Focal Articular Cartilage Lesions Research Articles

What Is the Best Way to Treat Focal Articular Cartilage Lesions of the Knee? Perhaps No Treatment at All: Commentary on an article by Thomas Birkenes, MD, et al.: "Long-Term Outcomes of Arthroscopically Verified Focal Cartilage Lesions in the Knee. A 19-Year Multicenter Follow-up with Patient-Reported Outcomes".

What Is the Best Way to Treat Focal Articular Cartilage Lesions of the Knee? Perhaps No Treatment at All: Commentary on an article by Thomas Birkenes, MD, et al.: "Long-Term Outcomes of Arthroscopically Verified Focal Cartilage Lesions in the Knee. A 19-Year Multicenter Follow-up with Patient-Reported Outcomes".

Management of Articular Cartilage Defects in the Knee: An Evidence-Based Algorithm

Focal articular cartilage lesions of the knee are a challenging disease entity due to the poor regenerative properties of hyaline cartilage that often lead to degenerative joint disease. Surgery is indicated to alleviate symptoms, restore function, and return to desired activities when conservative treatment fails. Providers must consider defect size and severity, compliance with the postoperative rehabilitation protocol including weight-bearing restrictions, and patient expectations in their clinical decision-making. Smaller defects may be treated with arthroscopic chondroplasty, bone marrow stimulation, and osteochondral autologous transfer. Alternative surgical options for larger defects include osteochondral restoration using fresh vs. cryopreserved allografts, autologous chondrocyte implantation, and particulated juvenile allograft cartilage. This article will review available treatment options and provide an evidence-based treatment algorithm to guide the orthopaedic clinician's clinical decision-making.

Comparison between articular chondrocytes and mesenchymal stromal cells for the production of articular cartilage implants.

Focal lesions of articular cartilage give rise to pain and reduced joint function and may, if left untreated, lead to osteoarthritis. Implantation of in vitro generated, scaffold-free autologous cartilage discs may represent the best treatment option. Here we compare articular chondrocytes (ACs) and bone marrow-derived mesenchymal stromal cells (MSCs) for their ability to make scaffold-free cartilage discs. Articular chondrocytes produced more extracellular matrix per seeded cell than mesenchymal stromal cells. Quantitative proteomics analysis showed that articular chondrocyte discs contained more articular cartilage proteins, while mesenchymal stromal cell discs had more proteins associated with cartilage hypertrophy and bone formation. Sequencing analysis revealed more microRNAs associated with normal cartilage in articular chondrocyte discs, and large-scale target predictions, performed for the first time for in vitro chondrogenesis, suggested that differential expression of microRNAs in the two disc types were important mechanisms behind differential synthesis of proteins. We conclude that articular chondrocytes should be preferred over mesenchymal stromal cells for tissue engineering of articular cartilage.

Scaffold-Free Engineering of Human Cartilage Implants.

ObjectiveDespite new strategies in tissue engineering, cartilage repair remains a major challenge. Our aim is to treat patients with focal lesions of articular cartilage with autologous hyaline cartilage implants using a scaffold-free approach. In this article, we describe experiments to optimize production of scaffold-free cartilage discs.DesignArticular chondrocytes were expanded in vitro, seeded in transwell inserts and redifferentiated using established chondrogenic components. Experimental variables included testing 2 different expansion media, adding bone morphogenetic protein 2 (BMP2), insulin-like growth factor 1 (IGF1), growth/differentiation factor 5 (GDF5), or fibroblast growth factor 18 (FGF18) to the differentiation medium and allowing the disc to float freely in large wells. Cartilage discs were analyzed by weight and thickness, real-time RT-qPCR (reverse transcriptase qualitative polymerase chain reaction), fluorescence immunostaining, transmission electron microscopy, second harmonic generation imaging, and measurement of Young’s modulus.ResultsAddition of BMP2 to the chondrogenic differentiation medium (CDM) was essential for stable disc formation, while IGF1, GDF5, and FGF18 were redundant. Allowing discs to float freely in CDM on a moving platform increased disc thickness compared with discs kept continuously in transwell inserts. Discs cultured for 6 weeks reached a thickness of almost 2 mm and Young’s modulus of >200 kPa. There was abundant type II collagen. Collagen fibrils were 25 nm thick, with a tendency to be organized perpendicular to the disc surface.ConclusionScaffold-free engineering using BMP2 and providing free movement in CDM produced firm, elastic cartilage discs with abundant type II collagen. This approach may potentially be used in clinical trials.

