Autologous Chondrocyte Implantation Technique Research Articles

Autologous chondrocyte implantation for the treatment of osteochondral lesions of the talus: What happens after 20 years?

BackgroundThe purpose of this study was to assess the long-term clinical efficacy of first-generation autologous chondrocyte implantation (ACI) technique for osteochondral lesions of the ankle joint. MethodsEleven patients with symptomatic OLTs underwent ACI from December 1997 to October 2002. A total of 9 patients (5 men, 4 women, age 25.2 ± 6.3) were evaluated at baseline and at 1, 3, 10 years, and at final follow-up of minimum 20 years with AOFAS ankle-hindfoot score, NRS for pain, and with the Tegner score. ResultsThe AOFAS score improved significantly from the baseline value of 40.4 ± 19.8 to 82.7 ± 12.9 at the final follow-up (p < 0.0005). The NRS for pain improved significantly from 7.8 ± 0.7 at baseline to 4.8 ± 2.1 at the final follow-up (p < 0.0005). Moreover, the Tegner score underwent a modification from the pre-operative median value of 1 (range: 1–3) and from a pre-injury value of 5 (range: 3–7) to 3 (range: 2–4) at the final follow-up (p < 0.0005). ConclusionsACI has proven to be an effective treatment option for patients suffering from OLTs, leading to a long-lasting clinical improvement even beyond 20 years of follow-up. Level of evidenceLevel IV

Is There an Association Between Authors' Conflicts of Interest and Outcomes in Clinical Studies Involving Autologous Chondrocyte Implantation?

Background:Autologous chondrocyte implantation (ACI) is an increasingly popular technique for the treatment of articular cartilage defects. Because several companies have financial interests in ACI, it is important to consider possible conflicts of interest when evaluating studies reporting outcomes of ACI.Purpose:To determine whether there is an association between authors’ financial conflicts of interest and the outcomes of ACI studies.Study Design:Cross-sectional study.Methods:A search of PubMed and MEDLINE databases for “autologous chondrocyte implantation” was performed. Clinical studies published after 2012 through May 15, 2019, and in English were included. Studies were determined to have financial conflicts of interest if any contributing author had relevant conflicts, either self-reported in the published study’s disclosures section or reported online in the American Academy of Orthopaedic Surgeons Disclosure database or the Centers for Medicare & Medicaid Services Open Payments database. The outcomes of each study were rated as favorable, equivocal, or unfavorable based on predefined criteria and then tested for association with conflicts of interest through use of the Fisher exact test.Results:A total of 79 studies met the inclusion criteria. Nearly all studies were of level 3 or 4 evidence. Conflicts of interest were established in 51.90% of studies (n = 41). Conflicts that were not self-reported by the authors were discovered in 18% of studies. The level of evidence was not associated with conflict of interest. No statistically significant difference was found in the rate of favorable outcomes between studies with conflicts (92.68%) and those with no conflicts (81.58%) (P = .126). Publications by US authors were more likely to have financial conflicts of interest (P = .003).Conclusion:Favorable results were reported in a majority of studies involving ACI. No statistical association was found between the frequency of favorable outcomes and the presence of financial conflicts of interest, country of authorship, or level of evidence. There was a trend toward more favorable outcomes in studies with conflicts of interest. Additionally, nearly 20% of publications had possible conflicts found online that were not self-reported. It is critical for orthopaedic surgeons to judiciously evaluate published studies and consider financial conflicts of interest before performing ACI techniques on patients.

Treatment of Osteochondral Lesions of the Talus With Matrix-induced Autologous Chondrocyte Implantation (MACI)

An osteochondral lesion of the talus is a common injury often resulting from an ankle fracture or ankle sprain. The role of nonoperative management is limited given the diminished healing capacity of these lesions. Among the available surgical options are cell-based techniques, which aim to regenerate hyaline-like articular cartilage. Matrix-induced autologous chondrocyte implantation is one such promising technique that has been validated as an effective and durable treatment option. This article reviews the matrix-induced autologous chondrocyte implantation technique and the evidence supporting its use.

