Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelschäden am Kniegelenk. / Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelschäden am Kniegelenk.

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 cm2 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 cm2. 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.

Impact of compression stockings on leg swelling after arthroscopy - a prospective randomised pilot study.

BACKGROUND: Post-operative limb swelling may negatively affect the outcome of arthroscopic surgery and prolong rehabilitation. The aim of this pilot study was to evaluate the effect of compression stockings versus no compression on post-operative swelling and pain in the early post-operative phase. METHODS: A single-centre, randomised controlled trial was performed. Patients who underwent minor knee arthroscopy were randomised to wear class II compression stockings (23-32 mmHg) (CS) or no compression stockings (NCS) immediately post-operatively for ten days. All patients received low molecular weight heparin (LMWH) at prophylactic dosage. The primary outcome variable was post-operative swelling of the limb, quantified by using an optical 3D measurement system (Bodytronic© 600). Pain was rated on a visual analogue scale (VAS). From a total of 76 patients assessed, 19 patients were eligible for final analysis. The trial followed the CONSORT criteria, was registered at clinicaltrial.gov and approved by the local ethics committee. RESULTS: The circumference at the middle thigh (cF) was significantly different between groups at day 10 (p = 0.032; circumference - 1.35 ± 2.15% (CS) and + 0.79 ± 3.71% (NCS)). Significant differences were also noted around the knee (cD) at day 10 (p = 0.026) and a significant trend at cD and at the mid lower leg (cB1) at day 4. The volume of the thigh was also different with marked difference between days 1 and 4 between the two groups (p = 0.021; volume + 0.54 ± 2.03% (CS) and + 4.17 ± 4.67 (NCS)). Pain was lower in compression group (not statistically significant). CONCLUSIONS: Post-operative limb swelling can be reduced significantly by wearing compression stockings in the early post-operative phase when compared to not wearing stockings. This may improve the rehabilitation process after arthroscopic surgery. The optimal duration of compression therapy seems to be between three and ten days. TRIAL REGISTRATION: clinicaltrials.gov ( NCT02096562 , date of registration 11.11.2013).

Long-Term Clinical and MRI Results of Matrix-Assisted Autologous Chondrocyte Implantation for Articular Cartilage Defects of the Knee.

OBJECTIVE: To evaluate the long-term clinical and radiological outcome of matrix-assisted autologous chondrocyte implantation (mACI) for articular cartilage defects in the knee joint. DESIGN: Clinical evaluation was assessed in 21 patients with full-thickness cartilage defects, International Cartilage Repair Society (ICRS) grade IV. Clinical scoring was performed preoperatively and 12 years after transplantation using the International Knee Documentation Committee (IKDC) score, the Lysholm score, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Noyes sports activity rating scale. Morphologic evaluation of the repair tissue was assessed by magnetic resonance imaging (MRI) in 14 patients using the Kreuz-Henderson score. RESULTS: Clinical evaluation revealed significant improvement in the IKDC, the Lysholm, the KOOS, and the Noyes score. Morphological evaluation by MRI showed moderate to complete defect filling in 10 of 14 patients, demonstrating normal to nearly normal values in mean 74.29% of all assessed parameters. Significant correlation of the parameter cartilage signal and clinical outcome was found with the IKDC, Lysholm, and KOOS subscales ADL (activities of daily living) and QoL (quality of life). CONCLUSIONS: The clinical and radiological outcomes 12 years after transplantation suggest the confirmation of the promising results of the mid-term follow-up. This study therefore provides first indications that the implantation of mACI might be a suitable option for long-term cartilage repair. Future controlled studies need to address the exact parameters influencing the long-term outcome of mACI.

[Significance of Matrix-augmented Bone Marrow Stimulation for Treatment of Cartilage Defects of the Knee: A Consensus Statement of the DGOU Working Group on Tissue Regeneration]. / Stellenwert der matrixaugmentierten Knochenmarkstimulation in der Behandlung von Knorpelschäden des Kniegelenks: Konsensusempfehlungen der AG Klinische Geweberegeneration der DGOU.

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.

[Debridement in Focal Cartilage Damage of the knee. Systematical review of the literature and recommendations of the working group "clinical tissue regeneration" of the German Society of Orthopaedics and Trauma (DGOU)]. / Stellenwert des Débridements bei der Behandlung fokaler (Grad II ­â€ŠIII) Knorpelschäden des Kniegelenks. Systematische Literaturübersicht und Empfehlungen der AG Geweberegeneration (DGOU).

