . For the treatment of smaller osteochondral defects, in addition to osteochondral transplantation (OCT), mBMS is also recommended. For larger defects, matrix-augmented autologous chondrocyte implantation (mACI/mACT) in combination with augmentation of the subchondral bone is recommended., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Objective: According to current recommendations, large cartilage defects of the hip over 2 cm 2 are suggested to undergo autologous chondrocyte transplantation (ACT), while small defects should be treated with microfracture. We investigated if patients with small chondral defects of the hip joint (≤100 mm 2 ) actually benefit from microfracture., Design: In this retrospective multicenter cohort study 40 patients with focal acetabular cartilage defects smaller than 100 mm 2 and of ICRS grade ≥2 caused by femoroacetabular impingement were included. Twenty-six unrandomized patients underwent microfracture besides treatment of the underlying pathology; in 14 patients cartilage lesions were left untreated during arthroscopy. Over a mean follow-up of 28.8 months patient-reported outcome was determined using the iHOT33 (international hip outcome tool) and the VAS (visual analog scale) for pain., Results: The untreated group showed a statistically significant improvement of the iHOT33 after 12 ( p = 0.005), 24 ( p = 0.019), and 36 months ( p = 0.002) compared to the preoperative score, whereas iHOT33 in the microfracture group did not reveal statistically significant changes over time. There was no significant difference between both groups on any time point. Regarding pain both groups did not show a significant improvement over time in the VAS., Conclusion: The subjective outcome of patients with small cartilage defects of the hip (≤100 mm 2 ) improves 12 months after arthroscopic FAIS surgery without any cartilage treatment. However, no improvement could be seen after microfracture. Therefore, a reserved surgical treatment for small cartilage defects of the hip under preservation of the subchondral bone is recommended especially if a simultaneous impingement correction is performed., Competing Interests: The authors declare no conflict of interest.

Background: The treatment of femoroacetabular impingement syndrome (FAIS) and its sequelae has changed over the past 20 years based on a steadily increasing understanding of the condition and improvements in surgical techniques., Question: What is the evidence for the treatment of FAIS?, Methods: Analysis of the available literature, structured review, and discussion of the relevant literature., Results: The treatment of FAIS has evolved over time through several phases. In the first phase, the clinical picture and its open treatment by surgical hip dislocation were described. Subsequently, the first comparative studies between open, mini-open, and arthroscopic therapy were published. After development of disease-specific patient-reported outcome measurement systems, the concerns of the young, more active patient population could be captured. In recent years, prospective randomized controlled trials comparing conservative versus surgical therapy of FAIS have been published, showing the superiority of surgical treatment and also the need to strengthen evidence-based research especially in the field of conservative treatment of FAIS., Conclusion: The pathomechanism and sequelae of FAIS have been increasingly studied scientifically in recent years. The superiority of a particular surgical technique cannot be demonstrated; the arthroscopic technique has a lower complication rate and a faster convalescence. Clinically important outcome measures are also becoming increasingly established in the therapy of FAIS to capture the clinical relevance for the individual., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

This study aims to report on a prospectively collected, multicenter database of patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAI) and concomitant cartilage damage (according to the International Cartilage Repair Society) and to assess the outcome-affecting parameters. In the study, 353 hips with up to 24 months' follow-up were assessed by iHOT-33 scoring and achievement of the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) levels. Multiple and binary regression analyses were performed to identify factors related to (un-) favorable outcomes and to assess their clinical relevance with regard to achieving the MCID and PASS. Multiple regression yielded the parameters of male sex ( p = 0.022) and lower body mass index (BMI) ( p = 0.019) at 6 months, lower BMI ( p = 0.022) and younger age ( p = 0.022) at 12 months, and younger age at 24 months ( p = 0.039) to be significantly associated with higher iHOT scoring. Male sex ( p = 0.019) and lower BMI ( p = 0.018) were significantly correlated with achievement of the PASS in binary regression at 6 months, whereas at 12 ( p = 0.010) and at 24 ( p = 0.003) only younger age was shown to be significantly correlated. None of the parameters was statistically associated with achievement of the MCID. As the parameters of younger age, male sex, and lower BMI were identified as temporarily correlated with a preferable outcome in general and with achievement of the PASS in particular, these findings help to preoperatively identify factors associated with (un-) favorable therapy results.