Clinical, radiological, and histological outcomes after the fibrin-matrix autologous chondrocyte implantation for chondral lesions of the knee in patients more than 50 years old: A prospective case series with minimum 2-year follow-up.

The purpose of this study was to evaluate clinical and radiological outcomes and to analyze the histological findings of repaired cartilage in patients more than 50 years old with underwent fibrin-matrix autologous chondrocyte implantation (ACI). From January 2013 to February 2014, a prospective study was conducted on 16 patients (16 knees) who underwent fibrin-matrix ACI for International Cartilage Repair Society grade 3 or 4 chondral lesions of the knee. The major lesion was in the medial femoral condyle in all patients. The mean age of the patients was 58.1 ± 6.2 (range 51-66) years, and the minimum follow-up period was 2 years. All patients had clinical and radiological evaluations at 3 months, 6 months, 1 year, and 2 years after surgery. Twelve patients had second-look arthroscopies at 1 year after surgery, and implanted chondral biopsies were performed in 11 of these 12 patients for histological analysis. Functional disability assessment scales for the knee significantly improved after fibrin-matrix ACI (p < 0.05). The visual analog scale score significantly decreased from 6.7 ± 1.2 to 2.0 ± 1.8 (p < 0.001). The mean modified magnetic resonance observation of cartilage repair tissue score was 83.8 ± 17.3 at 1 year after surgery and 74.0 ± 19.2 at 2 years after surgery. Repair of the tissue with hyaline cartilage was confirmed histologically. Satisfactory clinical and radiological outcomes were obtained from gel-type fibrin-matrix ACI technique in older patients with a cartilage defect of the knee. Histological analysis confirmed that the new repaired tissue with hyaline cartilage filled the cartilage defect area. Therefore, fibrin-matrix ACI is believed to be an applicable treatment for older patients with chondral lesions of the knee. Level IV.

Arthroscopic autologous chondrocyte implantation in the knee with an in situ crosslinking matrix: minimum 4-year clinical results of 15 cases and 1 histological evaluation.

To clinically evaluate an arthroscopic autologous chondrocyte implantation (ACI) technique with an in situ crosslinking matrix for the treatment of full thickness cartilage defects of the knee and to present histological results of a graft cartilage biopsy obtained after 1.5years. Fifteen cases of arthroscopic autologous chondrocyte implantation in the knee performed between November 2011 and October 2012 were included in the study. Medical charts and operational reports were screened and the patients were contacted after 0.8 ± 0.3years (0.4-1.3) and 4.3 ± 0.3years (4.0-4.8) to asses subjective IKDC and re-operation. The Tegner activity scale was collected at the second follow-up time point. Subjective IKDC response rates were assessed at both follow-up time points. The first and second follow-up was completed by all 15 patients (100%). The subjective IKDC scores showed a significant improvement (pre-operative 44.5 ± 15.9, first follow-up 71.1 ± 15.9, p < 0.001, second follow-up 72.6 ± 17.3, p < 0.001). The overall response rate was 66.7% (n = 10) at follow-up one and two. There were no significant differences in pre-injury (4, range 1-9) and follow-up two (4, range 2-7) Tegner activity scales (p = n.s.). Two patients required re-operation in the index knee, not related to the ACI procedure. No complication related to the ACI or the implantation technique occurred. The histological results showed excellent cartilage regeneration. Arthroscopic ACI using an in situ crosslinking matrix is a safe and reliable treatment option for full-thickness cartilage defects of the knee.