Efficacy of one-stage cartilage repair using allogeneic mesenchymal stromal cells and autologous chondron transplantation (IMPACT) compared to nonsurgical treatment for focal articular cartilage lesions of the knee: study protocol for a crossover randomized controlled trial

BackgroundArticular cartilage defects in the knee have poor intrinsic healing capacity and may lead to functional disability and osteoarthritis (OA). “Instant MSC Product accompanying Autologous Chondron Transplantation” (IMPACT) combines rapidly isolated recycled autologous chondrons with allogeneic MSCs in a one-stage surgery. IMPACT was successfully executed in a first-in-man investigator-driven phase I/II clinical trial in 35 patients. The purpose of this study is to compare the efficacy of IMPACT to nonsurgical treatment for the treatment of large (2–8 cm2) articular cartilage defects in the knee.MethodsSixty patients will be randomized to receive nonsurgical care or IMPACT. After 9 months of nonsurgical care, patients in the control group are allowed to receive IMPACT surgery. The Knee Injury and Osteoarthritis Outcome Score (KOOS), pain (numeric rating scale, NRS), and EuroQol five dimensions five levels (EQ5D-5 L) will be used to compare outcomes at baseline and 3, 6, 9, 12, and 18 months after inclusion. Cartilage formation will be assessed at baseline, and 6 and 18 months after inclusion using MRI. An independent rheumatologist will monitor the onset of a potential inflammatory response. (Severe) adverse events will be recorded. Lastly, the difference between IMPACT and nonsurgical care in terms of societal costs will be assessed by monitoring healthcare resource use and productivity losses during the study period. A health economic model will be developed to estimate the incremental cost-effectiveness ratio of IMPACT vs. nonsurgical treatment in terms of costs per quality adjusted life year over a 5-year time horizon.DiscussionThis study is designed to evaluate the efficacy of IMPACT compared to nonsurgical care. Additionally, safety of IMPACT will be assessed in 30 to 60 patients. Lastly, this study will evaluate the cost-effectiveness of IMPACT compared to nonsurgical care.Trial registrationNL67161.000.18 [Registry ID: CCMO]2018#003470#27 [EU-CTR; registered on 26 March 2019]NCT04236739 [ClinicalTrials.gov] [registered after start of inclusion; 22 January 2020]

Engineered nasal cartilage for the repair of osteoarthritic knee cartilage defects

Background & Aim Osteoarthritis (OA) is the most prevalent joint disorder causing pain and disability predominantly in the ageing population but also in young individuals. Current treatments are limited to alleviate symptoms, e.g. with anti-inflammatory drugs, until at the end stage of the disease the degenerated joint is replaced by a prosthetic implant. In this study we hypothesize that degenerative cartilage defects can be treated using Nasal chondrocyte-based Tissue Engineered Cartilage (N-TEC), as previously applied for the repair of focal articular cartilage lesions. In particular, we tested (i) the response of N-TECs to inflammatory factors, (ii) their capacity to modulate the inflammatory profile of OA joint cells in vitro as well as (iii) their survival in - and integration with OA tissues in vivo. Based on these results we then (iv) assessed the performance of N-TEC upon implantation in OA knee cartilage lesions of human patients. Methods, Results & Conclusion When N-TEC was exposed in vitro to inflammatory stimuli, as those found in OA joints (IL-1β/TNFα/IL-6 cytokines or factors secreted by OA synoviocytes) we demonstrate that it maintained its cartilaginous properties (i). Moreover, the secretome of N-TEC positively influenced the inflammatory profile of cells from OA joints, i.a. by reducing the expression of IL-6 and TNFα (ii). In vivo in an ectopic mouse model reproducing a human osteochondral OA tissue environment as well as in chronified articular cartilage defects in sheep, we further demonstrated cell survival and engraftment of N-TEC with the surrounding OA tissues (iii). Finally, we tested clinically the implantation of autologous N-TEC in two patients with advanced OA (Kellgren and Lawrence grade 3 and 4), who were otherwise considered for unicondylar knee arthroplasty. Patients reported reduced pain as well as improved joint function and life quality 14 months after surgery. In addition, a radiologically observed increase in joint space, indicating safety and feasibility of the treatment (iv). Together, our findings indicate that N-TEC can directly contribute to cartilage repair in OA joints. A phase II clinical trial is now required to assess efficacy in a larger cohort of OA patients.