BACKGROUND: In clinical practice, there is still no definite treatment algorithm for focal, partial thickness cartilage lesions (grade II - III). It is well-established that debridement (shaving/lavage) of large degenerative cartilage lesions is not recommended, but there is no such recommendation in the case of focal, partial thickness cartilage defects. MATERIALS AND METHODS: The scientific rationale of cartilage shaving and joint lavage was investigated and a systematic analysis was performed of the literature on the clinical effect of cartilage debridement. Furthermore, a consensus statement on this issue was developed by the working group on Clinical Tissue Regeneration of the German Society of Orthopaedics and Trauma (DGOU). RESULTS: The therapeutic approach is different for asymptomatic lesions with biomechanical stable residual cartilage tissue and clinically symptomatic defects with unstable fragments. The benefit of a joint lavage or surface smoothening of focal partial thickness has not been proved. Even more importantly, the mechanical or thermal resection of cartilage tissue even induces a zone of necrosis in adjacent cartilage, and thus leads to additional injury. Therefore, large scale smoothening (shaving) of clinically asymptomatic, fibrillated or irregular cartilage defects should not be performed. However, if there are clinical symptoms, resection of unstable and delaminated cartilage fragments may be reasonable, as it can reduce harmful shear tension in residual tissue. This can help to brake the progression of the damage and avoid formation of free bodies. CONCLUSION: The decision criteria for debridement of partial thickness focal cartilage lesions are multifactorial and include the clinical symptoms, the size and the degree of the defect, the stability of remaining cartilage, localisation of the defect, and individual patient-specific parameters. Debridement is not recommended for asymptomatic lesions, but may be reasonable for symptomatic cases with unstable tissue.

Single-dose local anesthetics exhibit a type-, dose-, and time-dependent chondrotoxic effect on chondrocytes and cartilage: a systematic review of the current literature.

PURPOSE: Many studies have shown that local anesthetics may impede chondrocyte metabolism. However, the influence of a single-dose local anesthetics is controversial. The aim of this metaanalysis was to review the literature for studies investigating the cytotoxic effects of single-dose local anesthetics on chondrocytes and cartilage. METHODS: A comprehensive literature search was performed using established search engines (Medline, Embase) to identify studies, investigating the influence of single-dose local anesthetics on cartilage. The systematic analysis included the influence on histology, cell viability, morphology, and matrix production depending upon dose, exposure time, and type of local anesthetics. RESULTS: Twelve studies with four different local anesthetics were included in this metaanalysis. Bupivacaine and lidocaine were found to be more chondrotoxic than mepivacaine and ropivacaine. The amount of dead cells increased in a substance-, dose-, and time-dependent process. Osteoarthritic cartilage seems to be more vulnerable compared to intact cartilage. The toxic effects occur first in the superficial cartilage layers and include damage to membrane integrity, mitochondrial DNA, and nuclear changes. There is no study that could show a significant chondrotoxic effect with low concentrations of bupivacaine (0.0625%), ropivacaine (0.1 and 0.2%), and mepivacaine (0.5%). CONCLUSIONS: The cytotoxicity of local anesthetics on chondrocytes is dependent on dose, time, and type of local anesthetics. Single-dose intra-articular administration of local anesthetics impede chondrocyte metabolism and should be performed only with low concentrations for selected diagnostic purposes and painful joints. The use of lidocaine should be avoided. LEVEL OF EVIDENCE: II.

Treatment of a Focal Articular Cartilage Defect of the Talus with Polymer-Based Autologous Chondrocyte Implantation: A 12-Year Follow-Up Period.

Autologous chondrocyte implantation (ACI) is a first-line treatment option for large articular cartilage defects. Although well-established for cartilage defects in the knee, studies of the long-term outcomes of matrix-assisted ACI to treat cartilage defects in the ankle are rare. In the present report, we describe for the first time the long-term clinical and radiologic results 12 years after polymer-based matrix-assisted ACI treat a full-thickness talar cartilage defect in a 25-year-old male patient. The clinical outcome was assessed using the visual analog scale and Freiburg ankle score, magnetic resonance imaging evaluation using the Henderson-Kreuz scoring system and T2 mapping. Clinical assessment revealed improved visual analog scale and Freiburg ankle scores. The radiologic analysis and T2 relaxation time values indicated the formation of hyaline-like repair tissue. Polymer-based autologous chondrocytes has been shown to be a safe and clinically effective long-term treatment of articular cartilage defects in the talus.