Clinical outcome and subchondral bone oedema presence at two-year follow-up after high density autologous chondrocyte implantation treatment in the knee

BackgroundRecently, a new approach of autologous chondrocyte implantation technique (using as biomaterial a collagen type I/III membrane) based on increasing cell density called HD-ACI (high density autologous chondrocyte implantation) has been described. The objective of this paper was to study the clinical outcome and incidence of subchondral bone oedema in patients with cartilage lesions in the knee treated with HD-ACI at 1–2 years of follow-up. MethodsThis is a retrospective study performed with forty patients with chondral injuries grade III-IV. All patients were treated with HD-ACI with a cellular dose of 5×106 chondrocytes/cm2 of lesion. The subjective perception of improvement of symptoms and functionality was measured with the IKDC score (International Knee Documentation Committee). The presence of bone oedema was assessed at 6, 12 and 24 months of follow-up by magnetic resonance imaging. ResultsIKDC values showed a significant improvement at 12 and 24 months (p<.001). The mean difference of IKDC between the baseline visit and 12 months was 26.3 points, and 31.6 points at 24 months. Twenty-seven point five percent of the patients presented subchondral bone oedema at 2 years of follow-up. ConclusionsHD-ACI is an effective and safe treatment that improves pain, clinical perception and functionality of the joint. No correlation was found between the presence of bone oedema and the patients’ clinical outcome.

Evolución clínica y presencia de edema óseo subcondral a los dos años de tratamiento con implante de condrocitos autólogos de alta de densidad en la rodilla

BackgroundRecently, a new approach of autologous chondrocyte implantation technique (using as biomaterial a collagen type i/iii membrane) based on increasing cell density called HD-ACI (High Density Autologous Chondrocyte Implantation) has been described. The objective of this paper was to study the clinical outcome and incidence of subchondral bone oedema in patients with cartilage lesions in the knee treated with HD-ACI at 1-2 years of follow-up. MethodsThis is a retrospective study performed with forty patients with chondral injuries grade iii-iv. All patients were treated with HD-ACI with a cellular dose of 5×106 chondrocytes /cm2 of lesion. The subjective perception of improvement of symptoms and functionality was measured with the IKDC score (International Knee Documentation Committee). The presence of bone oedema was assessed at 6, 12 and 24 months of follow-up by magnetic resonance imaging. ResultsIKDC values showed a significant improvement at 12 and 24 months (P<.001). The mean difference of IKDC between the baseline visit and 12 months was 26.3 points, and 31.6 points at 24 months. Twenty-seven point five percent of the patients presented subchondral bone oedema at 2 years of follow-up. ConclusionsHD-ACI is an effective and safe treatment that improves pain, clinical perception and functionality of the joint. No correlation was found between the presence of bone oedema and the patients’ clinical outcome.

Matrix-Induced Autologous Chondrocyte Implantation With Autologous Bone Grafting for Osteochondral Lesions of the Femoral Trochlea

Matrix-induced autologous chondrocyte implantation is a 2-stage surgical procedure used to treat symptomatic, full-thickness chondral lesions of the knee. This third-generation autologous chondrocyte implantation (ACI) technique improves on the limitations of previous methods, including the risk of uneven chondrocyte distribution at the time of implantation and graft hypertrophy. Given the compliant properties of the scaffold, the graft can be easily shaped to treat irregular chondral defects and applied to articular surfaces with multiplanar geometry (e.g., patella, trochlea). Although ACI techniques are ideally suited to treat chondral surface defects, the ACI “sandwich” technique can be used to treat large osteochondral defects with significant bone loss (>8 mm). Historically, this procedure uses autologous bone graft to replace areas of osseous deficiency along with 2 type I/III collagen bilayer membranes to securely contain the cultured chondrocytes within the defect. We present an analogous technique for the treatment of osteochondral lesions of the femoral trochlea using a single matrix-induced ACI scaffold and autologous bone grafting for a segmental osseous defect.

Transcriptome-Wide Analysis of Human Chondrocyte Expansion on Synoviocyte Matrix.

