Follow-up Treatment after Cartilage Therapy of the Knee Joint - a Recommendation of the DGOU Clinical Tissue Regeneration Working Group. / Nachbehandlung nach Knorpeltherapie am Kniegelenk ­ eine Empfehlung der AG Klinische Geweberegeneration der DGOU.

The first follow-up treatment recommendation from the DGOU's Clinical Tissue Regeneration working group dates back to 2012. New scientific evidence and changed framework conditions made it necessary to update the follow-up treatment recommendations after cartilage therapy.As part of a multi-stage member survey, a consensus was reached which, together with the scientific evidence, provides the basis for the present follow-up treatment recommendation.The decisive criterion for follow-up treatment is still the defect localisation. A distinction is made between femorotibial and patellofemoral defects. In addition, further criteria regarding cartilage defects are now also taken into account (stable cartilage edge, location outside the main stress zone) and the different methods of cartilage therapy (e. g. osteochondral transplantation, minced cartilage) are discussed.The present updated recommendation includes different aspects of follow-up treatment, starting with early perioperative management through to sports clearance and resumption of contact sports after cartilage therapy has taken place.

Etiology, Classification, Diagnostics, and Conservative Management of Osteochondral Lesions of the Talus. 2023 Recommendations of the Working Group "Clinical Tissue Regeneration" of the German Society of Orthopedics and Traumatology.

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.

[Sports injuries : What type of imaging is required?] / Sportverletzungen : Welche Bildgebung ist erforderlich?

BACKGROUND: Imaging is of great importance in sports injuries, since the indication for conservative and surgical therapy depends on precise knowledge of the extent of the damage. OBJECTIVES: Typical sports injuries and their imaging requirements are to be presented as examples. CONCLUSIONS: In order to detect the often subtle pathologies, imaging must be adapted to the clinical diagnosis that is specifically suspected.

The Effect of Smoking on the Outcome of Matrix-Based Autologous Chondrocyte Implantation: Data from the German Cartilage Registry.

Smoking is known to have various deleterious effects on health. However, it is not clear whether smoking negatively affects the postoperative outcome following matrix-based autologous cartilage implantation (MACI) in the knee. The purpose of this study was to evaluate the effect of smoking on the outcome of MACI in the knee. A total of 281 patients receiving MACI in the knee between 2015 and 2018 were registered in the German Cartilage Database. The cohort was divided into ex-smokers, smokers, and nonsmokers. Data regarding the Knee Injury and Osteoarthritis Outcome Score (KOOS), the numeric rating scale (NRS) for pain, and satisfaction with the outcome were analyzed and compared. Follow-ups were performed at 6, 12, and 24 months after surgery. Of the 281 patients, 225 (80.1%) were nonsmokers, 43 (15.3%) were smokers, and 13 (4.6%) were ex-smokers. The three groups were comparable with respect to age, sex, body mass index (BMI), height, defect size, the need for additional reconstruction of the subchondral bone defect, number of previous knee surgeries, and defect location. However, nonsmokers had a significantly lower weight as compared with smokers. Besides a significantly lower preoperative NRS of nonsmokers as compared with smokers, there were no significant differences between the three groups with respect to KOOS, NRS, and satisfaction at 6, 12, and 24 months of follow-ups. The present study of data retrieved from the German Cartilage Registry suggests that the smoking status does not influence the outcome of MACI in the knee.

Germany has a high demand in meniscal allograft transplantation but is subject to health economic and legal challenges: a survey of the German Knee Society.