Patient-specific factors influencing the traction forces in hip arthroscopy.

INTRODUCTION: The application of traction in hip arthroscopy is associated with peri-operative complications. Within a therapeutic case series, patient-related factors correlating with high-traction forces during hip arthroscopy and occurring complications should be identified. MATERIALS AND METHODS: In 30 male and 38 female patients (mean age: 44.5 years), intra-operative traction forces were monitored continuously using a specialised measurement device. A multivariate analysis was employed to identify patient-related factors influencing the traction force. Peri-operative complications (follow-up: 12 weeks) were evaluated by performing a single-case analysis. RESULTS: The mean initial force prior to penetration of the capsule ("initial force") was 477 N (men: 517 N; women: 444 N), decreasing after capsulotomy by an average of 17 %. The male gender (p < 0.001), Kellgren and Lawrence radiographic stage (p = 0.037), low minimum joint-space width (p = 0.029) and high body height/weight (p = 0.003/0.037) correlated significantly with higher distraction forces. The patient age and type of anaesthesia (general versus spinal) were not relevant. Complications were observed in ten patients on the first post-operative day. In two of these patients a partial sensory deficit of the lateral cutaneous femoral nerve persisted after 12 weeks. All patients with complications required initial traction forces of >400 N. CONCLUSIONS: The study revealed several patient-specific risk factors correlating with high-traction forces during hip arthroscopy. With view to potential complications, these patient groups require special attention during surgical treatment as well as in future studies.

Platelet-Rich Plasma Preparation Types Show Impact on Chondrogenic Differentiation, Migration, and Proliferation of Human Subchondral Mesenchymal Progenitor Cells.

PURPOSE: To evaluate the chondrogenic potential of platelet concentrates on human subchondral mesenchymal progenitor cells (MPCs) as assessed by histomorphometric analysis of proteoglycans and type II collagen. Furthermore, the migratory and proliferative effect of platelet concentrates were assessed. METHODS: Platelet-rich plasma (PRP) was prepared using preparation kits (Autologous Conditioned Plasma [ACP] Kit [Arthrex, Naples, FL]; Regen ACR-C Kit [Regen Lab, Le Mont-Sur-Lausanne, Switzerland]; and Dr.PRP Kit [Rmedica, Seoul, Republic of Korea]) by apheresis (PRP-A) and by centrifugation (PRP-C). In contrast to clinical application, freeze-and-thaw cycles were subsequently performed to activate platelets and to prevent medium coagulation by residual fibrinogen in vitro. MPCs were harvested from the cortico-spongious bone of femoral heads. Chondrogenic differentiation of MPCs was induced in high-density pellet cultures and evaluated by histochemical staining of typical cartilage matrix components. Migration of MPCs was assessed using a chemotaxis assay, and proliferation activity was measured by DNA content. RESULTS: MPCs cultured in the presence of 5% ACP, Regen, or Dr.PRP formed fibrous tissue, whereas MPCs stimulated with 5% PRP-A or PRP-C developed compact and dense cartilaginous tissue rich in type II collagen and proteoglycans. All platelet concentrates significantly (ACP, P = .00041; Regen, P = .00029; Dr.PRP, P = .00051; PRP-A, P < .0001; and PRP-C, P < .0001) stimulated migration of MPCs. All platelet concentrates but one (Dr.PRP, P = .63) showed a proliferative effect on MPCs, as shown by significant increases (ACP, P = .027; Regen, P = .0029; PRP-A, P = .00021; and PRP-C, P = .00069) in DNA content. CONCLUSIONS: Platelet concentrates obtained by different preparation methods exhibit different potentials to stimulate chondrogenic differentiation, migration, and proliferation of MPCs. Platelet concentrates obtained by commercially available preparation kits failed to induce chondrogenic differentiation of MPCs, whereas highly standardized PRP preparations did induce such differentiation. These findings suggest differing outcomes with PRP treatment in stem cell-based cartilage repair. CLINICAL RELEVANCE: Our findings may help to explain the variability of results in studies examining the use of PRP clinically.

