Autologous Chondrocyte Transplantation Research Articles

Knee Cartilage Injuries in Football Players: Clinical Outcomes and Return to Sport After Surgical Treatment: A Systematic Review of the Literature.

To systematically review the literature and analyze clinical outcomes and return-to-sport after surgical management of cartilage injuries in football players. A systematic literature review was performed in August 2023 on PubMed, WebOfScience, and Cochrane Library to collect studies on surgical strategies for cartilage lesions in football players. Methodological quality and risk of bias were assessed with the modified Coleman Methodology score and RoB2 and RoBANS2 tools. Fifteen studies on 409 football players (86% men, 14% women) were included: nine prospective and two retrospective case series, one randomized controlled trial, one prospective comparative study, one case report, and one survey. Bone marrow stimulation (BMS) techniques were the most documented. The lesion size influenced the treatment choice: debridement was used for small lesions (1.1 cm2), BMS, osteochondral autograft transplantation (OAT), matrix-assisted autologous chondrocytes transplantation (MACT), and scaffold-augmented BMS for small/mid-size lesions (2.2-3.0 cm2), and autologous chondrocytes implantation (ACI) for larger lesions (5.8 cm2). The surgical options yielded different results in terms of clinical outcome and return-to-sport, with fastest recovery for debridement and scaffold-augmented BMS. The current evidence is limited with large methodological quality variation (modified Coleman Methodology score 43.5/100) and a high risk of bias. Decision-making in cartilage injuries seems to privilege early return-to-sport, making debridement and microfractures the most used techniques. The lesion size influences the treatment choice. However, the current evidence is limited. Further studies are needed to confirm these findings and establish a case-based approach to treat cartilage injuries in football players based on the specific patient and lesion characteristics and the treatments' potential in terms of both return-to-sport and long-term results. Systematic review, level IV.

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.

Sex does not influence the long-term outcome of matrix-assisted autologous chondrocyte transplantation.

Regenerative techniques for articular cartilage lesions demonstrated heterogeneous clinical results. Several factors may influence the outcome, with sex being one of the most debated. This study aimed at quantifying the long-term influence of sex on the clinical outcome obtained with a regenerative procedure for knee chondral lesions. Matrix-assisted autologous chondrocyte transplantation (MACT) was used to treat 235 knees which were prospectively evaluated with the International Knee Documentation Committee (IKDC), EuroQol visual analogue scale,and Tegner scores at 14-year mean follow-up. A multilevel analysis was performed with the IKDC subjective scores standardised according to the age/sex category of each patientand/or the selection of a match-paired subgroup to compare homogeneous men and women patients. At 14 years, men and women showed a failure rate of 10.7% and 28.8%, respectively (p < 0.0005). An overall improvement was observed in both sexes. Women had more patellar lesions and men more condylar lesions (p = 0.001), and the latter also presented a higher preinjury activity level (p < 0.0005). Men had significantly higher IKDC subjective scores at all follow-ups (at 14 years: 77.2 ± 18.9 vs.62.8 ± 23.1; p < 0.0005). However, the analysis of homogeneous match-paired populations of men and women, with standardised IKDC subjective scores, showed no differences between men and women (at 14 years: -1.6 ± 1.7 vs. -1.9 ± 1.6). Men and women treated with MACT for knee chondral lesions presented a significant improvement and stable long-term results. When both sexes are compared with homogeneous match-paired groups, they have similar results over time. However, women present more often unfavourable lesion patterns, which proved more challenging in terms of long-term outcome after MACT. Level II.

Two-Year Results of Injectable Matrix-Associated Autologous Chondrocyte Transplantation in the Hip Joint: Significant Improvement in Clinical and Radiological Assessment.

Articular cartilage defects are a prevalent consequence of femoroacetabular impingement (FAI) in young active patients. In accordance with current guidelines, large chondral lesions of the hip joint over 2 cm2 are recommended to be treated with matrix-associated, autologous chondrocyte transplantation (MACT); however, the conditions in the hip joint are challenging for membrane-based MACT options. Injectable MACT products can solve this problem. The purpose of the trial was to assess clinical and radiological outcomes 24 months after injectable MACT of focal chondral lesions caused by FAI. We present data of 21 patients with focal cartilage defects of the hip [3.0 ± 1.4 cm2 (mean ± SD)], ICRS Grade III and IV caused by CAM-type impingement, who underwent arthroscopic MACT (NOVOCART® Inject) and FAI correction. The outcome was evaluated with the patient-reported outcome instruments iHOT33 and EQ-5D-5L (index value and VAS), whilst graft morphology was assessed based on the MOCART score over a follow-up period of 24 months. The iHOT33 score increased significantly from 52.9 ± 21.1 (mean ± SD) preoperatively to 85.8 ± 14.8 (mean ± SD; p < 0.0001) 24 months postoperatively. The EQ-5D-5L index value (p = 0.0004) and EQ-5D VAS (p = 0.0006) showed a statistically significant improvement as well. MRI evaluation after 24 months showed successful integration of the implant in all patients with a complete defect filling in 11 of 14 patients. Injectable MACT for the treatment of full-thickness chondral lesions of the hip joint due to FAI in combination with FAI correction improved symptoms, function, and quality of life in the treated cohort. Alongside the treatment of the underlying pathology by the FAI correction, the developed cartilage defect can be successfully repaired by MACT, which is of considerable clinical relevance.