PURPOSE: To determine the current status and demand of meniscal allograft transplantation (MAT) in Germany among members of the German Knee Society (= Deutsche Kniegesellschaft; DKG). METHODS: An online survey was conducted between May 2021 and June 2021 and sent to all members of the DKG. The survey questionnaire consisted of 19 questions to determine the demand and technical aspects of MAT among the participants and to identify areas of improvement in MAT in Germany. RESULTS: Overall, 152 participants, 136 (89.5%) from Germany, 8 (5.3%) from Switzerland, 6 (4.0%) from Austria, and 2 (1.3%) from other countries completed the online survey, with the majority working in non-academic institutions. According to the regulations of the DKG, 87 (57.2%) participants were board certified as specialized knee surgeons and 97 (63.8%) worked primarily in the field of orthopedic sports medicine. MAT was considered clinically necessary in Germany by 139 (91.5%) participants. Patient age (83.6%), post-meniscectomy syndrome in isolated lateral (79.6%) and medial (71.7%) meniscus deficiency, and functional and athletic demands (43.4%) were the most important determinants to consider MAT in patients. Participants reported that reimbursement (82.9%), jurisdiction over the use of donor grafts (77.6%), and the availability of meniscal allografts (76.3%) are the main challenges in performing MAT in Germany. The most frequently used meniscal allograft types by 54 (35.5%) participants who had already performed MAT were fresh-frozen grafts (56.6%), peracetic acid-ethanol sterilized grafts (35.9%), and cryopreserved grafts (7.6%). Participants reported to perform suture-only fixation more often than bone block fixation for both medial (73.6% vs. 22.6%) and lateral (69.8% vs. 24.5%) MAT. CONCLUSION: More than 90% of the responding members of the DKG indicated that MAT is a clinically important and valuable procedure in Germany. Reimbursement, jurisdiction over the use of donor grafts, and the availability of meniscal allografts should be improved. This survey is intended to support future efforts to facilitate MAT in daily clinical practice in Germany. LEVEL OF EVIDENCE: Level V.

Magnetic resonance observation of cartilage repair tissue (MOCART) 2.0 for the evaluation of retropatellar autologous chondrocyte transplantation and correlation to clinical outcome.

BACKGROUND: Matrix-associated chondrocyte transplantation (MACT) has become an established treatment option for cartilage defects. OBJECTIVE: Three objectives were defined: first, to evaluate retropatellar cartilage grafts using Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score; second, to determine whether clinical outcome correlates with specific parameters or overall results; third, to screen those parameters for their ability to predict a clinical outcome of Delta IKDC ≥ 20 as a threshold for good clinical response at 12 months. METHODS: 38 patients were included of whom all underwent retropatellar MACT. MRI was performed 3, 6 and 12 months postoperatively. The clinical status was determined using International Knee Documentation Committee Subjective Form (IKDC). Correlations of MOCART 2.0 parameters and Delta IKDC scores were quantified by nonparametric Spearman's R. Those parameters with significant correlations (p < 0.05) were screened for their ability to predict a clinical outcome of Delta IKDC ≥ 20 at 12 months. RESULTS: Significant correlations were identified for the parameters MOCART total 6 months (p < 0.05), Surface 6 months (p < 0.05), Surface 12 months (p < 0.05), Structure 6 months (p < 0.01), Structure 12 months (p < 0.05), Subchondral changes 3 months (p < 0.0001), Subchondral changes 6 months (p < 0.05) and Subchondral changes 12 months (p < 0.05). Among all MRI score parameters, Subchondral changes 3 months achieved the highest accuracy of 0.76 (0.62-0.86) in predicting Delta IKDC ≥ 20 after 12 months. CONCLUSION: Some of the MOCART 2.0 parameters show significant correlation with Delta IKDC scores in the postoperative course after retropatellar MACT, which seems to depend on the time interval between surgery and MRI acquisition.

Editorial Commentary: Bone Marrow Lesion as a Prognostic Factor for Osteochondral Allograft Transplantation of Cartilage Defects in the Knee Joint.