Magnetic resonance imaging following cartilage repair of focal chondral lesions

Focal cartilage lesions are common pathologies of weight-bearing joints. Clinical presentation ranges from asymptomatic patients to severe, pain-related movement deficits. Moreover, focal chondral lesions are risk factors for the development of osteoarthritis. There are various treatment options involving both surgical and nonsurgical treatments. Musculoskeletal radiologists should be aware of the various surgical options as well as the postsurgical imaging characteristics to depict whether the encountered imaging findings reflect the normal postoperative course or are indicative of atreatment failure. We aim to describe the most common surgical procedures for the repair of focal cartilage lesions and their typical postsurgical appearance on MRI studies. The literature in PubMed was searched with the terms "focal articular cartilage lesions", "chondral lesions", "MOCART", "Microfracture", "Osteochondral Autograft Transfer", "mosaicplasty", "Osteochondral Allograft Transplantation", "OATS", "OCT", "Autologous Chondrocyte Implantation", "ACI", "Matrix-Assisted Chondrocyte Implantation", "Autologous Matrix-induced Chondrogenesis". Surgical methods for the treatment of focal cartilage lesions as well as the MR imaging features are explained.

Functional Results of Different Repair Techniques for Knee Articular Cartilage Lesions

The articular cartilage lesions are frequent and highly affect the patient�s quality of life. Although remarkable progress in the treatment of focal lesions of articular cartilage were lately made, controversies still exist regarding the treatment options. The main purpose of this study was to evaluate and compare the preoperative and 6 months postoperative knee functional scores of patients undergoing arthroscopic repair of knee chondral lesions by: debridement, microfractures, osteochondral autograft transplantation and autologous matrix-induced chondrogenesis. Chondral reconstruction with collagen membranes and osteochondral autograft transplantation techniques showed a superior result at 6 months postoperatively compared to microfracture techniques and mechanical debridement.

Trends in clinical trials for articular cartilage repair by cell therapy

Focal and degenerative lesions of articular cartilage greatly reduce the patient’s quality of life. Various therapies including surgical treatment have been developed, but a definitive therapy is not yet known. Several cell therapy products have already been developed and are available in the market. In this study, we examined the clinical research trends related to cell therapy products in the cartilage repair field based on data obtained from the ClinicalTrial.gov website. Although this website does not provide comprehensive results of clinical trials, it offers information on prospective clinical trials, including work in progress, and thus allows for chronological analysis of the data. We selected 203 studies related to the field of cartilage regeneration from ClinicalTrial.gov. The results showed a shift in the clinical translational trend in utilized cells from cartilage- and bone marrow- to adipose tissue-based cells. Whereas the studies that used cartilage as the cell source included many phase III trials, fewer studies using bone marrow and adipose tissue cells progressed to phase III, suggesting that most clinical developments using the latter sources have not been successful so far. One product covered the entire period from the start of phase I to the completion of phase III, with a time to completion of more than 100 months. Translational trends in autologous chondrocyte implantation were also discussed. The use of ClinicalTrials.gov as the sole data source can yield a perspective view of the global clinical translational trends, which has been difficult to observe up to this point.

Imaging of the Knee Following Repair of Focal Articular Cartilage Lesions.