Patients with Small Acetabular Cartilage Defects Caused by Femoroacetabular Impingement Do Not Benefit from Microfracture

According to current recommendations, large cartilage defects of the hip over 2 cm2 are suggested to undergo autologous chondrocyte transplantation (ACT), while small defects should be treated with microfracture. We investigated if patients with small chondral defects of the hip joint (≤100 mm2) actually benefit from microfracture. In this retrospective multicenter cohort study 40 patients with focal acetabular cartilage defects smaller than 100 mm2 and of ICRS grade ≥2 caused by femoroacetabular impingement were included. Twenty-six unrandomized patients underwent microfracture besides treatment of the underlying pathology; in 14 patients cartilage lesions were left untreated during arthroscopy. Over a mean follow-up of 28.8 months patient-reported outcome was determined using the iHOT33 (international hip outcome tool) and the VAS (visual analog scale) for pain. The untreated group showed a statistically significant improvement of the iHOT33 after 12 (p = 0.005), 24 (p = 0.019), and 36 months (p = 0.002) compared to the preoperative score, whereas iHOT33 in the microfracture group did not reveal statistically significant changes over time. There was no significant difference between both groups on any time point. Regarding pain both groups did not show a significant improvement over time in the VAS. The subjective outcome of patients with small cartilage defects of the hip (≤100 mm2) improves 12 months after arthroscopic FAIS surgery without any cartilage treatment. However, no improvement could be seen after microfracture. Therefore, a reserved surgical treatment for small cartilage defects of the hip under preservation of the subchondral bone is recommended especially if a simultaneous impingement correction is performed.

Low postoperative complication rate with high survival rate and good clinical outcome 9 years after autologous chondrocyte transplantation of the knee joint

PurposeTo investigate postoperative complications and associated risk factors for failure following autologous chondrocyte transplantation (“ACT”) as well as its long-term survival and clinical function. It was hypothesized that ACT is a safe technique for cartilage repair with a low incidence of postoperative complications and rare rates of revision surgery combined with a high long-term survival and good to excellent clinical outcome in long-term-follow-up.MethodsAll patients undergoing ACT-Cs of the knee joint between 2006 and 2012 at the author’s institution were included in this retrospective study. Concomitant procedures had been performed if necessary. Early postoperative complications, revision surgeries, failure and risk factors for those events were evaluated 6 months after the surgery. Long-term clinical outcome was assessed using the Lysholm Score, the Tegner Score, a 10-grade scale for satisfaction and the Visual Analogue Scale (VAS) at a minimum follow-up of 9 years postoperatively. Long-term survival was calculated using revision surgeries, clinical failures and conversion procedures to create a Kaplan–Meier analysis. A subgroup analysis for different defect locations was performed. 139 patients were included in this study (27% female/ 73%male; age 26.7 [21.7; 35.2] years). The median defect size was 4.0 [3.0; 6.0] cm2 (40% medial femoral condyle (MFC), 17% lateral femoral condyle (LFC), 36% patella, 19% trochlea). 97 (70%) of the patients had undergone previous surgery and 84 (60%) underwent concomitant procedures.ResultsPostoperatively, 8% of patients had complications (4% bleeding, 2% arthrofibrosis, 2% infection), 7% of patients needed revision surgery. 12% of patients had a prolonged deficit in ROM, that did not require revision surgery. No significant difference in terms of complications was found between the patellofemoral and femorotibial group. Patients demonstrated good patient reported long-term outcomes 9–15 years after the index surgery (Tegner: 4.7 ± 1.8; VAS: 2.4 ± 2.1; Lysholm: 80 ± 14; satisfaction with operation: 7.3 ± 1.9). Survival rates were 88% at 9 years, 85% at 11 years, and 85% at 13 years after the index procedure. Reasons for failure included debridement of ACT (n = 4; 5%), revision ACT (n = 3, 3%), conversion to total knee arthroplasty (n = 3, 3%) and conversion to High tibial osteotomy (HTO) (n = 1; 1%)).ConclusionThe present study indicates ACT as an effective treatment option for femorotibial- as well as patellofemoral cartilage defects with a high long-term survival and low conversion rate as well as good long-term results regarding knee function and satisfaction. Postoperative complications needing revision surgery are rare. Prolongated deficits of range of motion appear frequently up to six months especially in patellofemoral defects, but can often be successfully addressed by intensified physiotherapy without requiring an arthrolysis.Level of evidenceLevel III.

