Comparison of Minced Cartilage Implantation with Autologous Chondrocyte Transplantation in an In Vitro Inflammation Model.

The current gold standard to treat large cartilage defects is autologous chondrocyte transplantation (ACT). As a new surgical method of cartilage regeneration, minced cartilage implantation (MCI) is increasingly coming into focus. The aim of this study is to investigate the influence of chondrogenesis between isolated and cultured chondrocytes compared to cartilage chips in a standardized inflammation model with the proinflammatory cytokine TNFα. Articular chondrocytes from bovine cartilage were cultured according to the ACT method to passage 3 and transferred to spheroid culture. At the same time, cartilage was fragmented (<1 mm3) to produce cartilage chips. TNFα (20 ng/mL) was supplemented to simulate an inflammatory process. TNFα had a stronger influence on the passaged chondrocytes compared to the non-passaged ones, affecting gene expression profiles differently between isolated chondrocytes and cartilage chips. MCI showed less susceptibility to TNFα, with reduced IL-6 release and less impact on inflammation markers. Biochemical and histological analyses supported these findings, showing a greater negative influence of TNFα on the passaged pellet cultures compared to the unpassaged cells and MCI constructs. This study demonstrated the negative influence of TNFα on chondrogenesis in a chondrocyte spheroid culture and cartilage fragment model. Passaged chondrocytes are more sensitive to cytokine influences compared to non-passaged cells and chondrons. This suggests that MCI may have superior regeneration potential in osteoarthritic conditions compared to ACT. Further investigations are necessary for the translation of these findings into clinical practice.

In Vitro Biocompatibility of the Novel Ceramic Composite Baghdadite for Defect Augmentation in Revision Total Hip Arthroplasty.

Biological augmentation of bony defects in weight-bearing areas of both the acetabulum and the femur remains challenging. The calcium-silicate-based ceramic Baghdadite is a very interesting material to be used in the field of revision total hip arthroplasty for the treatment of bony defects in weight-bearing and non-weight-bearing areas alike. The aim of this study was to investigate the biocompatibility of Baghdadite utilizing an osteoblast-like, human osteosarcoma cell line (MG-63) and the human monocytic leukemia-derived cell line (THP-1). THP-1-derived macrophages and MG-63 were indirectly exposed to Baghdadite for 7 days using a transwell system. Viability was assessed with MTT assay and pH analysis. To investigate proliferation rate, both cell lines were labelled using CFSE and flow cytometrically analyzed. ELISA was used to measure the secretion of IL-1ß, IL-6 and TNFα. The investigation of viability, while showing a slight difference in optical density for the MTT assays in MG-63 cells, did not present a meaningful difference between groups for both cell lines. The comparison of pH and the proportion of living cells between groups did not present with a significant difference for both THP-1 and MG-63. Baghdadite did not have a relevant impact on the proliferation rate of the investigated cell lines. Mean fluorescence intensity was calculated between groups with no significant difference. Baghdadite exerted a proinflammatory effect, which could be seen in an upregulated production of TNFα in macrophages. Production of IL-1ß and IL-6 was not statistically significant, but the IL-6 ELISA showed a trend to an upregulated production as well. A similar effect on MG-63 was not observed. No relevant cytotoxicity of Baghdadite ceramics was encountered. Baghdadite ceramics exhibit a proinflammatory potential by significantly increasing the secretion of TNFα in THP-1-derived macrophages. Whether this proinflammatory potential results in a clinically relevant effect on osteointegration is unclear and requires further investigation. Baghdadite ceramics provide an interesting alternative to conventional bone substitutes and should be further investigated in a biomechanical and in vivo setting.

Effects of single and repeated shock wave application on the osteogenic differentiation potential of human primary mesenchymal stromal cells and the osteoblastic cell line MG63 in vitro.