FAIS is a well-defined clinical entity with morphological alterations, whether constitutional or acquired, that can lead to damage of the labrum and acetabular cartilage following distinct injury patterns with subsequent osteoarthritis. The combination pathology of cam and pincer deformity is the most common variant. The characteristic changes of the chondrolabral complex that are caused by the dysplasia differ from these FAIS changes. Furthermore, femoral torsion also has an impact on the clinical appearance of Cam- or Pincer-FAIS., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Matrix-associated autologous chondrocyte implantation (ACI) is a well-established treatment for cartilage defects. High-level evidence at midterm follow-up is limited, especially for ACI using spheroids (spherical aggregates of ex vivo expanded human autologous chondrocytes and self-synthesized extracellular matrix)., Purpose: To assess the safety and efficacy of 3-dimensional matrix-associated ACI using spheroids to treat medium to large cartilage defects on different locations in the knee joint (patella, trochlea, and femoral condyle) at 5-year follow-up., Study Design: Cohort study; Level of evidence, 2., Methods: A total of 75 patients aged 18 to 50 years with medium to large (4-10 cm 2 ), isolated, single cartilage defects, International Cartilage Repair Society grade 3 or 4, were randomized on a single-blind basis to treatment with ACI at 1 of 3 dose levels: 3 to 7, 10 to 30, or 40 to 70 spheroids/cm 2 of defect size. Outcomes were assessed via changes from baseline Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee score, and modified Lysholm assessments at 1- and 5-year follow-up. Structural repair was evaluated using MOCART (magnetic resonance observation of cartilage repair tissue) score. Treatment-related adverse events were assessed up to 5 years for all patients. The overall KOOS at 12 months was assessed for superiority versus baseline in a 1-sample, 2-sided t test., Results: A total of 73 patients were treated: 24 in the low-dose group, 25 in the medium-dose group, and 24 in the high-dose group. The overall KOOS improved from 57.0 ± 15.2 at baseline to 73.4 ± 17.3 at 1-year follow-up ( P < .0001) and 76.9 ± 19.3 at 5-year follow-up ( P < .0001), independent of the applied dose. The different defect locations (patella, trochlea, and weightbearing part of the femoral condyles; P = .2216) and defect sizes ( P = .8706) showed comparable clinical improvement. No differences between the various doses were observed. The overall treatment failure rate until 5 years was 4%. Most treatment-related adverse events occurred within the first 12 months after implantation, with the most frequent adverse reactions being joint effusion (n = 71), arthralgia (n = 14), and joint swelling (n = 9)., Conclusion: ACI using spheroids was safe and effective for defect sizes up to 10 cm 2 and showed maintenance of efficacy up to 5 years for all 3 doses that were investigated., Registration: NCT01225575 (ClinicalTrials.gov identifier); 2009-016816-20 (EudraCT number)., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: The present study was funded by CO.DON. A.H. has received consulting fees from CO.DON. P.N. has received consulting fees from CO.DON and education support from Aesculap, Arthrex, Geistlich, Moximed, Stryker, and Medi. W.Z. has received consulting fees from CO.DON. S.F. has received consulting fees from Arthrex and Bauerfeind. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Objective: Matrix-associated autologous chondrocyte implantation (ACI) and microfracture (MF) are well-established treatments for cartilage defects of the knee. However, high-level evidence comparing microfracture and spheroid technology ACI is limited., Design: Prospective, phase III clinical trial with patients randomized to ACI ( N = 52) or MF ( N = 50). Level of evidence: 1, randomized controlled trial. Both procedures followed standard protocols. For ACI 10 to 70 spheroids/cm 2 were administered. Primary outcome measure was the Knee Injury and Osteoarthritis Outcome Score (KOOS). This report presents results for 36 months after treatment., Results: Both ACI and MF showed significant improvement over the entire 3-year observation period. For the overall KOOS, noninferiority of ACI (the intended primary goal of the study) was formally confirmed; additionally, for the subscores "Activities of Daily Living" and "Sport and Recreation," superiority of ACI over MF was shown at descriptive level. Occurrence of adverse events were not different between both treatments (ACI 77%; MF 74%). Four patients in the MF group required reoperation which was defined as treatment failure. No treatment failure was reported for the ACI group., Conclusions: Patients treated with matrix-associated ACI with spheroid technology showed substantial improvement in various clinical outcomes after 36 months. The advantages of ACI compared with microfracture was underlined by demonstrating noninferiority, in overall KOOS and superiority in the KOOS subscores "Activities of Daily Living" and "Sport and Recreation." In the present study, subgroups comparing different age groups and defect sizes showed comparable clinical outcomes.