Sandwich Technique for Large Osteochondral Lesions of the Knee.

ObjectiveTo evaluate whether a sandwich technique procedure for large osteochondral lesions (OCL) of the medial femur condyle reduces clinical symptoms and improves activity level as well as to assess repair tissue integration on MRI over 2 years.DesignTwenty-one patients (median age: 29 years, 18-44 years) who received matrix-associated autologous chondrocyte transplantation (MACT) combined with cancellous bone grafting at the medial femur condyle in a 1-step procedure were prospectively included. Patients were evaluated before surgery (baseline) as well as 3, 6, 12, and 24 months postoperatively, including clinical evaluation, Lysholm score, Tegner Activity Rating Scale, and MRI with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score and a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS).ResultsSeventeen patients were available for the 24-month (final) follow-up (4 dropouts). Lysholm significantly improved from 48 preoperatively stepwise to 95 at final follow-up (P < 0.05). Tegner improvement from 2.5 at baseline to 4.0 at final follow-up was not significant (P = 1.0). MOCART score improved significantly and stepwise from 65 at 3 months to 90 at 24 months (P < 0.05). Total WORMS improved from 14.5 at surgery to 7.0 after 24 months (P < 0.05). Body mass index and defect size at surgery correlated with total WORMS at final follow-up (P < 0.05) but did not correlate with clinical scores or defect filling.ConclusionMACT combined with cancellous bone grafting at the medial femoral condyle reduces symptoms continuously over 2 years. A 1-step procedure may reduce perioperative morbidity. However, despite improvements, patients’ activity levels remain low, even 2 years after surgery.

Paper 43: Long-term Outcomes of an All-Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation Technique

Objectives:To evaluate the long-term clinical and magnetic resonance imaging outcomes of patients treated with an all-arthroscopic matrix-assisted autologous chondrocyte transplantation (MACT) technique for articular cartilage lesions of the knee.Methods:A total of 63 patients (21 women, 42 men) with a mean age of 35 ± 9.2 years, were treated with an all-arthroscopic MACT technique for articular cartilage lesions of the knee. Patients were prospectively evaluated preoperatively and after 2, 5, and 10 years of the surgery using multiple clinical scores: Lysholm, Tegner, International Knee Documentation Committee (IKDC), and the Knee injury and Osteoarthritis Outcome Score (KOOS); as well as with magnetic resonance imaging (MRI) T2-mapping at the same time points. Failure was defined as a reoperation because of symptoms caused by the primary repaired defect or a patient improvement of <10 points in the IKDC subjective score between the preoperative value and the final follow-up value.Results:Patients showed statistically significant clinical improvement in all PROM scores at 2, 5, and 10 years postoperative (PO) compared to their preoperative status. MRI T2-Mapping values of the repaired tissue decreased from 59.0 ± 14.6 ms preoperatively to 44.4 ± 15.6 ms at 10 years PO (P= 0.008), showing no statistical differences compared to the native cartilage values (39.1 ± 4.0 ms, P= 0.398). A surgical failure rate of 1.5% was documented, which was increased to 33% when clinical failures were also considered. Among all the analyzed factors linked to the likelihood of failure, lesions >4cm2 were the only ones to show statistical significance (P= 0.024).Conclusions:Patients treated with this arthroscopic MACT technique showed good and long-lasting clinical outcomes, as well as close to native cartilage characteristics on MRI T2-mapping. A limited number of failures were observed at 10 years PO, with most failures being in the first two years after treatment. Big chondral lesions (>4cm2) were found to have a greater likelihood of failing.UPLOAD-https://planion-client-files.s3.amazonaws.com/AOSSM/blobs/9e2d9f3a-b8a0-4921-9952-144a0de7acd7/1/Base_Px_AMECI_-_Clinica_2.pdf UPLOAD-https://planion-client-files.s3.amazonaws.com/AOSSM/blobs/e39a94d5-bbc5-4e27-8493-786a2237cef3/1/Patient-Reported_Outcome_Measures_1.pdf UPLOAD-https://planion-client-files.s3.amazonaws.com/AOSSM/blobs/aba360a2-961d-4b2e-a4fa-1049626e23d3/1/MRI_T2-Mapping_2.pdf UPLOAD-https://planion-client-files.s3.amazonaws.com/AOSSM/blobs/d9c78782-8a61-446f-b0e7-24873b631a5a/1/kaplan_meier.pdf