Focal chondral or osteochondral lesions of the knee are common lesions involving either the cartilage layers or the cartilage layers and the subchondral bone. Despite their heterogeneous clinical presentation, they are important risk factors for the premature development of osteoarthritis. Therefore, early detection of osteochondral lesions and focal cartilage defects is crucial. In symptomatic (osteo-)chondral lesions, numerous therapeutic strategies, ranging from conservative treatment to surgical procedures such as marrow stimulation, osteochondral autograft transplantation, or autologous chondrocyte implantation are available. Musculoskeletal radiologists should be familiar with these surgical procedures, the evaluation of the postoperative findings as well as the possible complications when interpreting postoperative imaging studies. This review article describes the different surgical approaches to focal osteochondral lesions of the knee with emphasis on postoperative imaging findings and the pitfalls possibly encountered by the radiologist.

Trasplante osteocondral autólogo para tratar lesiones osteocondrales de la rodilla: evaluación de 62 pacientes con un seguimiento promedio de ocho años. [Osteochondral autograft transplantation for the treatment of osteochondral injuries of the knee: evaluation of 62 patients with an average follow-up of 8 years.

IntroducciónEl trasplante osteocondral autólogo es una alternativa quirúrgica en lesiones focales del cartílago articular. El objetivo de nuestro trabajo fue evaluar una serie de 62 pacientes tratados con mosaicoplastía de rodilla con 8 años promedio de seguimiento.Material y métodosEvaluamos retrospectivamente 62 pacientes operados con mosaicoplastía entre el año 2001 y 2014. Se incluyeron pacientes con lesión de cartílago focal de la rodilla a los que se les realizó mosaicoplastía aislada o asociada a otros procedimientos quirúrgicos (reconstrucción de LCA, osteotomía). Con un seguimiento mínimo de 2 años. Se evaluaron con las escalas de Lysholm e IKDC y el grado de artrosis con la escala radiográfica de Kellgren-Lawrence.ResultadosCuarenta y cinco fueron hombres y 17 mujeres. La edad promedio fue de 36 años. Treinta y cinco en cóndilo interno, 12 cóndilo externo, 12 tróclea y 3 combinadas. Cuarenta y dos fueron mosaicoplastías aisladas y 20 asociados a otro procedimiento. El resultado promedio de la escala de Lysholm al momento de la evaluación fue 80.1 y el IKDC fue 66.7. No encontramos diferencias significativas en la escala de Lysholm e IKDC entre los grupos de mosaicoplastía aislada y asociada a otro procedimiento. En 30 pacientes evaluados con radiografía se observó una inclusión satisfactoria del taco óseo.ConclusionesDentro de las opciones quirúrgicas se encuentran las microfracturas, el auto/alo injerto osteocondral y el implante de condrocitos autólogos. Todas estas técnicas han demostrado mejorar el estado clínico en comparación con el estado preoperatorio independientemente de cuál se utilice. En nuestra serie de pacientes operados con mosaicoplastía encontramos resultados satisfactorios en las evaluaciones clínicas.Consideramos que la mosaicoplastía es un procedimiento con alto grado de satisfacción y buenos resultados funcionales en pacientes con lesiones focales del cartílago articular. AbstractIntroduction: Osteochondral autograft transplantation is a surgical alternative for osteochondral defects of the knee. The aim of this study was to analyze a series of 62 patients treated with osteochondral autograft transplantation of the knee and an average follow-up of 8 years.Methods: A total of 62 patients treated with osteochondral autograft transplantation between 2001 and 2014 were evaluated. Patients with focal osteochondral lesions who underwent osteochondral autograft transplantation alone or associated with another procedure and a minimum follow-up of 2 years were included. Lysholm score, IKDC, and Kellgren- Lawrence radiographic scale were used. Forty-five men and 17 women (average age 36 years) were evaluated. Lesions were localized in medial condyle (35), lateral condyle (12), patella (12), and three were combined. Forty-two patients underwent isolated osteochondral autograft transplantation while 20 patients underwent associated surgical procedures.Results: Mean Lysholm score was 80.1 and IKDC score was 66.7. There were no significant differences in the Lysholm and IKDC scores between groups. Radiographic results demonstrated complete graft incorporation in 30 patients. Clinical evaluation revealed satisfactory results.Conclusion: Osteochondral autograft transplantation to treat osteochondral lesions is a procedure with a high clinical satisfaction and good functional results in patients with focal osteochondral lesions.