Background: Using the database of the German Cartilage Registry (KnorpelRegister DGOU), this study aims to present patient- and joint-related baseline data in a large cohort of patients with cam-derived femoroacetabular impingement syndrome (FAI) and to detect symptom-determining factors., Materials and Methods: Requiring cam morphology as the primary pathology, 362 patients were found to be eligible for inclusion in the study. The assessment of preoperative baseline data was performed using the patient-reported outcome measure-International Hip Outcome Tool (iHOT-33). Descriptive statistics were performed to present baseline data. Univariate and multiple regression with post hoc testing were used to identify patient- and joint-related factors that might affect the preoperative iHOT-33 and its subscores, respectively., Results: The study collective's mean age was 36.71 ± 10.89 years, with 246 (68%) of them being male. The preoperative mean iHOT-33 total was 46.31 ± 20.33 with the subsection "sports and recreational activities" presenting the strongest decline (26.49 ± 20.68). The parameters "age," "sex," "body mass index" (BMI), and the confirmation of "previous surgery on the affected hip" were identified to statistically affect the preoperative iHOT-33. In fact, a significantly lower mean baseline score was found in patients aged > 40 years (p < 0.001), female sex (p < 0.001), BMI ≥ 25 kg/m 2 (p = 0.002) and in patients with previous surgery on the affected hip (p = 0.022). In contrast, the parameters defect grade and size, labral tears, and symptom duration delivered no significant results., Conclusions: A distinct reduction in the baseline iHOT-33, with mean total scores being more than halved, was revealed. The parameters "age > 40 years," "female sex," "BMI ≥ 25," and confirmation of "previous surgery on the affected hip" were detected as significantly associated with decreased preoperative iHOT-33 scores. These results help to identify symptom-defining baseline characteristics of cam-derived FAI syndrome., Trial Registration: The German Cartilage Registry is conducted in accordance with the Declaration of Helsinki and registered at germanctr.de (DRKS00005617). Registered 3 January 2014-retrospectively registered. The registration of data was approved by the local ethics committees of every participating institution. Primary approval was given by the ethics committee at the University of Freiburg (No. 105/13). https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00005617., (© 2021. The Author(s).)

Objective: To determine performance and repair kinetics of the ChonDux hydrogel scaffold for treating focal articular cartilage defects in the knee over 24 months., Design: This assessor-blinded trial evaluates ChonDux hydrogel scaffold implantation in combination with microfracture in 18 patients across 6 sites. Male and female patients 18 to 65 years of age with full-thickness femoral condyle defects 2 to 4 cm 2 in area were enrolled. Eligible patients received ChonDux treatment followed by rehabilitation. Defect volume fill was evaluated after 3, 6 (primary outcome), 12, 18, and 24 months by assessor blinded magnetic resonance imaging (MRI) analysis. Secondary outcomes were T2-weighted MRI relaxation time and patient surveys via visual analogue scale (VAS) pain and International Knee Documentation Committee (IKDC) knee function scoring., Results: ChonDux maintained durable tissue restoration over 24 months with final defect percent fill of 94.2% ± 16.3% and no significant loss of fill volume at any time points. Tissues treated with ChonDux maintained T2 relaxation times similar to uninjured cartilage between 12 and 24 months. VAS pain scoring decreased between 1 and 6 weeks, and IKDC knee function scores improved by approximately 30.1 with ChonDux over 24 months., Conclusion: ChonDux treatment is a safe adjunct to microfracture therapy and promotes stable restoration of full thickness articular cartilage defects for at least 24 months.