Matrix-assisted autologous chondrocyte transplantation for treatment of focal chondral lesions in the knee: the Hospital Israelita Albert Einstein experience.

ABSTRACTObjective Phase 1 clinical trial to determine feasibility, safety, and efficacy of a new advanced cell therapy product for treatment of knee articular cartilage injuries.Methods Three participants with knee focal chondral lesions were included, with no signs of osteoarthritis. Chondrocytes were obtained through knee arthroscopy, cultured in collagen membrane for 3 weeks at the laboratory, subjected to tests to release the cell therapy product, and implanted. All patients underwent a specific 3-month rehabilitation protocol, followed by assessments using functional and imaging scales. The main outcome was the incidence of severe adverse events.Results Three participants were included and completed the 2-year follow-up. There was one severe adverse event, venous thrombosis of distal leg veins, which was no associated with therapy, was treated and left no sequelae. The clinical and radiological scales showed improvement in the three cases.Conclusion The preliminary results, obtained with the described methodology, allow concluding that this product of advanced cell therapy is safe and feasible. ReBEC platform registration number: RBR-6fgy76

Isolated Osteochondral Autograft Versus Allograft Transplantation for the Treatment of Symptomatic Cartilage Lesions of the Knee: A Systematic Review and Meta-analysis

Background: Focal cartilage lesions of the knee remain a difficult entity to treat. Current treatment options include arthroscopic debridement, microfracture, autograft or allograft osteochondral transplantation, and cell-based therapies such as autologous chondrocyte transplantation. Osteochondral transplantation techniques restore the normal topography of the condyles and provide mature hyaline cartilage in a single-stage procedure. However, clinical outcomes comparing autograft versus allograft techniques are scarce. Purpose: To perform a comprehensive systematic review and meta-analysis of high-quality studies to evaluate the results of osteochondral autograft and allograft transplantation for the treatment of symptomatic cartilage defects of the knee. Study Design: Systematic review and meta-analysis; Level of evidence, 2. Methods: A comprehensive search of the literature was conducted using various databases. Inclusion criteria were level 1 or 2 original studies, studies with patients reporting knee cartilage injuries and chondral defects, mean follow-up ≥2 years, and studies focusing on osteochondral transplant techniques. Exclusion criteria were studies with nonknee chondral defects, studies reporting clinical outcomes of osteochondral autograft or allograft combined with other procedures, animal studies, cadaveric studies, non–English language studies, case reports, and reviews or editorials. Primary outcomes included patient-reported outcomes and failure rates associated with both techniques, and factors such as lesion size, age, sex, and the number of plugs transplanted were assessed. Metaregression using a mixed-effects model was utilized for meta-analyses. Results: The search resulted in 20 included studies with 364 cases of osteochondral autograft and 272 cases of osteochondral allograft. Mean postoperative survival was 88.2% in the osteochondral autograft cohort as compared with 87.2% in the osteochondral allograft cohort at 5.4 and 5.2 years, respectively (P = .6605). Patient-reported outcomes improved by an average of 65.1% and 81.1% after osteochondral autograft and allograft, respectively (P = .0001). However, meta-analysis revealed no significant difference in patient-reported outcome percentage change between osteochondral autograft and allograft (P = .97) and a coefficient of 0.033 (95% CI, –1.91 to 1.98). Meta-analysis of the relative risk of graft failure after osteochondral autograft versus allograft showed no significant differences (P = .66) and a coefficient of 0.114 (95% CI, –0.46 to 0.69). Furthermore, the regression did not find other predictors (mean age, percentage of female patients, lesion size, number of plugs/grafts used, and treatment location) that may have significantly affected patient-reported outcome percentage change or postoperative failure between osteochondral autograft versus allograft. Conclusion: Osteochondral autograft and allograft result in favorable patient-reported outcomes and graft survival rates at medium-term follow-up. While predictors for outcomes such as mean age, percentage of female patients, lesion size, number of plugs/grafts used, and treatment location did not affect the comparison of the 2 cohorts, proper patient selection for either procedure remains paramount to the success and potentially long-term viability of the graft.