Bone marrow lesions (BML) can be categorized as ischemic, mechanical, or reactive. BML are associated with cartilage loss and can be interpreted as a "stress-related bone marrow edema," and are a consequence of subchondral overload due to lack of cartilaginous cushioning and load distribution. The prevalence, depth, and cross-sectional area of BML increase with the degree cartilage defect. There is a risk that bone marrow edema will progress to subchondral cysts, and cysts are a point of no return of a BML. Thus, successful treatment of cartilage damage requires causally addressing the bone marrow edema, and it is also crucial for the therapy of the BML that cartilage damage is completely treated. A postoperative BML is associated with incomplete defect coverage due to incomplete ingrowth of the osteochondral allograft with missing closure of the cartilage surface, or insufficient containment. Ideal treatment for a circumscribed subchondral BML is a single cylinder replacing the damaged cartilage and the entire BML with an osteochondral allograft. In the case of larger defects or larger BML, successful treatment of the cartilage defect is the critical point.

Effect of the defect localization and size on the success of third-generation autologous chondrocyte implantation in the knee joint.

INTRODUCTION: Femoral and patellar cartilage defects with a defect size > 2.5 cm2 are a potential indication for an autologous chondrocyte implantation (ACI). However, the influence of the localization and the absolute and relative defect size on the clinical outcome has not yet been determined. The purpose of this study is to analyze the influence of the localization and the absolute and relative defect size on the clinical outcome after third-generation autologous chondrocyte implantation. METHODS: A total of 50 patients with cartilage defects of the knee were treated with third-generation autologous chondrocyte implantation (Novocart® 3D). A match paired analysis was performed of 25 treated femoral and 25 treated patella defects with a follow-up of three years. MRI data was used to do the manual segmentation of the cartilage layer throughout the knee joint. The defect size was determined by taking the defect size measured in the MRI in relation to the whole cartilage area. The clinical outcome was measured by the IKDC score and VAS pre-operatively and after six, 12, 24, and 36 months post-operatively. RESULTS: IKDC and VAS scores showed a significant improvement from the baseline in both groups. Femoral cartilage defects showed significantly superior clinical results in the analyzed scores compared to patellar defects. The femoral group improved IKDC from 33.9 (SD 18.1) pre-operatively to 71.5 (SD 17.4) after three years and the VAS from 6.9 (SD 2.9) pre-operatively to 2.4 (SD 2.5) after three years. In the patellar group, IKDC improved from 36.1 (SD 12.6) pre-operatively to 54.7 (SD 20.3) after three years and the VAS improved from 6.7 (SD 2.8) pre-operatively to 3.4 (SD 2.) after three years. Regarding the defect size, results showed that the same absolute defect size at med FC (4.8, range 2-15) and patella (4.6, range 2-12) has a significantly different share of the total cartilaginous size of the joint compartment (med FC: 6.7, range 1.2-13.9; pat: 18.9, range 4.0-47.0). However, there was no significant influence of the relative defect size on the clinical outcome in either patellar or femoral localization. CONCLUSION: Third-generation autologous chondrocyte implantation in ACI-treated femoral cartilage defects leads to a superior clinical outcome in a follow-up of three years compared with patellar defects. No significant influence of the defect size was found in either femoral or patellar cartilage defects.

Temporal TGF-ß Supergene Family Signalling Cues Modulating Tissue Morphogenesis: Chondrogenesis within a Muscle Tissue Model?

Temporal translational signalling cues modulate all forms of tissue morphogenesis. However, if the rules to obtain specific tissues rely upon specific ligands to be active or inactive, does this mean we can engineer any tissue from another? The present study focused on the temporal effect of "multiple" morphogen interactions on muscle tissue to figure out if chondrogenesis could be induced, opening up the way for new tissue models or therapies. Gene expression and histomorphometrical analysis of muscle tissue exposed to rat bone morphogenic protein 2 (rBMP-2), rat transforming growth factor beta 3 (rTGF-ß3), and/or rBMP-7, including different combinations applied briefly for 48 h or continuously for 30 days, revealed that a continuous rBMP-2 stimulation seems to be critical to initiate a chondrogenesis response that was limited to the first seven days of culture, but only in the absence of rBMP-7 and/or rTGF-ß3. After day 7, unknown modulatory effects retard rBMP-2s' effect where only through the paired-up addition of rBMP-7 and/or rTGF-ß3 a chondrogenesis-like reaction seemed to be maintained. This new tissue model, whilst still very crude in its design, is a world-first attempt to better understand how multiple morphogens affect tissue morphogenesis with time, with our goal being to one day predict the chronological order of what signals have to be applied, when, for how long, and with which other signals to induce and maintain a desired tissue morphogenesis.