Aim: Cartilage defects of the patella are considered as a problematic entity. Purpose of the present study was to evaluate the outcome of patients treated with autologous chondrocyte implantation (ACI) for cartilage defects of the patella in comparison to patient with defects of the femoral condyles., Patients and Methods: 73 patients with a follow-up of 5 years have been included in this subgroup analysis of the randomized controlled clinical trial (RCT). In dependence of defect location, patients were divided into two groups [patella defects (n = 45) and femoral condyle defects (n = 28)]. Clinical outcome was evaluated by the means of the KOOS score at baseline and 6 weeks, 3, 6, 12, 18, 24, 36, 48 and 60 months following ACI., Results: "Responder rate" at 60 months (improvement from baseline of > 7 points in the KOOS score) in patients with patella defects was 86.2%. All scores showed a significant improvement from baseline. While overall KOOS score at 60 months was 81.9 (SD 18.6) points in femoral condyle defects, a mean of 82.6 (SD 14.0) was observed in patella defects (p = 0.2483)., Conclusion: ACI seems an appropriate surgical treatment for cartilage defects of the patella leading to a high success rate. In this study, the clinical outcome in patients with patellar defects was even better than the already excellent results in patients with defects of the femoral condyle even though the study included relatively large defect sizes for both groups (mean defect size 6.0 ± 1.7 and 5.4 ± 1.6 for femur and patella, respectively).

Purpose: The aim of this study was to investigate the effect of product dose in autologous chondrocyte implantation (ACI) for the treatment of full-thickness cartilage defects of the knee and to assess its influence on clinical and morphological mid-term outcome., Methods: Seventy-five patients were included in this single-blind, randomised, prospective, controlled clinical trial. Patients were assigned randomly to three different dose groups [low (3-7 spheroids/cm 2 ), medium (10-30 spheroids/cm 2 ), or high (40-70 spheroids/cm 2 )] and assessed using standardised clinical and morphological scoring systems (KOOS, IKDC, MOCART) for 4 years following the intervention., Results: The analysis population comprised 75 patients (22 women, 53 men) aged 34 ± 9 years. Defect sizes ranged from 2 to 10 cm 2 following intraoperative debridement. The assessment of the primary variable 'overall KOOS' showed a statistically significant improvement, compared with baseline, for each dose group, i.e., at baseline the mean 'overall KOOS' scores were 60.4 ± 13.6, 59.6 ± 15.4, and 51.1 ± 15.4 for the low-, medium-, and high-dose groups, respectively, and 57.0 ± 15.2 for 'all patients'. After 48 months those values improved to 80.0 ± 14.7, 84.0 ± 14.9, and 66.9 ± 21.5 in the respective dose groups and 77.1 ± 18.6 for 'all patients'. Pairwise comparisons of these dose groups did not reveal any statistically significant differences. Likewise, assessment of the subjective IKDC score revealed no statistically significant differences between the three dose groups up to the 48-month visit. However, between 12 and 48 months there was a low, but steady, improvement in the low-dose group and a substantial amelioration in the medium-dose group. The mean MOCART total scores 3 months after treatment were 59.8 ± 10.9, 64.5 ± 10.3, and 64.7 ± 9.4 for the low-, medium-, and high-dose groups, and 62.9 ± 10.3 for 'all patients'; 48 months after treatment these were 73.9 ± 13.1, 78.0 ± 12.4, and 74.3 ± 14.0 for the respective dose groups and 75.5 ± 13.1 for 'all patients'., Conclusions: Results of this study confirm the efficacy and safety of the applied "advanced therapy medicinal product"; no dose dependence was found either for the incidence or for the severity of any adverse reactions. All doses applied in the present study led to significant clinical improvement over time and can therefore be regarded as effective doses. The influence of product doses in the range investigated seems to be low and can be neglected. Thus, the authorised dose range of 10-70 spheroids/cm 2 confirmed by this clinical trial offers a broad therapeutic window for the surgeon applying the product, thereby reducing the risk of over- or underdosing., Level of Evidence: I.