From Chondrocytes to Chondrons, Maintenance of Phenotype and Matrix Production in a Composite 3D Hydrogel Scaffold.

Osteoarthritis (OA) is a degenerative disease characterized by articular cartilage (AC) degradation that affects more than 30 million people in the USA. OA is managed with symptom-alleviating medications. Matrix-assisted autologous chondrocyte transplantation (MACT) is a tissue-engineered option, but current products are expensive and lack mechanical tunability or processability to match defect mechanical properties and anatomical shapes. Here, we explore the efficacy of a biocompatible hydrogel-based scaffold composed of sodium alginate, gelatin, and gum Arabic—referred to by SA–GEL–GA—to support bovine articular chondrocyte (bAChs) proliferation, pericellular matrix (PCM), and extracellular matrix (ECM) production. bAChs were grown for 45 days in SA–GEL–GA. Their viability, their live/dead status, histological staining, biochemical assays for glycosaminoglycans (GAGs) and collagen, atomic force microscopy (AFM) imaging, and immunofluorescence staining of collagen I, collagen II, aggrecan, and CD44 were assessed. We found that SA–GEL–GA was not cytotoxic, induced cellular proliferation by 6.1-fold while maintaining a round morphology, and supported ECM deposition by producing 3.9-fold more GAG compared to day 0. bAChs transformed into chondrons and produced a PCM enriched with collagen II (3.4-fold), aggrecan (1.7-fold), and CD44 (1.3-fold) compared to day 0. In summary, SA–GEL–GA supported the proliferation, ECM production, and PCM production of bAChs in vitro.

Surgical treatment of focal cartilage defects in the knee : Indications, techniques, modifications and results

The treatment strategies for focal cartilage damage in the knee are multifarious. For established procedures, such as microfracturing (MFX), autologous matrix-induced chondrogenesis (AMIC), osteochondral transplantation (OCT) and autologous chondrocyte transplantation (ACT), well-founded, partly comparative long-term studies and overlapping size-dependent differential indications are available. Innovative cell sources, the utilization of biological scaffolds as well as biologic agents and various combinations, have recently become the focus of scientific attention; however, high regulatory demands are restricting their use in Germany. The success of every procedure is dependent on the appropriate indications, the treatment of comorbidities, such as axis deviations or ligamentous instability, the surgeon's experience and an adequate follow-up treatment.

Freeze-Dried Curdlan/Whey Protein Isolate-Based Biomaterial as Promising Scaffold for Matrix-Associated Autologous Chondrocyte Transplantation-A Pilot In-Vitro Study.

The purpose of this pilot study was to establish whether a novel freeze-dried curdlan/whey protein isolate-based biomaterial may be taken into consideration as a potential scaffold for matrix-associated autologous chondrocyte transplantation. For this reason, this biomaterial was initially characterized by the visualization of its micro- and macrostructures as well as evaluation of its mechanical stability, and its ability to undergo enzymatic degradation in vitro. Subsequently, the cytocompatibility of the biomaterial towards human chondrocytes (isolated from an orthopaedic patient) was assessed. It was demonstrated that the novel freeze-dried curdlan/whey protein isolate-based biomaterial possessed a porous structure and a Young’s modulus close to those of the superficial and middle zones of cartilage. It also exhibited controllable degradability in collagenase II solution over nine weeks. Most importantly, this biomaterial supported the viability and proliferation of human chondrocytes, which maintained their characteristic phenotype. Moreover, quantitative reverse transcription PCR analysis and confocal microscope observations revealed that the biomaterial may protect chondrocytes from dedifferentiation towards fibroblast-like cells during 12-day culture. Thus, in conclusion, this pilot study demonstrated that novel freeze-dried curdlan/whey protein isolate-based biomaterial may be considered as a potential scaffold for matrix-associated autologous chondrocyte transplantation.