Patient-Reported and Magnetic Resonance Imaging Outcomes of Third-Generation Autologous Chondrocyte Implantation After 10 Years.

PURPOSE: To evaluate the long-term clinical and radiologic outcomes of third-generation autologous chondrocyte implantation (ACI) for the treatment of focal cartilage defects of the knee. METHODS: Data capture was carried out between 2004 and 2018. Included were patients with cartilage defects of the knee joint with an International Cartilage Repair Society grade of III or higher treated with third-generation ACI who had a minimum follow-up period of 10 years. International Knee Documentation Committee scores and assessment of pain at rest and on movement using visual analog scale scores were captured preoperatively and at 6 months postoperatively, as well as annually thereafter. In addition, we performed magnetic resonance imaging examinations in 13 cases after 10 years. The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score was used to evaluate the ACI cartilage. RESULTS: A total of 54 patients met the inclusion criteria. Of these, 30 reached the 10-year follow-up point and were included in this assessment. At 10 years postoperatively, all clinical outcome parameters showed a statistically significant improvement compared with the preoperative situation, with a responder rate of 70%. The average MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score after 10 years was 59.2 points (range, 20-100 points), and over 60% of the evaluated patients showed good integration of the implant at 10 years postoperatively. CONCLUSIONS: The clinical and radiologic findings of this study show that third-generation ACI is a suitable and effective option in the treatment of full-thickness cartilage defects of the knee. At 10 years after surgery, third-generation ACI shows stable results and leads to significant improvement in all clinical outcome parameters. Despite these results, revision surgery after third-generation ACI is common and was needed in 23% of patients in this study. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Rotator Cuff Repair With Autologous Tenocytes and Biodegradable Collagen Scaffold: A Histological and Biomechanical Study in Sheep.

BACKGROUND: Large rotator cuff tears still represent a challenging problem in orthopaedics. The use of tenocytes on biomaterials/scaffolds for the repair of large rotator cuff defects might be a promising approach in the field of tendon regeneration. HYPOTHESIS: Cultivated autologous tenocytes seeded on a collagen scaffold lead to enhanced histological and biomechanical results after rotator cuff repair in a sheep model as compared with unseeded scaffolds in an acute setting. STUDY DESIGN: Controlled laboratory study. METHODS: At the tendon-bone junction of the infraspinatus tendon of the right foreleg of 24 sheep, a 3.5 × 1.5-cm tendon defect was created. Sheep were randomly allocated to group 1, a defect; group 2, where an unseeded collagen scaffold was implanted; or group 3, which received the implantation of a collagen scaffold seeded with autologous tenocytes. Twelve weeks postoperatively, tendon regeneration was examined histologically and biomechanically. RESULTS: The histology of the neotendons of group 3 showed better fiber patterns, a higher production of proteoglycans, and an increased genesis of collagen III in contrast to groups 1 and 2. Immunostaining revealed less tissue dedifferentiation, a more structured cartilage layer, and homogeneous cartilage-bone transition in group 3 in comparison with groups 1 and 2. Biomechanically, the tensile strength of the reconstructed tendons in group 3 (mean load to failure, 2516 N; SD, 407.5 N) was approximately 84% that of the native tendons (mean load to failure, 2995 N; SD, 223.1 N) without statistical significance. A significant difference (P = .0095) was registered between group 1 (66.9% with a mean load to failure of 2004 N; SD, 273.8 N) and the native tendons, as well as between group 2 (69.7% with a mean load to failure of 2088 N; SD, 675.4 N) and the native tendons for mean ultimate tensile strength. In breaking stress, a significant difference (P = .0095) was seen between group 1 (mean breaking stress, 1335 N/mm2; SD, 182.7 N/mm2) and the native tendons, as well as between group 2 (breaking stress, 1392 N/mm2; SD, 450.2 N/mm2) and the native tendons (mean breaking stress, 1996 N/mm2; SD, 148.7 N/mm2). Again, there was no significant difference between group 3 (mean breaking stress, 1677 N/mm2; SD, 271.7 N/mm2) and the native tendons. CONCLUSION: Autologous tenocytes seeded on collagen scaffolds yield enhanced biomechanical results after tendon-bone reconstruction as compared with unseeded scaffolds in an acute setting. Biomechanical results and histological outcomes were promising, showing that the use of autologous tenocytes with specific carrier matrices could be a novel approach for repairing rotator cuff tears. CLINICAL RELEVANCE: This study supports the use of tenocytes and scaffolds for improving the quality of tendon-bone regeneration.