Purpose: Acetabular chondral lesions are common in patients with FAI. For large full-thickness cartilage defects, arthroscopic matrix-associated autologous chondrocyte transplantation (MACT) using an injectable in situ crosslinking product is an option. Aim of the study was to evaluate clinical and MRI results 12 months after MACT of acetabular cartilage defects in FAI patients., Methods: We report data on 21 patients with a focal cartilage defect of the hip [2.97 ± 1.44 cm 2 (mean ± SD)] caused by FAI treated with an arthroscopically conducted MACT combined with FAI surgery. The results were assessed with patient-reported outcome measures (iHOT33, EQ-5D) pre- as well as post-operatively and by MRI using MOCART scoring system 6 and 12 months post-operatively., Results: The iHOT33 score improved from 52.9 ± 21.14 (mean ± SD) pre-operative to 81.08 ± 22.04 (mean ± SD; p = 0.0012) 12 months post-operatively. The lower the pre-operative iHOT33 score and the larger the defect size, the greater the observed improvement compared to pre-operative scores at 12 months. Patients showed a significant improvement in EQ-5D-5L index value (p = 0.0015) and EQ-5D VAS (p = 0.0006). MRI analysis after 12 months revealed a complete integration of the transplant in 16 of 20 patients., Conclusions: Injectable MACT is a promising minimally invasive treatment option for full-thickness cartilage defects of the hip caused by FAI. A significant improvement in symptoms and function associated with an increase in quality of life was detected in patients treated with injectable MACT combined with FAI surgery. This is of considerable clinical relevance, since, in addition to the elimination of the mechanical cause, MACT allows the successful therapy of consequential cartilage damage., Level of Evidence: Level 4, case series.

The characterization of regenerated articular cartilage (AC) can be based on various methods, as there is an unambiguous accepted criterion neither for the natural cartilage tissue nor for regenerates. Biomechanical aspects should be considered as well, leading to the need for more equivalent samples. The aim of the study was to describe a large animal model where 8 specimens of regenerated AC can be created in one animal plus the impact of two surgeries on the welfare of the animals. The usefulness of the inclusion of a group of untreated animals (NAT) was to analyzed. Based on the histological results the conditions of the regenerates were to be described and the impact on knee joints were to be explored in terms of degenerative changes of the cartilage. The usefulness of the statistical term "effect size" (ES) will be explained with histological results. We analyzed an animal model where 8 AC regenerates were obtained from one Göttingen Minipig, on both sides of the trochleae. 60 animals were divided into 6 groups of 10 each, where the partial thickness defects in the trochlea were filled with matrices made of Collagen I with or without autologous chondrocytes or left empty over the healing periods of 24 and 48 weeks. One additional control group consisting of 10 untreated animals was used to provide untouched "external" cartilage. We harvested 560 samples of regenerated tissue and "external" controls, besides that, twice the number of further samples from other parts of the joints referred to as "internal" controls were also harvested. The animals recovered faster after the 1st operation when the defects were set compared to the 2nd operation when the defects were treated. 9% of all animals were lost. Other complications were for example superficial infections, seroma, diarrhea, febrile state and an injury of a claw. The histological results of the treatments proved the robustness of the study design where we included an "external" control group (NAT) in which the animals were not operated. Comparable significant differences between treated groups and the NAT group were detected both after ½ year and after 1 year. Spontaneous regenerated AC as control revealed differences after an observation time of nearly 1 year. The impact of the treatment on cartilage adjacent to the defect as well as the remaining knee joint was low. The ES was helpful for planning the study as it is shown that the power of a statistical comparison seems to be more influenced by the ES than by the sample size. The ranking of the ES was done exemplarily, listing the results according to their magnitude, thus making the results comparable. We were able to follow the 3 R requirements also in terms of a numerical reduction of animals due to the introduction of a group of untreated animals. This makes the model cost effective. The presented study may contribute as an improvement of the standardization of large animal models for research and regulatory requirements for regenerative therapies of AC., Competing Interests: TL was involved in the presented study as statistician on behalf of the Medical Faculty Mannheim, University Heidelberg and of the research consortium QuReGe that was funded by the Federal Ministry of Education and Research, Germany (“Funktionelle Qualitätssicherung von regenerativen Gewebeersatzmaterialien für Knorpel und Meniskus (QuReGe)” to support the animal trial in terms of sample size calculation and to develop a tool for the grading of the outcomes of different assessment procedures based on effect sizes. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: This study was aimed to determine the impact of bioregenerative operations in case of degenerative cartilage lesions within the media knee compartment., Material and Methods: The CartilageRegistry DGOU was founded in 2013. At the deadline August 2016 a total of 1847 patients were included. A total of 23.3% (n = 432) was suffering from a degenerative cartilage lesion in the medial compartment. Follow-up was performed after 6, 12, and 24 months (online evaluation). The patients were asked for their subject feeling as well as the KOOS (Knee injury and Osteoarthritis Outcome Score) was determined., Results: Most of the patients (n = 358) suffered from a single femoral lesion. In 25 cases single tibial and in 49 cases combined defects ("kissing lesions") were addressed by different treatment options: 39.9% autologous chondrocyte transplantation, in 8.1% in combination with a spongiosa plasty. Other treatments were drilling, microfracturing with or without matrix. In 17.9% the surgeons had chosen combined methods. The bioregenerative treatment was combined with a concomitant operation in 39.7% in patients with medial, in 56.0% in patients with a tibial, and in 67.9% in patients with combined defects. The mostly performed additional operations were osteotomies. There were no gender differences at baseline or during follow-up. The history of patients with femoral defects was shorter than in the other groups. The patients with medial defects judged the subjective outcome significant more frequently better after 6, 12, or 24 months compared with the other groups. The KOOS raised from baseline (median 52 points) to a median of 75 after 6, to 78 points after 12, and to 80 points after 24 months. Patients with femoral defects had a better KOOS-outcome in tendency. Revision operations were required in 7.1%., Conclusions: The treatment of degenerative cartilage lesions (respective early OA) by bioregenerative procedures are well-established measures. These treatments are sufficient to produce high patients' satisfaction and acceptable short/midterm results., Competing Interests: The authors declare that they have no conflict of interest./Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Autologous chondrocyte implantation (ACI) and microfracture are established treatments for large, full-thickness cartilage defects, but there is still a need to expand the clinical and health economic knowledge of these procedures., Purpose: To confirm the noninferiority of ACI compared with microfracture., Study Design: Randomized controlled trial; Level of evidence, 2., Methods: Patients were randomized to be treated with matrix-associated ACI using spheroid technology (n = 52) or microfracture (n = 50). Both procedures followed standard methods. Patients were assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS), MOCART (magnetic resonance observation of cartilage repair tissue) scoring system, Bern score, modified Lysholm score, International Cartilage Repair Society (ICRS) rating (histological and immunochemical scoring after rebiopsy 24 months after implantation), and International Knee Documentation Committee (IKDC) examination form. The main assessments were conducted 24 months after study treatment., Results: In the primary intention-to-treat analysis, the overall KOOS score for both ACI and microfracture yielded a statistically significant improvement relative to baseline. According to the between-group analysis, ACI passed the test of noninferiority compared with microfracture; thus, the primary goal of the study was achieved. The KOOS subscores yielded the same qualitative results as the overall KOOS score (ie, for each of these, noninferiority was demonstrated), and in 1 case (Activities of Daily Living subscore), the threshold for superiority was passed. The subgroup analyses did not yield any clear evidence of an association between treatment effect and any of the categories investigated (age, diagnosis, defect localization, sex). A histological analysis of biopsies from 16 patients (ACI: n = 9; microfracture: n = 7) suggested a better quality of repair in the patients treated with ACI., Conclusion: The efficacy of both ACI and microfracture was demonstrated with respect to both functional outcomes and morphological repair. The primary analysis confirmed the statistical hypothesis of the noninferiority of ACI, even for relatively small cartilage defects (1-4 cm 2 ) treated in this study, the indication for which microfracture is generally accepted as the standard of care. ACI showed significant superiority in the KOOS subscores of Activities of Daily Living at 24 months and Knee-related Quality of Life at 12 months., Registration: NCT01222559 (ClinicalTrials.gov identifier)., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: The present study was funded by CO.DON. P.N. has received consulting fees from CO.DON and has received educational support from Aesculap, Arthrex, Geistlich, Moximed, Stryker, and Medi. W.Z. has received consulting fees from CO.DON. S.F. has received consulting fees from Arthrex and Bauerfeind. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Case: A 10-year-old girl presented after possible occult hip trauma, with shortening of the leg being the initial clinical symptom, followed by motion-dependent pain. She had limited external rotation in extension with anterior apprehension. Radiographically, the deformity was an anterior tilt of the epiphysis with coxa vara. Surgery included surgical dislocation using a retinacular flap for the anterior open wedge femoral neck osteotomy for extension and posterior translation, with an excellent 4.5-year clinical outcome., Conclusions: Caput flexum is a rare deformity with localized premature closure of the anterior growth plate of the hip. To avoid secondary impingement, an osteotomy was successfully placed close to the deformity.