Introduction: Extracorporeal shock wave therapy is a non-invasive and effective option for treating various musculoskeletal disorders. Recent literature indicates that the parameters for extracorporeal shock wave therapy, such as the optimal intensity, treatment frequency, and localization, are yet to be determined. Studies reporting on the effects of shock wave application on primary mesenchymal stromal cells (MSCs) as well as osteoblastic cell lines in vitro are barely available and not standardized. Methods: In this study, we designed a special setup to precisely expose primary MSCs and the osteoblastic cell line MG63 to shock waves and subsequently analyzed the resulting cellular responses using standardized protocols to investigate their viability, proliferation behavior, cytokine secretion, and osteogenic differentiation potential in vitro. The shock wave transducer was coupled to a specifically designed water bath containing a 5 mL tube holder. Primary human MSCs and MG63 cells were trypsinated and centrifuged in a 5 mL tube and exposed to single and repeated shock wave application using different intensities and numbers of pulses. Results: Single treatment of MSCs using intensities 5, 10, 15, and 20 and pulse numbers 100, 250, 500, 750, and 1,000 at a constant pulse repetition frequency of 1 Hz resulted in a decreased viability and proliferation of both cell types with an increase in the intensity and number of pulses compared to controls. No significant difference in the osteogenic differentiation was observed at different time intervals in both cell types when a single shock wave application was performed. However, repeated shock wave sessions over three consecutive days of primary MSCs using low intensity levels 0.1 and 1 showed significant osteogenic differentiation 4-fold higher than that of the extracted Alizarin Red S at day 14, whereas MG63 cells showed no significant osteogenic differentiation compared to their corresponding controls. More specifically, repeated shock wave application triggered a significant downregulation of COL1A1, upregulation of RUNX2, and sustained increase of OCN in primary MSCs but not in the cell line MG63 when induced toward the osteogenic differentiation. Discussion: The effects of shock wave application on MSCs make it an effective therapy in regenerative medicine. We established a protocol to analyze a standardized shock wave application on MSCs and were able to determine conditions that enhance the osteogenic differentiation of MSCs in vitro.

Autologous minced cartilage repair for chondral and osteochondral lesions of the knee joint demonstrates good postoperative outcomes and low reoperation rates at minimum five-year follow-up.

PURPOSE: Minced cartilage is a one-step, autologous procedure with promising short-term results. The aim of the present study was to evaluate mid-term results in a patient cohort with chondral and osteochondral lesions in the knee joint treated with minced cartilage. METHODS: From 2015 through 2016, a total of 34 consecutive patients were treated with a single-step, autologous minced cartilage for knee chondral and osteochondral lesions. Numeric analogue scale (NAS) for pain and knee function were obtained prior to surgery and at 12, 24 and 60 months postoperatively. Secondary outcomes, including Lysholm score, Tegner activity score, and the International Knee Documentation Committee (IKDC) score, were recorded at final follow-up. MRI examinations of patients with unplanned radiological follow-up were analysed using the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score. RESULTS: A total of 28 patients (44.1% females, age at surgery: 29.5 ± 11.5 years) were available at a mean follow-up of 65.5 ± 4.1 months. Mean defect size was 3.5 ± 1.8 cm2. NAS for pain decreased from a median of 7 (range: 2-10) preoperatively to 2 (0-8) postoperatively. NAS knee function improved from a median of 7 (range: 2-10) to 3 (0-7) after five years, respectively. Satisfactory Lysholm (76.5 ± 12.5), IKDC (71.6 ± 14.8) and Tegner activity (4, range 3-9) scores were reported at final follow-up. Of all patients, 21(75%) and 19 (67.9%) reached or exceeded the PASS for the IKDC- and Lysholm score at final follow-up, respectively. The average overall MOCART 2.0 scores for all postoperatively performed MRIs (n = 23) was 62.3 ± 17.4. Four (14.2%) postoperative complications were directly linked to minced cartilage, one (3.5%) of which required revision surgery. CONCLUSION: One-step, autologous minced cartilage repair of chondral and osteochondral lesions of the knee without the necessity for subchondral bone treatment demonstrated good patient-reported outcomes, low complication rates, and graft longevity at mid-term follow-up. Minced cartilage represents a viable treatment option to more traditional cartilage repair techniques even in mid-term. LEVEL OF EVIDENCE: Level III.

Immunomodulatory potential of mesenchymal stromal cell-derived extracellular vesicles in chondrocyte inflammation.