Graft Hypertrophy After Third-Generation Autologous Chondrocyte Implantation Has No Correlation With Reduced Cartilage Quality: Matched-Pair Analysis Using T2-Weighted Mapping.

BACKGROUND: Graft hypertrophy is common after matrix-based autologous chondrocyte implantation (ACI) in the knee joint. However, it is not clear whether graft hypertrophy is a complication or an adjustment reaction in the cartilage regeneration after ACI. PURPOSE: To analyze the cartilage quality of the ACI regeneration with graft hypertrophy using T2-weighted mapping. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 91 patients with isolated cartilage defects (International Cartilage Repair Society [ICRS] grade III-IV) of the knee were treated with Novocart 3D, a third-generation, matrix-based, ACI procedure in the knee joint. All patients were evaluated with a standardized magnetic resonance imaging protocol after 3, 6, 12, 24, 36, and 48 months postoperatively. For morphological and biochemical assessment, the T2-weighted relaxation times of the ACI grafts as well as the healthy surrounding cartilage were determined. The results of the 20 patients with graft hypertrophy (hypertrophic group) were compared with the results of 21 matched patients without graft hypertrophy (nonhypertrophic group) after ACI. Match-paired analysis was performed by comparison of age, defect size, and body mass index. RESULTS: The T2-weighted relaxation times of the ACI graft showed significant improvement, with values decreasing from 52.1 milliseconds to 33.3 milliseconds after 48 months. After 12 months, the T2-weighted relaxation times were constant and comparable with the healthy surrounding cartilage. Graft hypertrophy was seen in 22% (n = 20) of the patients who underwent ACI. A significant difference in T2-weighted relaxation times between the hypertrophic and nonhypertrophic ACI grafts could not be found except after 36 months (hypertrophic T2-weighted relaxation time/nonhypertrophic T2-weighted relaxation time: 3 months, 48.0/56.4 ms, P = .666; 6 months, 45.6/42.5 ms, P = .280; 12 months, 39.3/34.7 ms, P = .850; 24 months, 34.8/32.2 ms, P = .742; 36 months, 34.6/38.2 ms, P = .030; 48 months, 34.2/32.3 ms, P = .693). CONCLUSION: The T2-weighted relaxation time of the ACI graft cartilage showed significant improvements over the observation period of 4 years postoperatively. After 2 years, graft maturation was completed. Graft hypertrophy after ACI was seen in 22% of the patients. Reduced cartilage quality could not be found in patients with graft hypertrophy after ACI.

Can Salter osteotomy correct late diagnosed hip dysplasia: A retrospective evaluation of 49 hips after 6.7 years?