Human chondrocytes are expanded and used in autologous chondrocyte implantation techniques and are known to rapidly de-differentiate in culture. These chondrocytes, when cultured on tissue culture plastic (TCP), undergo both phenotypical and morphological changes and quickly lose the ability to re-differentiate to produce hyaline-like matrix. Growth on synoviocyte-derived extracellular matrix (SDECM) reduces this de-differentiation, allowing for more than twice the number of population doublings (PD) whilst retaining chondrogenic capacity. The goal of this study was to apply RNA sequencing (RNA-Seq) analysis to examine the differences between TCP-expanded and SDECM-expanded human chondrocytes. Human chondrocytes from three donors were thawed from primary stocks and cultured on TCP flasks or on SDECM-coated flasks at physiological oxygen tension (5%) for 4 passages. During log expansion, RNA was extracted from the cell layer (70–90% confluence) at passages 1 and 4. Total RNA was column-purified and DNAse-treated before quality control analysis and next-generation RNA sequencing. Significant effects on gene expression were observed due to both culture surface and passage number. These results offer insight into the mechanism of how SDECM provides a more chondrogenesis-preserving environment for cell expansion, the transcriptome-wide changes that occur with culture, and potential mechanisms for further enhancement of chondrogenesis-preserving growth.

Combined autologous chondrocyte implantation and meniscus reconstruction for large chondral defect in the lateral compartment due to discoid lateral meniscus tear: A case report.

Discoid lateral meniscus tear leads to large chondral defect in the lateral compartment of the knee joint. There are few effective treatments for large chondral defect in both the tibial and femoral sides with severe degenerative lateral meniscus. We have developed a combined autologous chondrocyte implantation and meniscus reconstruction technique using hamstring tendon. This technique allows biological reconstruction and avoids knee arthroplasty.

Engineering Stem and Stromal Cell Therapies for Musculoskeletal Tissue Repair.

Stem cells and tissue-derived stromal cells stimulate the repair of degenerated and injured tissues, motivating a growing number of cell-based interventions in the musculoskeletal field. Recent investigations have indicated that these cells are critical for their trophic and immunomodulatory role in controlling endogenous cells. This Review presents recent clinical advances where stem cells and stromal cells have been used to stimulate musculoskeletal tissue repair, including delivery strategies to improve cell viability and retention. Emerging bioengineering strategies are highlighted, particularly toward the development of biomaterials for capturing aspects of the native tissue environment, altering the healing niche, and recruiting endogenous cells.

Improvement of the Chondrocyte-Specific Phenotype upon Equine Bone Marrow Mesenchymal Stem Cell Differentiation: Influence of Culture Time, Transforming Growth Factors and Type I Collagen siRNAs on the Differentiation Index.

Articular cartilage is a tissue characterized by its poor intrinsic capacity for self-repair. This tissue is frequently altered upon trauma or in osteoarthritis (OA), a degenerative disease that is currently incurable. Similar musculoskeletal disorders also affect horses and OA incurs considerable economic loss for the equine sector. In the view to develop new therapies for humans and horses, significant progress in tissue engineering has led to the emergence of new generations of cartilage therapy. Matrix-associated autologous chondrocyte implantation is an advanced 3D cell-based therapy that holds promise for cartilage repair. This study aims to improve the autologous chondrocyte implantation technique by using equine mesenchymal stem cells (MSCs) from bone marrow differentiated into chondrocytes that can be implanted in the chondral lesion. The optimized protocol relies on culture under hypoxia within type I/III collagen sponges. Here, we explored three parameters that influence MSC differentiation: culture times, growth factors and RNA interference strategies. Our results suggest first that an increase in culture time from 14 to 28 or 42 days lead to a sharp increase in the expression of chondrocyte markers, notably type II collagen (especially the IIB isoform), along with a concomitant decrease in HtrA1 expression. Nevertheless, the expression of type I collagen also increased with longer culture times. Second, regarding the growth factor cocktail, TGF-β3 alone showed promising result but the previously tested association of BMP-2 and TGF-β1 better limits the expression of type I collagen. Third, RNA interference targeting Col1a2 as well as Col1a1 mRNA led to a more significant knockdown, compared with a conventional strategy targeting Col1a1 alone. This chondrogenic differentiation strategy showed a strong increase in the Col2a1:Col1a1 mRNA ratio in the chondrocytes derived from equine bone marrow MSCs, this ratio being considered as an index of the functionality of cartilage. These data provide evidence of a more stable chondrocyte phenotype when combining Col1a1 and Col1a2 siRNAs associated to a longer culture time in the presence of BMP-2 and TGF-β1, opening new opportunities for preclinical trials in the horse. In addition, because the horse is an excellent model for human articular cartilage disorders, the equine therapeutic approach developed here can also serve as a preclinical step for human medicine.