Thirty-eight-year outcome of osteochondral autograft transplantation in the knee joint: A case report

In 1985, we reported two cases of osteochondral autograft transplantation with the goal of repairing osteochondral defects in the knee joints of patients with osteochondritis dissecans using hyaline cartilage. Since then, osteochondral autograft transplantation, mosaicplasty, autologous chondrocyte transplantation, and allogeneic osteochondral transplantation have been developed and implemented as treatments for osteochondral defects. However, the long-term outcomes of these treatment modalities have not been hitherto reported. The patient was a 21-year-old man. He had medial extended type left knee joint osteochondritis dissecans osteochondral autograft transplantation was performed in 1980. A piece of osteochondral autograft was collected from the medial side of the trochlea and transplanted to the crater. Cancellous bone with cortical bone was transplanted from the ilium to the osteochondral collection site.There were neither subjective symptoms nor abnormal objective findings in the knee 38 years after. Radiographs showed small osteophytes in the medial tibiofemoral joint, and the patella skyline view showed narrowing of the medial patellofemoral joint space. On computed tomography, the bony part of the transplanted osteochondral autograft was fused with the surrounding bone tissue, and the trabecular pattern was similar to that of the original bone. A coronal section of a magnetic resonance imaging scan showed that the signal intensity of the transplanted cartilage was similar to that of the adjacent native cartilage. In the patellofemoral joint, the cartilage of the medial facet of the patella and trochlea was uneven. We reported 38-year outcomes in a patient who underwent osteochondral autograft transplantation in the knee joint. There were neither subjective symptoms nor abnormal objective findings in the knee. Imaging findings showed that a piece of osteochondral autograft filled the crater in the femoral condyle, and the superficial cartilage was considered to be alive.

Autologous chondrocyte transplantation with bone augmentation for the treatment of osteochodral defects of the knee : Treatment of osteochondral defects of the femoral condyles using autologous cancellous bone from the iliac crest combined with matrix-guided autologous chondrocyte transplantation

OperationszielOffene Therapie osteochondraler Läsionen des Kniegelenks zur vollständigen Auffüllung knöcherner Defekte und Wiederherstellung der Gelenkfläche.IndikationenFokale, symptomatische osteochondrale Defekte des Kniegelenks ab einer Knochendefekttiefe von ≥ 5 mm und Größe von ≥ 1,5 cm2.KontraindikationenArthrose (> KL Grad 2), „kissing lesions“ (ICRS > Grad 2), Alter > 50 Jahre, unbehandelte Bandinstabilitäten oder Beinachsenfehstellungen zum Nachteil des betroffenen Gelenkkompartiments, fehlendes Defektcontainment, entzündliche Gelenkerkrankungen.OperationstechnikZweizeitiger Eingriff: Ersteingriff (arthroskopische Knorpelprobenentnahme): Defektevaluierung, Entnahme von Knorpelstücken für die Chondrozytenkultivierung, bei Bedarf Behandlung von Begleitpathologien. Zweiteingriff (offene Defektbehandlung): Arthrotomie, Präparation des knöchernen Defekts, Auffüllung mit autologen Spongiosazylindern aus dem Beckenkamm, Knorpeldefektpräparation (kann größer als knöcherner Defekt sein) und matrixgestützte autologe Chondrozytentransplantation.WeiterbehandlungErsteingriff: frühfunktionelle Nachbehandlung mit schmerzorientierter Vollbelastung je nach Begleiteingriffen. Zweiteingriff: keine Drainage, funktionelle Kniegelenkorthese in Streckstellung für 1 Woche, danach schrittweise Freigabe der Flexion, Teilbelastung für 6 Wochen, Motorschiene (CPM) ab dem 1. postoperativen Tag.ErgebnisseSeit 2018 sind 8 Patienten (mittleres Alter 29,4 Jahre, Spanne 18 bis 36) mit der beschriebenen Technik behandelt worden. Alle Patienten konnten nach durchschnittlich 12 Monaten nachuntersucht werden. Der Gesamt-KOOS (Knee injury and Osteoarthritis Outcome Score) verbesserte sich im Mittel von 45,8 auf 81,3, und die postoperativen radiologischen Kontrollen zeigten die Einheilung der Spongiosazylinder bei allen Patienten. Der MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) Score ergab 80,4 Punkte.

7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage.

ObjectiveTo evaluate the morphological and biochemical quality of cartilage transplants and surrounding articular cartilage of patients 25 years after perichondrium transplantation (PT) and autologous chondrocyte transplantation (ACT) as measured by ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) and to present these findings next to clinical outcome.DesignSeven PT patients and 5 ACT patients who underwent surgery on the femoral condyle between 1986 and 1996 were included. Patient-reported outcome measures (PROMs) were assessed by the clinical questionnaires: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and Visual Analogue Scale (VAS) for knee pain. The morphological (MOCART score) and biochemical quality (glycosaminoglycans [GAGs] content and collagen integrity) of cartilage transplants and surrounding articular cartilage were analyzed by 7T MRI. The results of the PT and ACT patients were compared. Finally, a detailed morphological analysis of the grafts alone was performed.ResultsNo statistically significant difference was found for the PROMs and MOCART scores of PT and ACT patients. Evaluation of the graft alone showed poor repair tissue quality and high prevalence of intralesional osteophyte formation in both the PT and ACT patients. Penetration of the graft surface by the intralesional osteophyte was related to biochemically damaged opposing tibial cartilage; GAG content was significantly lower in patients with an osteophyte penetrating the graft surface.ConclusionsBoth PT and ACT patients have a high incidence of intralesional osteophyte formation 25 years after surgery. The resulting biochemical damage to the opposing tibial cartilage might be dependent on osteophyte morphology.