BACKGROUND: Surgical treatment of late diagnosed development dysplasia of the hip (DDH) remains challenging with several methods being described. We therefore retrospectively evaluated the outcome of Salter innominate osteotomy (SIO) in patients with fully-grown bone, to evaluate whether this surgical procedure allows sufficient acetabular correction. MATERIAL AND METHODS: Between 2004-2012 SIO had been performed in 45 patients (49 hips) with late diagnosed DDH. The evaluation included pre- and postoperative radiographs (n=49), the complication rate (n=49) and the clinical outcome (WOMAC, HHS, UCLA) (n=34). RESULTS: Mean age at surgery was 27.6 (16-51) with a follow-up of 6.7±2.7 (0.9-11.0) years. Radiologically, a good acetabular correction with a significant improvement of the Center Edge angle (15.4° to 34.9°), sharps angle (45.7° to 32.0°) and migration percentage (33.2% to 14.4%) (p<0.001) was found. Clinical results revealed a WOMAC of 13.9±13.3, UCLA of 7.8±2.1 and HHS of 85.0±11.8. Complications were noted for 10 patients (20%) with 7 (14%) requiring revision. CONCLUSION: The results demonstrated that SIO achieved a satisfying acetabular correction and good clinical results in late diagnosed DDH. It therefore might be an option in some cases, although periacetabular osteotomy techniques are currently preferable used as they allow a wider range of acetabular correction. LEVEL OF EVIDENCE: IV, retrospective observational study.

The influence of different footprint preparation techniques on tissue regeneration in rotator cuff repair in an animal model.

INTRODUCTION: Rotator cuff tears are common diseases of the upper extremity. There are no recommendations to the surgeon on how to prepare the footprint to ensure optimal tendon-to-bone healing. However, biologic augmentation using stem cells and growth factors is considered to encourage the healing process of the tendon. The aim of the study was to investigate the biomechanical and histological outcome of different footprint preparations in rotator cuff repair. MATERIAL AND METHODS: One hundred and eighty-nine Sprague-Dawley rats were randomly assigned to either spongialization, radiofrequency ablation or an untreated control group. Rats were killed after 1 or 7 weeks for histological evaluation or after 7 weeks for biomechanical testing. RESULTS: Histological evaluation showed better tissue organization in the control and spongialization group compared to the radiofrequency ablation group. The highest collagen I to collagen III quotient was found in the control group, followed closely by the spongialization group. Measured quotients showed a decrease in the values after 1 week compared to the values after 7 weeks, except in the radiofrequency ablation group, where an increase was detected. A significant difference was found in the load to failure test comparing the radiofrequency ablation group to the spongialization group (p = 0.0409) and control group (p = 0.014), but not comparing the spongialization group to the control group (p = 0.2456). CONCLUSIONS: The results of this study suggest that spongialization of the footprint before attaching the torn supraspinatus tendon can lead to better structural properties and higher quality of tendon-to-bone restoration at the insertion area when compared with radiofrequency ablation.

Cell Toxicity in Fibroblasts, Tenocytes, and Human Mesenchymal Stem Cells-A Comparison of Necrosis and Apoptosis-Inducing Ability in Ropivacaine, Bupivacaine, and Triamcinolone.

PURPOSE: To analyze the ability of ropivacaine, bupivacaine, and triamcinolone to induce apoptosis and necrosis in fibroblasts, tenocytes, and human mesenchymal stem cells. METHODS: Human dermal fibroblasts, adipose-derived human mesenchymal stem cells (hMSCs), and tenocytes gained from the rotator cuff tendon were seeded with a cell density of 0.5 × 104/cm2. One specimen of ropivacaine, bupivacaine, and triamcinolone was tested separately on the cells with separate concentrations of 0.5%, 0.25%, and 0.125% for each specimen. The negative control received no agent, only a change of medium. The incubation period for each agent was 30 minutes. After a change of medium and 1 hour, 24 hours, and 7 days of incubation, 104 cells were harvested and analyzed via fluorescence-activated cell sorting with double-staining with annexin V and propidium iodide. Statistical analysis to determine significant difference (P < .05) between the groups with SPSS statistics 23 through one-way analysis of variance with a univariate general linear model was performed. RESULTS: Bupivacaine showed necrosis-inducing effects on fibroblasts and tenocytes, with the necrotic effect peaking at 0.5% and 0.25%. Ropivacaine and triamcinolone caused no significant necrosis. Compared with fibroblasts and tenocytes, hMSCs did not show significant necrotic or apoptotic effects after exposure to bupivacaine. Overall, no significant differences in apoptosis were detected between different cell lines, varying concentrations, or time measurements. CONCLUSIONS: Bupivacaine 0.5% and 0.25% have the most necrosis-inducing effects on fibroblasts and tenocytes. Ropivacaine caused less necrosis than bupivaine. Compared with fibroblasts and tenocytes, hMSCs were not affected by necrosis using any of the tested agents. A significant apoptosis-inducing effect could not be detected for the different cell lines. CLINICAL RELEVANCE: Possible cell toxicity raises questions of concern for intra-articular injections using local anesthetics and corticosteroids. The present study demonstrates the necrotic and apoptotic effects of ropivacaine, bupivacaine, and triamcinolone and may give recommendations for intra-articular use of local anesthetics and corticosteroids.