Chondrogenic potential of IL-10 in mechanically injured cartilage and cellularized collagen ACI grafts.

The application of adjunctive mediators in Autologous chondrocyte implantation (ACI) techniques might be useful for improving the dedifferentiated chondrocyte phenotype, to support neocartilage formation and inhibit post-traumatic cartilage destruction. In this study we examined if (a) interleukin 10 treatment can cause chondrogenic phenotype stabilization and matrix preservation in mechanically injured cartilage and if (b) IL-10 can promote chondrogenesis in a clinically applied collagen scaffold for ACI treatment. For (a) bovine articular cartilage was harvested, subjected to an axial unconfined injury and treated with bovine IL-10 (1-10,000pg/ng/ml). For (b) a post-operatively remaining ACI graft was treated with human IL-10. Expression levels of type I/II/X collagen, SOX9 and aggrecan were measured by qPCR (a,b). After 3 weeks cell death was analyzed (nuclear blebbing and TUNEL assay) and matrix composition was determined by GAG measurements and immunohistochemistry (aggrecan, type I/II collagen, hyaluronic acid). One way ANOVA analysis with Bonferroni's correction. (a) IL-10 stabilized the chondrogenic phenotype after injurious compression and preserved matrix integrity. This was indicated by elevated expression of chondrogenic markers COL2A1, ACAN, SOX9, while COL1A1 and COL10A1 were reduced. An increased GAG content paralleled this and histological staining of type 2 collagen, aggrecan and toluidine blue were enhanced after 3 weeks. (b) IL-10 [100pg/ml] improved the chondrogenic differentiation of human chondrocytes, which was accompanied by cartilaginous matrix formation after 3 weeks of incubation. Interleukin-10 is a versatile adjuvant candidate to control the post-injurious environment in cartilage defects and promote chondrogenesis in ACI grafts.

Characterization and use of Equine Bone Marrow Mesenchymal Stem Cells in Equine Cartilage Engineering. Study of their Hyaline Cartilage Forming Potential when Cultured under Hypoxia within a Biomaterial in the Presence of BMP-2 and TGF-ß1

Articular cartilage presents a poor capacity for self-repair. Its structure-function are frequently disrupted or damaged upon physical trauma or osteoarthritis in humans. Similar musculoskeletal disorders also affect horses and are the leading cause of poor performance or early retirement of sport- and racehorses. To develop a therapeutic solution for horses, we tested the autologous chondrocyte implantation technique developed on human bone marrow (BM) mesenchymal stem cells (MSCs) on horse BM-MSCs. This technique involves BM-MSC chondrogenesis using a combinatory approach based on the association of 3D-culture in collagen sponges, under hypoxia in the presence of chondrogenic factors (BMP-2+TGF-β1) and siRNA to knockdown collagen I and HtrA1. Horse BM-MSCs were characterized before being cultured in chondrogenic conditions to find the best combination to enhance, stabilize, the chondrocyte phenotype. Our results show a very high proliferation of MSCs and these cells satisfy the criteria defining stem cells (pluripotency-surface markers expression). The combination of BMP-2+TGF-β1 strongly induces the chondrogenic differentiation of MSCs and prevents HtrA1 expression. siRNAs targeting Col1a1 and Htra1 were functionally validated. Ultimately, the combined use of specific culture conditions defined here with specific growth factors and a Col1a1 siRNAs (50nM) association leads to the in vitro synthesis of a hyaline-type neocartilage whose chondrocytes present an optimal phenotypic index similar to that of healthy, differentiated chondrocytes. Our results lead the way to setting up pre-clinical trials in horses to better understand the reaction of neocartilage substitute and to carry out a proof-of-concept of this therapeutic strategy on a large animal model.

Mechanical properties and structure-function relationships of human chondrocyte-seeded cartilage constructs after in vitro culture.