Introduction: Osteoarthritis (OA) affects a large percentage of the population worldwide. Current surgical and nonsurgical concepts for treating OA only result in symptom-modifying effects. However, there is no disease-modifying therapy available. Extracellular vesicles released by mesenchymal stem/stromal cells (MSC-EV) are promising agents to positively influence joint homeostasis in the osteoarthritic surroundings. This pilot study aimed to investigate the effect of characterized MSC-EVs on chondrogenesis in a 3D chondrocyte inflammation model with the pro-inflammatory cytokine TNFα. Methods: Bovine articular chondrocytes were expanded and transferred into pellet culture at passage 3. TNFα, human MSC-EV preparations (MSC-EV batches 41.5-EVi1 and 84-EVi), EVs from human platelet lysate (hPL4-EV), or the combination of TNFα and EVs were supplemented. To assess the effect of MSC-EVs in the chondrocyte inflammation model after 14 days, DNA, glycosaminoglycan (GAG), total collagen, IL-6, and NO release were quantified, and gene expression of anabolic (COL-II, aggrecan, COMP, and PRG-4), catabolic (MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5), dedifferentiation (COL-I), hypertrophy (COL-X, VEGF), and inflammatory (IL-8) markers were analyzed; histological evaluation was performed using safranin O/Fast Green staining and immunohistochemistry of COL I and II. For statistical evaluation, nonparametric tests were chosen with a significance level of p < 0.05. Results: TNFα supplementation resulted in catabolic stimulation with increased levels of NO and IL-6, upregulation of catabolic gene expression, and downregulation of anabolic markers. These findings were supported by a decrease in matrix differentiation (COL-II). Supplementation of EVs resulted in an upregulation of the chondrogenic marker PRG-4. All MSC-EV preparations significantly increased GAG retention per pellet. In contrast, catabolic markers and IL-8 expression were upregulated by 41.5-EVi1. Regarding protein levels, IL-6 and NO release were increased by 41.5-EVi1. Histologic and immunohistochemical evaluations indicated a higher differentiation potential of chondrocytes treated with 84-EVi. Discussion: MSC-EVs can positively influence chondrocyte matrix production in pro-inflammatory surroundings, but can also stimulate inflammation. In this study MSC-EV 41.5-EVi1 supplementation increased chondrocyte inflammation, whereas MSC-84-EVi supplementation resulted a higher chondrogenic potential of chondrocytes in 3D pellet culture. In summary, the selected MSC-EVs exhibited promising chondrogenic effects indicating their significant potential for the treatment of OA; however, the functional heterogeneity in MSC-EV preparations has to be solved.

Biologic principles of minced cartilage implantation: a narrative review.

Cartilage tissue has a very limited ability to regenerate. Symptomatic cartilage lesions are currently treated by various cartilage repair techniques. Multiple treatment techniques have been proposed in the last 30 years. Nevertheless, no single technique is accepted as a gold standard. Minced cartilage implantation is a newer technique that has garnered increasing attention. This procedure is attractive because it is autologous, can be performed in a single surgery, and is therefore given it is cost-effective. This narrative review provides an overview of the biological potential of current cartilage regenerative repair techniques with a focus on the translational evidence of minced cartilage implantation.

Epidemiology and specific features of shoulder injuries in patients affected by epileptic seizures.

PURPOSE: Epileptic seizures can cause multiple shoulder injuries, the most common of which are dislocations, recurrent instability, fractures, and isolated lesions of the rotator cuff. Currently, only limited literature exists which describes the frequency and types of lesions in cohorts of epileptic patients and the corresponding treatment outcome. This study aims to document the occurrence of shoulder lesions in patients affected by seizures and to provide detailed information on trauma dynamics, specific lesion characteristics and treatment complications. METHODS: All patients referring to a tertiary epilepsy center were screened for shoulder injuries and the clinical records of those sustaining them during a seizure were reviewed. Demographic information, lesions' characteristics and trauma dynamics were analysed, as wells as-when carried out-the type of surgical intervention and any postoperative complications. RESULTS: The average age at the time of injury of 106 included patients was 39.7 ± 17.5 years and a male predominance was recorded (65%). Bilateral injuries occurred in 29 patients, simultaneously in 17 cases. A younger age, bilateral shoulder injuries and shoulder dislocations were significantly associated with the occurrence of a shoulder injury solely by muscular activation (p = 0.0054, p = 0.011, p < 0.0001). The complication rate in 57 surgically treated patients with follow-up data was 38.7%, with recurring instability being the most frequently reported complication (62.5%). CONCLUSIONS: Uncontrolled muscle activation during a seizure is a distinctive but not exclusive dynamic of injury in epileptic patients, accounting for more than the half of all shoulder lesions, especially in the younger. This can lead both to anterior and posterior dislocations or fracture-dislocations and is frequently cause of bilateral lesions and of instability recurrence after surgery. The high complication rates after surgical treatment in this selected subgroup of patients require that appropriate preventative measures are taken to increase the probability of treatment success. LEVEL OF EVIDENCE: Cohort study, level III.