Incomplete defect filling after third generation autologous chondrocyte implantation.

INTRODUCTION: Third generation autologous chondrocyte implantation (ACI) is a suitable method for the treatment of cartilage defects in the knee joint. However, knowledge about the development of graft thickness and the clinical relevance of incomplete defect filling in the postoperative course is low. This prospective study analyses the graft integration into the surrounding cartilage, with special consideration of the graft thickness. MATERIAL AND METHODS: A total of 71 consecutive patients with 79 cartilage defects were treated with third generation autologous chondrocyte implantation (NOVOCART 3D) in the knee. Follow-up magnetic resonance imaging (MRI) was performed at 0.25, 0.5, 1 and 2 years. Graft thickness was measured compared to the surrounding healthy cartilage. The International Knee Documentation Committee (IKDC) scoring system and the visual analogue scale (VAS) were used for clinical evaluation. Cartilage defect filling was classified as the percentage of the surrounding cartilage. RESULTS: The average graft thickness showed a significant increase between 3 and 6 months after autologous chondrocyte implantation. Incomplete defect filling occurred in 44 (55.7%) cases. Of these, 33 cases showed incomplete defect filling grade I (> 75%), 10 cases were grade II (> 50%) and one case grade III (> 25%). Incomplete defect filling grade IV (< 25%) was not observed. Incomplete defect filling occurred significantly more often in women (p = 0.021), without worse clinical results. CONCLUSIONS: Graft thickness after third generation autologous chondrocyte implantation shows increasing graft thickness over the period of 2 years postoperatively. A high rate of incomplete defect filling in the surrounding cartilage was observed, without worse clinical results.

Analysis of the autologous chondrocyte quality of matrix-based autologous chondrocyte implantation in the knee joint.

PURPOSE: Matrix based autologous chondrocyte implantation is an established method for treatment of full cartilage defects in the knee joint, but little is known about the influence of the implanted autologous chondrocyte quality and its clinical value. The aim of this study is to evaluate the influence of the gene expression of the implanted autologous chondrocytes on the clinical outcomes in the follow-up period of three years. METHODS: Biological parameters of the implanted chondrocytes were analysed histologically and immunohistologically. An analysis of the gene expression of the relevant chondrogenic dedifferentiation markers was performed as well. In order to detect the rate of apoptosis, we analysed specific apoptosis markers. To evaluate the clinical outcome, the International Knee Documentation Committee (IKDC) subjective score and the visual analogue scale (VAS) were used pre-operatively and after 0.5, one, two and three years. RESULTS: Significantly improved clinical scores were observed. The subjective IKDC score increased from 50.6 ± 20.7 points to 69.3 ± 26.1 points at three years (p = 0.001). The implanted chondrocytes showed a typical expression of the chondrogenic markers with a high rate of collagen type II expression without dedifferentiation. The analysed differentiation, dedifferentiation and apoptosis markers showed no influence on the clinical outcome. CONCLUSIONS: The implanted autologous chondrocytes have a high chondrogenic quality with a high rate of collagen type II expression without dedifferentiation. An influence of differentiation, de-differentiation and apoptosis marker gene expression on the clinical outcomes could not be found in a follow-up period of three years. LEVEL OF EVIDENCE: Case series; Level of evidence, 3.