Autologous Chondrocyte Implantation (ACI) is a widely recognized method for the repair of focal cartilage defects. Despite the accepted use, problems with this technique still exist, including graft hypertrophy, damage to surrounding tissue by sutures, uneven cell distribution, and delamination. Modified ACI techniques overcome these challenges by seeding autologous chondrocytes onto a 3D scaffold and securing the graft into the defect. Many studies on these tissue engineered grafts have identified the compressive properties, but few have examined frictional and shear properties as suggested by FDA guidance. This study is the first to perform three mechanical tests (compressive, frictional, and shear) on human tissue engineered cartilage. The objective was to understand the complex mechanical behavior, function, and changes that occur with time in these constructs grown in vitro using compression, friction, and shear tests. Safranin-O histology and a DMMB assay both revealed increased sulfated glycosaminoglycan (sGAG) content in the scaffolds with increased maturity. Similarly, immunohistochemistry revealed increased lubricin localization on the construct surface. Confined compression and friction tests both revealed improved properties with increased construct maturity. Compressive properties correlated with the sGAG content, while improved friction coefficients were attributed to increased lubricin localization on the construct surfaces. In contrast, shear properties did not improve with increased culture time. This study suggests the various mechanical and biological properties of tissue engineered cartilage improve at different rates, indicating thorough mechanical evaluation of tissue engineered cartilage is critical to understanding the performance of repaired cartilage. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2298-2306, 2017.

Cell-Seeded Autologous Chondrocyte Implantation: A Simplified Implantation Technique That Maintains High Clinical Outcomes

Background: The use of autologous chondrocyte implantation (ACI) remains limited, even though multiple studies have demonstrated success rates exceeding 75%. The procedure is perceived as invasive and technically challenging, presenting barriers to more widespread adoption. Purpose/Hypothesis: The objective of this study was to investigate whether outcomes and the failure rate of a simplified ACI technique (cs-ACI) were comparable with those of the more complicated traditional technique of a chondrocyte suspension injected under a collagen membrane (cACI). We hypothesized that the change in technique would not negatively affect outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: Thirty-nine patients treated with the cs-ACI technique fulfilled the inclusion requirements. A group of 45 patients treated previously with standard cACI was used as a comparison. The functional outcomes were prospectively collected both preoperatively and postoperatively at the last follow-up. Failure was defined as any graft removal of more than 25% of the original defect size. Magnetic resonance imaging was performed postoperatively, and scans were assessed using a modified MOCART (magnetic resonance observation of cartilage repair tissue) scoring system. Results: Group demographics were not significantly different, except for the defect size and mean follow-up: 4.09 years in the cACI group and 2.46 years in the cs-ACI group. Significant improvements were seen in all outcome measures except the Tegner score from the preoperative baseline to the latest follow-up for both the cACI group (International Knee Documentation Committee [IKDC] score, from 42.0 to 63.4; Knee injury and Osteoarthritis Outcome Score [KOOS]–Pain subscore, from 58.7 to 77.1; Lysholm score, from 57.2 to 69.7; and Tegner score, from 3.5 to 4.2) and the cs-ACI group (IKDC score, from 45.6 to 68.0; KOOS-Pain subscore, from 66.6 to 84.7; Lysholm score, from 53.7 to 75.4; and Tegner score, from 3.2 to 3.8). No significant difference was found between the groups at the latest follow-up. The failure rate at 2 years was not significantly different, while the total failure rate over the entire study period was significantly lower in the cs-ACI group than the cACI group (5% vs 24%, respectively). The overall MOCART score was not significantly different between the groups. Conclusion: The treatment of full-thickness articular cartilage defects with a simplified cell-seeded ACI technique demonstrated no significant differences in the failure rate and patient-reported outcomes when compared with a standard technique utilizing interrupted sutures and the injection of a cell suspension under a collagen membrane.