Importance of a distal centralizer in experimental malpositioning of cemented stems. A biomechanical study on human femora.

INTRODUCTION: Femoral centralizers in total hip arthroplasty (THA) are designed to improve the neutral implant position and ensure a homogeneous cement mantle without implant-bone impingement. To date there are no data about the cement mantle configuration and implant position after malinsertion, as seen in mini-open approaches or adipose patients with a limited view. The present biomechanical study was performed to investigate whether a distal centralizer may correct and optimize the position of a malinserted femoral stem. MATERIAL AND METHODS: Thirteen MS 30 stems with and without a distal centralizer each were implanted in paired fresh human femora. Malinsertion was performed using a 3D guiding device with 10° deviation to the femoral axis in the sagittal plane. The thickness of the cement mantle was measured on the anterior, posterior, medial and lateral side of the implanted stem at a distance of 1 cm each. For each side data were taken at 13 points. RESULTS: Digital evaluation of the cement mantle thickness revealed compareable values in frontal plane when a centralizer was used (p > 0.4). In contrast the cement mantle thicknesses without a centralizing device varied in the distal region between 3.38 mm and 5.09 mm (p ≤ 0.001) and in the central region between 3.52 mm and 4.19 mm (p ≤ 0.009). CONCLUSIONS: A distal centralizer allows a more uniform cement mantle and neutral alignment even with a malinsertion of the femoral stem. This could reduce the failure rate and early loosening in complex THA.

Significantly worse isokinetic hamstring-quadriceps ratio in patellofemoral compared to condylar defects 4 years after autologous chondrocyte implantation.

PURPOSE: Detailed biomechanical analysis including isokinetic muscle strength measurements after autologous chondrocyte implantation (ACI) are still rare, but might be of crucial importance for long-term outcomes. The present prospective study was performed to evaluate whether defect location had any influence on clinical and biomechanical outcomes 4 years after ACI. METHODS: Forty-four patients with full-thickness cartilage defects ICRS grade III B and C underwent ACI and were assigned to two groups, the femoral condyle group or the patellofemoral joint group. Clinical scores were gathered preoperatively and 6, 12 and 48 months after implantation using the International Knee Documentation Committee (IKDC) score and the International Cartilage Repair Society (ICRS) form. Isokinetic strength measurements were performed 48 months postoperatively comparing healthy and operated knee joint of each patient. RESULTS: Clinical scores (ICRS, IKDC) showed continuous significant (p < 0.05) improvement over the study period for both groups. Isokinetic muscle strength measurements showed significantly reduced maximum strength capacities for the operated knee joint compared to the healthy knee in both groups (p < 0.05). Hamstring-quadriceps ratios of the operated extremity revealed a significant change in physiological muscle balancing (ratios >1.0) based on significantly impaired extensor muscle strength in the patellofemoral joint group. CONCLUSION: All patients showed significant strength deficits on the operated extremity 4 years after ACI. Furthermore, the patellofemoral compartment in particular showed significantly worse hamstring-quadriceps ratios compared to condylar defects. Consequently, more efforts should be made to restore muscular strength especially of the quadriceps and the rehabilitation protocol should be adjusted accordingly. LEVEL OF EVIDENCE: II.

Practical execution of defect preparation prior to surgical cartilage intervention: results from a representative meeting survey among experts.

During a specialised orthopedic meeting held on 'the state of the art in cartilage defect repair', all previously fully-registered participants were requested to participate in an electronic survey by the use of a moderator-presented "Power Point Presentation-based" 9-item questionnaire. The aim of this survey was to assess indication, approach, and treatment execution of cartilage defect debridement prior to planned microfracture (MFX) or autologous chondrocyte implantation (ACI). All participants completed the questionnaire (n = 146) resulting in a return rate of 100 %. An uncertainty exists as to whether the removal of the calcifying layer prior to cartilage repair must be carried out or not. The same was true for the acceptability of subchondral bleeding prior to microfracturing and its handling prior to autologous chondrocyte implantation. There is a degree of unanimity among experts regarding the management of osteophytes and bone marrow edema. In a homogenous society collective of consultants that frequently deal with cartilage defective pathologies, there still remain a significant heterogeneity in selected topics of defect debridement.