Revision surgery after third generation autologous chondrocyte implantation in the knee.

PURPOSE: Third generation autologous chondrocyte implantation (ACI) is an established treatment for full thickness cartilage defects in the knee joint. However, little is known about cases when revision surgery is needed. The aim of the present study is to investigate the complication rates and the main reasons for revision surgery after third generation autologous chondrocyte implantation in the knee joint. It is of particular interest to examine in which cases revision surgery is needed and in which cases a "wait and see" strategy should be used. METHODS: A total of 143 consecutive patients with 171 cartilage defects were included in this study with a minimum follow-up of two years. All defects were treated with third generation ACI (NOVACART®3D). Clinical evaluation was carried out after six months, followed by an annual evaluation using the International Knee Documentation Committee (IKDC) subjective score and the visual analogue scale (VAS) for rest and during activity. Revision surgery was documented. RESULTS: The revision rate was 23.4 % (n = 36). The following major reasons for revision surgery were found in our study: symptomatic bone marrow edema (8.3 %, n = 3), arthrofibrosis (22.2 %, n = 8) and partial graft cartilage deficiency (47.2 %, n = 17). The following revision surgery was performed: retrograde drilling combined with Iloprost infusion therapy for bone marrow oedema (8.4 %, n = 3), arthroscopic arthrolysis of the suprapatellar recess (22.2 %, n = 8) and microfracturing/antegrade drilling (47.3 %, n = 17). Significant improvements of clinical scores after revision surgery were observed. CONCLUSION: Revision surgery after third generation autologous chondrocyte implantation is common and is needed primarily in cases with arthrofibrosis, partial graft cartilage deficiency and symptomatic bone marrow oedema resulting in a significantly better clinical outcome.

Bone Marrow Edema in the Knee and Its Influence on Clinical Outcome After Matrix-Based Autologous Chondrocyte Implantation: Results After 3-Year Follow-up.

BACKGROUND: Third-generation autologous chondrocyte implantation (ACI) is an established method for treatment of full-thickness cartilage defects in the knee joint. Subchondral bone marrow edema (BME) is frequently observed after ACI, with unknown pathogenesis and clinical relevance. PURPOSE: To investigate the occurrence and clinical relevance of BME after third-generation ACI in the knee joint during the postoperative course of 36 months. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 38 circumscribed full-thickness cartilage defects in 30 patients were included in this study. All defects were treated with third-generation ACI (Novocart 3D). A standardized MRI examination was carried out after 1.5, 3, 6, 12, 24, and 36 months. Bone marrow edema was observed in 78.9% of defects over the postoperative course, with initial occurrence in the first 12 months. The size of the BMEs were determined according to their maximum diameter and were classified as small (<1 cm), medium (<2 cm), large (<4 cm), and very large (diffuse; >4 cm). Clinical outcomes in patients were analyzed by use of the International Knee Documentation Committee (IKDC) scoring system and a visual analog scale for pain. RESULTS: There were 5.3% (n=2) small, 28.9% (n=11) medium, 34.2% (n=13) large, and 10.5% (n=4) very large BMEs. In a subgroup analysis, cartilage defects of the medial femoral condyle showed significantly higher frequency of BME than did patellar defects. Clinical scores showed significant improvements throughout the entire study course (P<.05). Clinical patient outcome did not correlate with presence of BME at any time period (P>.05). CONCLUSION: Midterm clinical results of the matrix-based third-generation ACI showed a substantial amount of BME over a 36-month follow-up, but this did not correlate with worse clinical outcome. Patients with femoral cartilage defects were more often affected than were those with patellar cartilage defects.