Early Efficacy of Type I Collagen-Based Matrix-Assisted Autologous Chondrocyte Transplantation for the Treatment of Articular Cartilage Lesions.

Background: Articular cartilage is a complex structure that allows for low frictional gliding and effective shock absorption. Various sports injuries and inflammatory conditions can lead to lesions in the articular cartilage, which has limited regenerative potential. Type I collagen combined with autologous chondrocytes in a three-dimensional culture were used to induce the regeneration of single-layer autologous expanded chondrocytes without chondrogenic differentiation. Purpose: To assess the clinical, radiological, and histological changes following collagen-based autologous chondrocyte transplantation (MACT) for chondral knee lesions. Methods: The study prospectively enrolled 20 patients with symptomatic knee chondral lesions (mean size lesion was 2.41 ± 0.43 cm2, range: 2.0–3.4 cm2) in the lateral femoral condyle and femoral groove who underwent type I collagen-based MACT between July 2017 and July 2019. knee injury and osteoarthritis outcome score (KOOS) was assessed before the procedure, and periodic clinical follow-up was conducted every 3 months for a maximum of 12 months following the procedure and at 1-year intervals thereafter. Magnetic resonance imaging (MRI) T2 mapping of repaired cartilage was also used for the quantitative analysis of regeneration. In one patient, second-look arthroscopy was performed to assess cartilage regeneration characteristics, and a portion of regenerated cartilage was harvested for histological evaluation 12 months after implantation. Results: At pre-operation and at three, six, 12, and 24 months after the operation, KOOS pain, symptoms, daily life activities, sports and recreation, as well as the quality of life were significantly improved between every two time points. Hematoxylin and eosin (HE) staining indicated that the newly formed cartilage was comprised of naive chondrocytes. Safranin O-fast (S-O) green staining of the regenerated tissue revealed fibroblast-like cells surrounded by glycosaminoglycans. Immunohistochemistry (IHC) analysis indicated that collagen type II was uniformly distributed at the deep zone of articular cartilage and type I collagen mainly depositing in the superficial cartilage layer. The T2 values for repaired tissue gradually decreased, eventually approaching near-average values. Conclusion: The present study demonstrated that type I collagen-based MACT is a clinically effective treatment for improving functionality and pain levels. Histological evidence confirmed hyaline cartilage induction and showed that repaired cartilage tended to emerge from the deep to the superficial layer. The quantitative MRI T2 mapping test indicated that there still was a difference between the transplanted cartilage and the surrounding hyaline cartilage. Taken together, the current method represents an efficient approach for the restoration of knee cartilage lesions.

Surgical treatment of focal cartilage defects in the knee : Indications, techniques, modifications and results

The treatment strategies for focal cartilage damage in the knee are multifarious. For established procedures, such as microfracturing (MFX), autologous matrix-induced chondrogenesis (AMIC), osteochondral transplantation (OCT) and autologous chondrocyte transplantation (ACT), well-founded, partly comparative long-term studies and overlapping size-dependent differential indications are available. Innovative cell sources, the utilization of biological scaffolds as well as biologic agents and various combinations, have recently become the focus of scientific attention; however, high regulatory demands are restricting their use in Germany. The success of every procedure is dependent on the appropriate indications, the treatment of comorbidities, such as axis deviations or ligamentous instability, the surgeon's experience and an adequate follow-up treatment.

Clinical evaluation after matrix-associated autologous chondrocyte transplantation : a comparison of four different graft types.