Four decades of the Graf method in screening for developmental dysplasia of the hip (part I): Rightly the gold standard or of dubious benefit?

Introduction: The method of infant hip sonography according to Graf is used for general hip screening in Serbia, Austria, and Germany and is considered the gold standard. In other countries, such as the USA, however, it is not well accepted and is claimed to lead to high costs and overtreatment. The aim of this study was to investigate how many of the mentioned sources in a recent review article contained sonograms that met the quality criteria as taught in Graf's ultrasound courses. Methods: A systematic review published by Sakkers et al. was analyzed in terms of addressing the quality criteria of Graf's method. Studies that were suitable by title, abstract, manuscript, that contained an image of sonographic hip examination, and that were accessible were included into analysis. Results: Within the described review, there were 22 papers on the Graf method. Of these, 10 contained hip sonograms and were applicable for final analysis. The quality criteria according to Graf were not fulfilled within 5 of these 10 papers. Within these papers, there are examples of schematic sonograms that do not correspond with the quality criteria either. Conclusion: Skepticism regarding the Graf method may be based on user errors and insufficient application of the Graf quality assessment algorithm, which results in high intra- and inter-observer variations. Based on these findings, a working group was initiated to evaluate further work according to the same procedure (currently approximately 130 papers).

Four decades of developmental dysplastic hip screening according to Graf: What have we learned?

Purpose: Sonographic hip examination according to Graf is widely accepted standard for diagnosing developmental dysplastic hips (DDH) but it is criticized for alleged intra- and interobserver variations. This review was conducted to evaluate whether objective quality criteria according to the Graf method are fulfilled within scientific literature. Methods: A systematic literature search on Pubmed was performed using the search string: [(DDH) OR (Hip dysplasia)] AND (Graf). Studies suitable by title, abstract, manuscript, containing an image of sonographic hip examination and online accessibility were included into analysis. Results: 131 studies were included into final analysis. Only 68 (51.9%) presented correct sonographic images according Graf's criteria. 98 (74.8%) studies plotted alpha-angles (angle between bony roof line and base line) but only 85 (64.8%) studies beta-angles (angle between cartilage roof line and base line). Studies were contributed from 25 countries. Conclusion: Assumingly, skepticism regarding the Graf method is based on user errors and insufficient application of the Graf quality assessment algorithm resulting in high intra- and interobserver variations. When performed correctly, the Graf method is of high diagnostic value.

Mid-term Follow-Up after Closed Reduction in Developmental Dysplastic Hips.

PURPOSE: Closed reduction and subsequent spica casting is the gold standard for treatment of unstable or dislocated developmental dysplastic hips (DDHs). There are few data on mid-term results after treatment of DDH, especially on closed reduction. METHODS: Thirty-one consecutive patients with unstable or dislocated hips (n = 36) that were treated by fluoroscopic, contrast agent-supported closed reduction and spica casting were included and evaluated clinically and radiologically 2 and 5 years after treatment. RESULTS: After 2 and 5 years, there were no significant differences between healthy and successfully treated hips that were detectable with respect to acetabular coverage (AC) angle, center-edge angle, and clinical stability of the hip. There was a significant difference at the 2-year follow-up between healthy hips and hips that needed to undergo secondary open reduction surgery (n = 4) with respect to the AC angle (p < 0.001). CONCLUSION: Closed reduction in DDHs results in acceptable clinical and radiological results in the mid-term follow-up. It remains unclear why some patients with subsequent sonographically matured hips show secondary deterioration and recurrence of dysplasia.

Total endoscopic anterior pelvic approach (TAPA) - A new approach to the internal fixation of the symphysis.

This study presents a detailed documentation of a total endoscopic anterior pelvic approach (TAPA) for plate fixation of a symphyseal disruption. The purpose of this work is to describe a minimally invasive technique as a possible method for reducing complications and hospitalization. Other goals included giving technical recommendations and assessing potential pitfalls and problems of this new surgical approach. Surgery was performed in an interdisciplinary setting by an experienced orthopaedic and general surgeon. The first endoscopic approach used to visualize the injury was the same as is used for endoscopic hernia surgery. The repositioning of the symphysial rupture was achieved either through external fixation or indirectly with traction and a pelvic binder. Plate positioning and fixation were achieved through two additional, minimally invasive incisions. The endoscopic approach shows multiple advantages, such as no detachment of the rectus abdominis muscle and smaller skin incisions. Furthermore, this approach could lessen the incidence of hernia and postoperative pain. We see the presented technique as a simple and innovative surgical method for treating symphyseal disruption.