First Metatarsal Head Osteochondral Defect Treatment With Particulated Juvenile Cartilage Allograft Transplantation: A Case Series.

Focal damage to articular cartilage, also called an osteochondral defect (OCD), can be a cause of pain and decreased range of motion. Recent advancements have led to transplantation techniques using particulated juvenile articular cartilage allograft. This technique has been applied to the first metatarsal head to a very limited degree, with no published results to our knowledge. The aim of this study was to review the clinical results of patients who underwent particulated juvenile cartilage allograft implantation for first metatarsal head OCDs. We performed a retrospective consecutive case series study. Nine patients, at an average age of 41 years, were treated for symptomatic focal osteochondral defects of the first metatarsal head with particulate cartilage grafting from 2010 to 2016. Patients were contacted by phone to assess interest in returning to the office for follow-up, where weightbearing radiographs of the foot were obtained and a foot examination was performed. At an average follow-up of 3.3 years, 7 of 9 patients reported no pain with recreational activities and no patient required further operations. This patient cohort was physically active, with 6 of 9 listing running as a regular activity. The average overall American Orthopaedic Foot & Ankle Society (AOFAS) Hallux Metatarsophalangeal-Interphalangeal Scale questionnaire score was 85 (maximum 100), AOFAS pain 35.6 (maximum 40), and AOFAS function 40.1 (maximum 45). Patient satisfaction surveys correlated with the AOFAS scores and revealed that 7 of 9 patients were very satisfied with their results, 1 was satisfied, and 1 patient was very dissatisfied. Particulated juvenile cartilage allograft transplantation is a promising treatment option for symptomatic first metatarsophalangeal focal articular cartilage lesions. Further study is needed to demonstrate which lesions respond better to this type of cartilage graft versus traditional marrow-stimulating procedures. Level IV, retrospective case series.

Arthroscopic Mechanical Chondroplasty of the Knee Is Beneficial for Treatment of Focal Cartilage Lesions in the Absence of Concurrent Pathology.

Background:Articular cartilage lacks the ability for intrinsic repair after acute injury, and focal articular cartilage lesions cause significant morbidity worldwide. Arthroscopic debridement (chondroplasty) represents the majority of cartilage procedures of the knee; however, limited data exist regarding outcomes after chondroplasty performed in isolation of concurrent procedures or not as a primary treatment for osteoarthritis (OA).Hypothesis:Arthroscopic mechanical chondroplasty is beneficial for patients with a focal cartilage lesion of the knee in the absence of meniscal pathology or OA.Study Design:Case series; Level of evidence, 4.Methods:Potential participants were identified by querying billing data from a 3-year period in a single-surgeon practice, and eligible patients were verified to meet inclusion criteria through electronic medical record review. OA was quantified through Kellgren-Lawrence (KL) scoring. Subjective patient-reported outcome (PRO) scores, including International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), Tegner, Lysholm, and Veterans RAND 12-Item Health Survey (VR-12), were collected preoperatively and at follow-up intervals. International Cartilage Repair Society (ICRS) grade and lesion size were determined at arthroscopy. Linear regression was used to determine the effect of baseline score on final follow-up score. Correlated regression equations were used to assess the relationship of covariates and change in PRO scores.Results:Fifty-three of 86 (62%) eligible participants completed postoperative questionnaires at an average of 31.5 months (range, 11.5-57 months). The mean patient age was 37.3 ± 9.7 years and mean body mass index (BMI) was 27.7 ± 5.6 kg/m2; 33 (62%) participants were women. The mean treated lesion size was 3.3 ± 1.9 cm2, of these, 36 (68%) were ICRS grade 2 or 3, and 42 (79%) patients had a KL score of 0 to −2. On average, the cohort demonstrated significant improvement from baseline for almost all PRO scores. Regression analysis of change in score versus baseline indicated participants with lower preoperative scores gained more benefit from chondroplasty. Correlated regression equations showed KL score >0 and male sex had a consistent positive effect on change in PRO scores, high ICRS grade had a consistent negative effect, and lesion size, age, and obesity had no effect. Eight patients (15%) required further surgical intervention within the follow-up period.Conclusion:The clinical efficacy of chondroplasty for repair of focal cartilage defects of the knee has not been studied in isolation from concurrent orthopaedic procedures. Our data show that arthroscopic mechanical chondroplasty is beneficial to patients, and response to surgical intervention is correlated with baseline PRO scores, sex, ICRS grade, and KL score.