Tri-layered composite plug for the repair of osteochondral defects: in vivo study in sheep

Cartilage defects are a source of pain, immobility, and reduced quality of life for patients who have acquired these defects through injury, wear, or disease. The avascular nature of cartilage tissue adds to the complexity of cartilage tissue repair or regeneration efforts. The known limitations of using autografts, allografts, or xenografts further add to this complexity. Autologous chondrocyte implantation or matrix-assisted chondrocyte implantation techniques attempt to introduce cultured cartilage cells to defect areas in the patient, but clinical success with these are impeded by the avascularity of cartilage tissue. Biodegradable, synthetic scaffolds capable of supporting local cells and overcoming the issue of poor vascularization would bypass the issues of current cartilage treatment options. In this study, we propose a biodegradable, tri-layered (poly(glycolic acid) mesh/poly(l-lactic acid)-colorant tidemark layer/collagen Type I and ceramic microparticle-coated poly(l-lactic acid)-poly(ϵ-caprolactone) monolith) osteochondral plug indicated for the repair of cartilage defects. The porous plug allows the continual transport of bone marrow constituents from the subchondral layer to the cartilage defect site for a more effective repair of the area. Assessment of the in vivo performance of the implant was conducted in an ovine model (n = 13). In addition to a control group (no implant), one group received the implant alone (Group A), while another group was supplemented with hyaluronic acid (0.8 mL at 10 mg/mL solution; Group B). Analyses performed on specimens from the in vivo study revealed that the implant achieves cartilage formation within 6 months. No adverse tissue reactions or other complications were reported. Our findings indicate that the porous biocompatible implant seems to be a promising treatment option for the cartilage repair.

Chondral defects in the knee: Are autologous bone marrow derived mesenchymal stem cells suitable to replace autologous chondrocyte implantation techniques? results from a mid-term observational cohort study

Chondral defects in the knee: Are autologous bone marrow derived mesenchymal stem cells suitable to replace autologous chondrocyte implantation techniques? results from a mid-term observational cohort study

Autologous Chondrocyte Implantation Using a Bilayer Collagen Membrane with Bone Graft and Anteromedialization of the Tibial Tubercle for the Treatment of a Large Osteochondral Defect in the Lateral Knee Trochlea: A Case Report.

Autologous chondrocyte implantation (ACI) is an established technique for the treatment of osteochondral lesions of the knee. For larger lesions with a substantial amount of bone loss, ACI using a bilayer collagen membrane with bone-grafting has been demonstrated to offer good to excellent results in the tibiofemoral joint, but little has been reported on its use in the patellofemoral joint. We report on the 2-year follow-up of this technique of ACI with bone-grafting used for the treatment of a large osteochondral defect in the lateral aspect of the trochlea of the knee in an 18-year-old, active female patient. This case illustrates that ACI with bone-grafting using such a "sandwich" technique can be an effective treatment option for osteochondral lesions of the trochlea in the knee.

Repair of partial thickness cartilage defects using cartilage extracellular matrix membrane-based chondrocyte delivery system in human Ex Vivo model.

Treatment options for partial thickness cartilage defects are limited. The purpose of this study was to evaluate the efficacy of the chondrocyte-seeded cartilage extracellular matrix membrane in repairing partial thickness cartilage defects. First, the potential of the membrane as an effective cell carrier was investigated. Secondly, we have applied the chondrocyte-seeded membrane in an ex vivo, partial thickness defect model to analyze its repair potential. After culture of chondrocytes on the membrane in vitro, cell viability assay, cell seeding yield calculation and cell transfer assay were done. Cell carrying ability of the membrane was also tested by seeding different densities of cells. Partial defects were created on human cartilage tissue explants. Cell-seeded membranes were applied using a modified autologous chondrocyte implantation technique on the defects and implanted subcutaneously in nude mice for 2 and 4 weeks. In vitro data showed cell viability and seeding yield comparable to standard culture dishes. Time dependent cell transfer from the membrane was observed. Membranes supported various densities of cells. Ex vivo data showed hyaline-like cartilage tissue repair, integrated on the defect by 4 weeks. Overall, chondrocyte-seeded cartilage extracellular membranes may be an effective and feasible treatment strategy for the repair of partial thickness cartilage defects.