Background: Autologous chondrocyte implantation (ACI) is an established method for treating cartilage defects in the knee of adult patients. However, less is known about its effectiveness in adolescents., Hypothesis: Third-generation matrix-associated ACI (MACI) using spheroids (co.don chondrosphere/Spherox) is an effective and safe treatment for articular cartilage defects in adolescents aged 15 to 17 years, with outcomes comparable with those for young adults aged 18 to 34 years., Study Design: Cohort study; Level of evidence, 3., Methods: A total of 71 patients (29 adolescents, 42 young adults) who had undergone ACI using spheroids were evaluated retrospectively in this multicenter study. For adolescents, the mean defect size was 4.6 ± 2.4 cm 2 , and the follow-up range was 3.5 to 8.0 years (mean, 63.3 months). For young adults, the mean defect size was 4.7 ± 1.2 cm 2 , and the follow-up range was 3.8 to 4.3 years (mean, 48.4 months). At the follow-up assessment, outcomes were assessed by using validated questionnaires (Knee injury and Osteoarthritis Outcome Score [KOOS], International Knee Documentation Committee [IKDC] subjective knee evaluation form and current health assessment form, and modified Lysholm score), the magnetic resonance observation of cartilage repair tissue (MOCART) score, and if relevant, time to treatment failure. Safety was assessed by the treatment failure rate., Results: No significant difference between the 2 study groups was found for KOOS, IKDC, or MOCART scores, with all patients achieving high functional values. A significant difference was found in the modified Lysholm score, favoring the young adult group over the adolescent group (22.3 ± 1.9 vs 21.0 ± 2.4, respectively; P = .0123). There were no differences between the rates of treatment failure, with 3% in the adolescent group and 5% in the young adult group., Conclusion: Third-generation MACI using spheroids is a safe and effective treatment for large cartilage defects of the knee in adolescents at midterm follow-up. Outcomes are comparable with those for young adults after ACI., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was sponsored by co.don. A.H. is an employee of co.don. P.N. receives royalties for limited educational purposes from the European Union, AO Foundation, DePuy Synthes, TiGenix, and DKG and receives consulting fees from Arthrex and Stryker. S.F. is affiliated with Arthrex and Bauerfeind. K.R. has received royalties for medical leadership of this study. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Surgical principles for treatment of full-thickness cartilage defects of the knee include bone marrow stimulation techniques (i.e. arthroscopic microfracturing) and transplantation techniques (i.e. autologous chondrocyte implantation and osteochondral transplantation). On the basis of increasing scientific evidence, indications for these established therapeutical concepts have been specified and clear recommendations for practical use have been given. Within recent years, matrix-augmented bone marrow stimulation has been established as a new treatment concept for chondral lesions. To date, scientific evidence is limited and specific indications are still unclear. The present paper gives an overview of available products as well as preclinical and clinical scientific evidence. On the basis of the present evidence and an expert consensus from the "Working Group on Tissue Regeneration" of the German Orthopaedic and Trauma Society (DGOU), indications are specified and recommendations for the use of matrix-augmented bone marrow stimulation are given. In principle, it can be stated that the various products offered in this field differ considerably in terms of the number and quality of related studies (evidence level). Against the background of the current data situation, their application is currently seen in the border area between cell transplantation and bone marrow stimulation techniques, but also as an improvement on traditional bone marrow stimulation within the indication range of microfracturing. The recommendations of the Working Group have preliminary character and require re-evaluation after improvement of the study situation., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)