AimsThe aim of this retrospective study was to determine if there are differences in short-term clinical outcomes among four different types of matrix-associated autologous chondrocyte transplantation (MACT).MethodsA total of 88 patients (mean age 34 years (SD 10.03), mean BMI 25 kg/m2 (SD 3.51)) with full-thickness chondral lesions of the tibiofemoral joint who underwent MACT were included in this study. Clinical examinations were performed preoperatively and 24 months after transplantation. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) Subjective Knee Form, the Brittberg score, the Tegner Activity Scale, and the visual analogue scale (VAS) for pain. The Kruskal-Wallis test by ranks was used to compare the clinical scores of the different transplant types.ResultsThe mean defect size of the tibiofemoral joint compartment was 4.28 cm2 (SD 1.70). In total, 11 patients (12.6%) underwent transplantation with Chondro-Gide (matrix-associated autologous chondrocyte implantation (MACI)), 40 patients (46.0%) with Hyalograft C (HYAFF), 21 patients (24.1%) with Cartilage Regeneration System (CaReS), and 15 patients (17.2%) with NOVOCART 3D. The mean IKDC Subjective Knee Form score improved from 35.71 (SD 6.44) preoperatively to 75.26 (SD 18.36) after 24 months postoperatively in the Hyalograft group, from 35.94 (SD 10.29) to 71.57 (SD 16.31) in the Chondro-Gide (MACI) group, from 37.06 (SD 5.42) to 71.49 (SD 6.76) in the NOVOCART 3D group, and from 45.05 (SD 15.83) to 70.33 (SD 19.65) in the CaReS group. Similar improvements were observed in the VAS and Brittberg scores.ConclusionTwo years postoperatively, there were no significant differences in terms of outcomes. Our data demonstrated that MACT, regardless of the implants used, resulted in good clinical improvement two years after transplantation for localized tibiofemoral defects.Cite this article: Bone Joint Res 2021;10(7):370–379.

Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation Versus Microfracture: A 6-Year Follow-up of a Prospective Randomized Trial

Background: Few randomized controlled trials with a midterm follow-up have compared matrix-assisted autologous chondrocyte transplantation (MACT) with microfracture (MFx) for knee cartilage lesions. Purpose: To compare the structural, clinical, and safety outcomes at midterm follow-up of MACT versus MFx for treating symptomatic knee cartilage lesions. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 48 patients aged between 18 and 50 years, with 1- to 4-cm2 International Cartilage Repair Society (ICRS) grade III to IV knee chondral lesions, were randomized in a 1:1 ratio to the MACT and MFx treatment groups. A sequential prospective evaluation was performed using magnetic resonance imaging (MRI) T2 mapping, the MOCART (magnetic resonance observation of cartilage repair tissue) score, second-look arthroscopic surgery, patient-reported outcome measures, the responder rate (based on achieving the minimal clinically important difference for the Knee injury and Osteoarthritis Outcome Score [KOOS] pain and KOOS Sport/Recreation), adverse events, and treatment failure (defined as a reoperation because of symptoms caused by the primary defect and the detachment or absence of >50% of the repaired tissue during revision surgery). Results: Overall, 35 patients (18 MACT and 17 MFx) with a mean chondral lesion size of 1.8 ± 0.8 cm2 (range, 1-4 cm2) were followed up to a mean of 6 years postoperatively (range, 4-9 years). MACT demonstrated significantly better structural outcomes than MFx at 1 to 6 years postoperatively. At final follow-up, the MRI T2 mapping values of the repaired tissue were 37.7 ± 8.5 ms for MACT versus 46.4 ± 8.5 ms for MFx (P = .003), while the MOCART scores were 59.4 ± 17.3 and 42.4 ± 16.3, respectively (P = .006). More than 50% defect filling was seen in 95% of patients at 2 years and 82% at 6 years in the MACT group and in 67% at 2 years and 53% at 6 years in the MFx group. The second-look ICRS scores at 1 year were 10.7 ± 1.3 for MACT and 9.0 ± 1.8 for MFx (P = .001). Both groups showed significant clinical improvements at 6 years postoperatively compared with their preoperative status. Significant differences favoring the MACT group were observed at 2 years on the KOOS Activities of Daily Living (P = .043), at 4 years on all KOOS subscales (except Symptoms; P < .05) and the Tegner scale (P = .008), and at 6 years on the Tegner scale (P = .010). The responder rates at 6 years were 53% and 77% for MFx and MACT, respectively. There were no reported treatment failures after MACT; the failure rate was 8.3% in the MFx group. Neither group had serious adverse events related to treatment. Conclusion: Patients who underwent MACT had better structural outcomes than those who underwent MFx at 1 to 6 years postoperatively. Both groups of patients showed significant clinical improvements at final follow-up compared with their preoperative status. MACT showed superiority at 4 years for the majority of the KOOS subscales and for the Tegner scale at 4 to 6 years. The MACT group also had a higher responder rate and lower failure rate at final follow-up. Registration: NCT01947374 (ClinicalTrials.gov identifier).