Fibronectin stimulates migration and proliferation, but not chondrogenic differentiation of human subchondral progenitor cells.

AIMS: To evaluate the impact of human plasma-derived fibronectin (FN) on human subchondral mesenchymal progenitor cells regarding cell migration, proliferation, and chondrogenic differentiation. MATERIALS & METHODS: Human subchondral mesenchymal progenitor cells were analyzed for their migration capacity upon treatment with human plasma-derived FN. Proliferation activity was evaluated by DNA content. For chondrogenesis, cells were cultured in high-density pellet cultures in the presence of FN, TGFß3, and a combination thereof. RESULTS: Treatment of progenitors with FN significantly increased the number of migrating cells and elevated proliferative activity. Histological staining indicated formation of an extracellular matrix with type II collagen. Gene expression analysis gave no evidence for chondrogenic differentiation mediated by FN, but revealed a significant induction of type II collagen expression. CONCLUSION: FN has a potential to recruit human subchondral mesenchymal progenitor cells, possibly supporting proliferation and matrix assembly in cartilage repair procedures using bioactive implants after microfracture treatment.

Long-term outcomes after first-generation autologous chondrocyte implantation for cartilage defects of the knee.

BACKGROUND: Autologous chondrocyte implantation (ACI) represents an established surgical therapy for large cartilage defects of the knee joint. Although various studies report satisfying midterm results, little is known about long-term outcomes. PURPOSE: To evaluate long-term clinical and magnetic resonance imaging (MRI) outcomes after ACI. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between January 1997 and June 2001, a total of 86 patients were treated with ACI for isolated cartilage defects of the knee. The mean patient age at the time of surgery was 33.3 ± 10.2 years, and the mean defect size was 6.5 ± 4.0 cm(2). Thirty-four defects were located on the medial femoral condyle and 13 on the lateral femoral condyle, while 6 patients were treated for cartilage defects of the trochlear groove and 17 for patellar lesions. At a mean follow-up of 10.9 ± 1.1 years, 70 patients (follow-up rate, 82%) treated for 82 full-thickness cartilage defects of the knee were available for an evaluation of knee function using standard instruments, while 59 of these patients were additionally evaluated by 1.5-T MRI to quantify the magnetic resonance observation of cartilage repair tissue (MOCART) score. Clinical function at follow-up was assessed by means of the Lysholm score, the International Knee Documentation Committee (IKDC) score, and the Knee injury and Osteoarthritis Outcome Score (KOOS). Patient activity was assessed by the Tegner score. In addition, pain on a visual analog scale (VAS) and patient satisfaction were evaluated separately. RESULTS: At follow-up, 77% reported being "satisfied" or "very satisfied." The mean IKDC score at follow-up was 74.0 ± 17.3. The mean Lysholm score improved from 42.0 ± 22.5 before surgery to 71.0 ± 17.4 at follow-up (P < .01). The mean pain score on the VAS decreased from 7.2 ± 1.9 preoperatively to 2.1 ± 2.1 postoperatively. The mean MOCART score was 44.9 ± 23.6. Defect-associated bone marrow edema was found in 78% of the cases. Nevertheless, no correlation between the MOCART score and clinical outcome (IKDC score) could be found (Pearson coefficient, r = 0.173). CONCLUSION: First-generation ACI leads to satisfying clinical results in terms of patient satisfaction, reduction of pain, and improvement in knee function. Nevertheless, full restoration of knee function cannot be achieved. Although MRI reveals lesions in the majority of the cases and the overall MOCART score seems moderate, this could not be correlated with long-term clinical outcomes.

Is gender influencing the biomechanical results after autologous chondrocyte implantation?