The psychological burden of a two-stage exchange of infected total hip and knee arthroplasties.

Infection is one of the most challenging complications after total joint arthroplasties affecting up to 30,000 patients in the US per year. This study investigates the psycho-social burden induced by the two-stage intervention in infected hip or knee replacements. All patients were treated with a two-stage exchange and were assessed at three different timepoints regarding their psychological conditions. Our findings suggest that psychological sequelae after treatment of periprosthetic joint infection are clearly underestimated in the literature and psychological correlates and side effects should be further highlighted during the training process of young surgeons.

[Cartilage chip transplantation for cartilage defects of the first metatarsophalangeal joint]. / Minced Cartilage bei Knorpeldefekten am Großzehengrundgelenk.

OBJECTIVE: Treatment of circumscribed cartilage defects in the first metatarsophalangeal joint (MTP1) using autologous cartilage fragments. INDICATIONS: Full thickness cartilage defects (ICRS IV) or focal osteoarthritis in combination with hallux rigidus. CONTRAINDICATIONS: Pre-existing ankylosis of the metatarsophalangeal joint; global osteoarthritis of the joint; advanced osteoarthritis of the sesamoidal articulation; osteonecrotic cysts in the head of the first metatarsal bone. SURGICAL TECHNIQUE: Preparation of the metatarsophalangeal joint. Mobilization of the first metatarsal head. Harvesting of the cartilage fragments from the dorsal rim portion as part of the cheilectomy. Mincing the cartilage fragments with a 3.0 mm shaver in sterile conditions. Augmenting the cartilage fragments with autologous conditioned plasma (ACP). Preparing the defect area and creation of a "contained" defect. Replantation of the resulting minced cartilage mass into the defect of the articular surface on the first metatarsal head. POSTOPERATIVE MANAGEMENT: Immobilization of the MTP1 for 48 h. Intensive physiotherapy for 3 months. Full weight bearing after reduced swelling. RESULTS: In 2020, 5 patients were treated with the method described and followed up for a period of 1 year. All patients were subjectively satisfied with the result of the operation. There were no relevant surgery-associated complications.

Autologous Minced Cartilage Implantation for Treatment of Chondral and Osteochondral Lesions in the Knee Joint: An Overview.

Cartilage defects in the knee are being diagnosed with increased frequency and are treated with a variety of techniques. The aim of any cartilage repair procedure is to generate the highest tissue quality, which might correlate with improved clinical outcomes, return-to-sport, and long-term durability. Minced cartilage implantation (MCI) is a relatively simple and cost-effective technique to transplant autologous cartilage fragments in a single-step procedure. Minced cartilage has a strong biologic potential since autologous, activated non-dedifferentiated chondrocytes are utilized. It can be used both for small and large cartilage lesions, as well as for osteochondral lesions. As it is purely an autologous and homologous approach, it lacks a significant regulatory oversight process and can be clinically adopted without such limitations. The aim of this narrative review is to provide an overview of the current evidence supporting autologous minced cartilage implantation.

Closed Reduction as Therapeutic Gold Standard for Treatment of Congenital Hip Dislocation. / Die geschlossene Reposition der Säuglingshüfte als therapeutischer Goldstandard der kongenitalen Hüftluxation.

BACKGROUND: Congenital hip dislocation (luxation) has an incidence of 0.4 - 0.7% and is regarded as a prearthrotic deformity. Thus, if not being diagnosed and treated at a very early age, extensive surgical measures are inevitable in childhood and early adulthood. METHODS: In the time between 01/2013 and 02/2019 we performed 28 600 hips sonographies in babies as part of general screening measures at U2 or U3. There were 71 instable, dysplastic or dislocated hips diagnosed that were treated by arthrographic, closed reduction. After a hip spica cast was applied, reposition was controlled by MRI, estimating the acetabular head index (ACI), the head coverage index (HCI) as well as the femoral head's sphericity or by sonography using the Graf method. RESULTS: Overall success rate was 91.6% for primary closed reduction. Patients with primarily irreducible hips were significantly older (p < 0.003) than patients with primarily successful reducible hips. Congenital dislocated hips had significantly higher ACIs (p < 0.001) and HCIs (p = 0.03) as well as significantly less well rounded femoral heads (sphericity; p < 0.001) compared to stable hips. CONCLUSION: Early diagnosis and treatment of congenital dislocated hips by closed reduction is essential for a sufficient and regular maturation of the hips without further surgical interventions.

Articular cartilage regeneration and tissue engineering models: a systematic review.

INTRODUCTION: Cartilage regeneration and restoration is a major topic in orthopedic research as cartilaginous degeneration and damage is associated with osteoarthritis and joint destruction. This systematic review aims to summarize current research strategies in cartilage regeneration research. MATERIALS AND METHODS: A Pubmed search for models investigating single-site cartilage defects as well as chondrogenesis was conducted and articles were evaluated for content by title and abstract. Finally, only manuscripts were included, which report new models or approaches of cartilage regeneration. RESULTS: The search resulted in 2217 studies, 200 of which were eligible for inclusion in this review. The identified manuscripts consisted of a large spectrum of research approaches spanning from cell culture to tissue engineering and transplantation as well as sophisticated computational modeling. CONCLUSIONS: In the past three decades, knowledge about articular cartilage and its defects has multiplied in clinical and experimental settings and the respective body of research literature has grown significantly. However, current strategies for articular cartilage repair have not yet succeeded to replicate the structure and function of innate articular cartilage, which makes it even more important to understand the current strategies and their impact. Therefore, the purpose of this review was to globally summarize experimental strategies investigating cartilage regeneration in vitro as well as in vivo. This will allow for better referencing when designing new models or strategies and potentially improve research translation from bench to bedside.

Autologous Chondrocyte Implantation in Osteoarthritic Surroundings: TNFα and Its Inhibition by Adalimumab in a Knee-Specific Bioreactor.

BACKGROUND: Autologous chondrocyte implantation (ACI) fails in up to 20% of cases. Advanced intra-articular degeneration paired with an inflammatory environment may be closely related to implantation failure. Certain cytokines have been identified to play a major role during early osteoarthritis. PURPOSE: To investigate the effects of tumor necrosis factor α (TNFα) and its potential inhibition by adalimumab on cartilage regeneration in an in vitro model of ACI. STUDY DESIGN: Controlled laboratory study. METHODS: Bovine articular chondrocytes were cultivated and transferred at passage 3 to fibrin-polyurethane scaffolds. Constructs were loaded by compression (10%-20% scaffold height) and shear (±25°) in a fully characterized multiaxial load (L) bioreactor to simulate clinical ACI or were subjected to free swelling (FS) conditions for a duration of 2 weeks. TNFα (20 ng/mL), adalimumab (10 µg/mL), or both were added to the medium. To assess the outcome, DNA, GAG (glycosaminoglycan), and total collagen were quantified, and gene expression of anabolic (collagen 2, aggrecan, cartilage oligomeric protein, proteoglycan 4), catabolic (matrix metalloproteinases [MMP] 3 and 13), dedifferentiation (collagen 1), and hypertrophy (collagen 10) markers and proinflammatory cytokines (TNFα, IL-1ß) was analyzed. Histological evaluation was performed with safranin O/fast green, toluidine blue, and immunohistochemistry of collagen 1 and 2. Apoptosis was analyzed by immunolabeling of anti-active caspase 3. For statistical evaluation, nonparametric tests were chosen with a significance level of P < .05. RESULTS: A general downregulation of anabolic and upregulation of catabolic markers was detected in the TNFα groups. Collagen 2 was suppressed by TNFα (FS, P = .029; L, P = .006), while MMP 3 was significantly upregulated (FS, P = .035; L, P = .001). Dynamic loading induced a chondrogenic response, which could not fully antagonize the effect of the cytokine. Adalimumab antagonized all effects of TNFα. The histological and immunohistochemical assessments demonstrated less matrix formation in the cytokine-only groups. TNFα induced apoptosis, and this effect was increased by loading. CONCLUSION: TNFα does negatively affect chondrogenesis under simulated ACI conditions. Both dynamic load and, more potentially, adalimumab showed the capability of antagonizing the negative effects. CLINICAL RELEVANCE: Catabolic cytokine suppression (ie, TNFα inhibition) combined with compression and shear load may best meet the conditions for chondrogenesis in an osteoarthritic environment.