PURPOSE: The influence of gender on the biomechanical outcome after autologous chondrocyte implantation (ACI) including isokinetic muscle strength measurements has not been investigated. The present prospective study was performed to evaluate gender-specific differences in the biomechanical function 48 months after ACI. METHODS: Fifty-two patients (mean age 35.6 ± 8.5 years) that met our inclusion criteria, underwent ACI with Bioseed C(®) and were evaluated with the KOOS score preoperatively, 6, 12 and 48 months after surgery. At final follow-up, 44 out of the 52 patients underwent biomechanical evaluation with isokinetic strength measurements of both knees. All data were evaluated separately for men and women and compared for each time interval using the Mann-Whitney U test. RESULTS: Clinical scores improved significantly over the whole study period (p < 0.05). Male patients demonstrated significantly better scores during the follow-up in the KOOS score (p < 0.05). Isokinetic strength measurements after 48 months revealed a significant strength deficit of the treated knee in all test modes compared to the healthy extremity (p < 0.05). Furthermore, male patients achieved significantly higher strength values compared to female patients (p < 0.05). CONCLUSIONS: ACI is a viable treatment option for full-thickness chondral defects in the knee of both genders. Isokinetic muscle strength measures are significantly worse in women (p < 0.05), but physiological and may play a role for the explanation of gender-specific results after ACI.

Fentanyl is less toxic on adult human mesenchymal stem cells compared to ropivacaine when used intraarticularly. A controlled in vitro study.

The purpose of this study was to evaluate the toxicity of ropivacaine and fentanyl on adult human mesenchymal stem cells (hMSC). hMSC's were seeded in monolayer triple-flasks and then plated into 96-well plates at a density of 5000 cells per well. After fully aspirating the culture medium, ropivacaine or fentanyl in its corresponding concentration (0.5%, 0.25%, 0.125% for ropivacaine and 0.05%, 0.025%, 0.0125% for fentanyl) or culture medium only was added to each well. After 30 min, the anaesthetic was removed and fresh culture medium was added. hMSCs mitochondrial activity as a marker of cell proliferation and apoptosis marker was evaluated after 1, 24 h and 7 days. Proliferation was significantly decreased after a 30 min exposure to 0.5% and 0.125% ropivacaine, respectively compared to the control group after 24 h (p < 0.001). Simultaneously, apoptosis was significantly induced. Proliferation of hMSC's was decreased after 24 h when exposed to 0.05%, 0.025% and 0.0125% fentanyl (p < 0.001). Apoptosis was only induced 24 h after an exposure to 0.05% fentanyl. Our data suggest that both drugs have a concentration-dependent effect on proliferation in adult hMSC's in vitro. This effect was more distinct with ropivacaine compared to fentanyl. Translating these results into clinical practice, this in vitro study suggests fentanyl as a potentially less toxic analgetic drug for intraarticular application after arthroscopic bone marrow stimulation or rotator cuff repair with comparable to prolonged pain reduction.

Influence of sex on the outcome of autologous chondrocyte implantation in chondral defects of the knee.

BACKGROUND: Sex-specific outcomes have been reported in anterior cruciate ligament reconstruction as well as in osteoarthrosis progression, but there are currently no related published data on autologous chondrocyte implantation (ACI). The present prospective study was performed to investigate sex-dependent differences in the results after ACI. HYPOTHESIS: The clinical and magnetic resonance imaging (MRI) results after ACI of the knee are influenced by the patient's sex. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The midterm clinical and MRI results of a cell-based fibrin-polymer graft for the treatment of full-thickness cartilage defects were evaluated preoperatively and 6, 12, and 48 months after surgery in 52 patients (male:female ratio, 25:27; average age, 35.6 years). Depending on the sex and the location of the defects (femoral condyles, n = 32; patellofemoral compartment, n = 20), patients were assigned to 4 different groups. Baseline clinical scores were compared with follow-up data by paired Wilcoxon tests for the Lysholm score and the International Knee Documentation Committee (IKDC) scoring system. Sex-specific differences were evaluated with the Mann-Whitney U test. The MRI evaluation was performed with the Henderson score at final follow-up. RESULTS: Clinical scores improved in all groups over the whole study period (P < .05). Compared with female patients, male patients achieved significantly better results in the Lysholm score at all time intervals and in the IKDC score at 6 and 12 months after surgery (P < .05). In a subgroup analysis, female patients with patellar defects had the worst results in both clinical scores. With the available number of patients, MRI evaluation at 48 months after surgery revealed no significant difference in defect fill between male and female patients (P > .05). The Pearson correlation coefficient between both clinical scores and the MRI parameters of defect fill and cartilage signal was significant (P < .05). CONCLUSION: Autologous chondrocyte implantation is a promising treatment option for full-thickness cartilage defects of male and female knee joints. Female patients with patellar defects have worse prognostic factors.