Magnetic Resonance Imaging Characterization and Clinical Outcomes After NeoCart Surgical Therapy as a Primary Reparative Treatment for Knee Cartilage Injuries

Background: Autologous cartilage tissue implants, including the NeoCart implant, are intended to repair focal articular cartilage lesions. Short-term results from United States Food and Drug Administration (FDA) phase I and phase II clinical trials indicated that the NeoCart implant was safe when surgically applied as a cell-based therapy and efficacious compared with microfracture. Hypothesis: Quantitative magnetic resonance imaging (MRI) analysis would reveal NeoCart tissue maturation through to 60-month follow-up. Study Design: Case series; Level of evidence, 4. Methods: Patients with symptomatic full-thickness cartilage lesions of the distal femoral condyle were treated with NeoCart in FDA clinical trials. Safety and efficacy were evaluated prospectively by MRI and clinical patient-reported outcomes (PROs) through to 60-month follow-up. Qualitative MRI metrics were quantified according to modified MOCART (magnetic resonance observation of cartilage repair tissue) criteria, with an independent evaluation of repair tissue signal intensity. Subjective PROs and objective range of motion (ROM) were obtained at baseline and through to 60 months. Results: Twenty-nine patients treated with NeoCart were observed over a mean of 52.0 ± 15.5 months (median, 60 months). MOCART analyses indicated significant improvement (P < .001) in cartilage quality from 3 to 24 months, with stabilization from 24 to 60 months. Signal intensity of the repair tissue evolved from hyperintense at early follow-up to isointense after 6 months and to hypointense after 24 months. The temporal progression toward hypointense T2 signals at later time points observed here indicated a further reorganization of the repair tissue toward a dense tissue that was less similar to the surrounding native tissue. However, 80% of patients showed evidence of subchondral bone changes on MRI at all time points; 4 patients (14%) showed no improvement of MRI criteria. Compared with baseline values, significant improvement (P < .001) was seen in PROs (mean [±SD] baseline to mean [±SD] final follow-up), including the International Knee Documentation Committee score (47.9 ± 17.4 to 75.5 ± 22.1), physical component summary of the Short Form–36 (40.5 ± 7.2 to 51.4 ± 8.1), and all 5 domains of the Knee injury and Osteoarthritis Outcome Score (Pain: 64.8 ± 12.1 to 86.1 ± 17.3; Activities of Daily Living: 75.5 ± 14.8 to 91.6 ± 13.8; Quality of Life: 28.6 ± 15.5 to 69.4 ± 28.0; Symptoms: 65.8 ± 13.8 to 86.6 ± 13.4; Sports and Recreation: 41.4 ± 24.3 to 72.4 ± 28.8). Significant (P < .0001) decreases from baseline scores for the visual analog scale for pain (34.6 ± 22.5) were seen by 6 months and sustained at final follow-up (14.3 ± 18.4). ROM significantly (P < .0001) improved from baseline (131.5° ± 7.9°) to final follow-up (140.7° ± 6.3°). Conclusion: Longitudinal MRI analysis demonstrated that NeoCart-based repair tissue is durable and evolves over time. For a majority of patients, this progression trended from an initial hyperintense signal to a hypointense signal at later follow-ups. Changes in radiographic measures over time corresponded with improvement in clinical measures, with maximum benefits experienced at 24-month follow-up. Similarly, clinical efficacy for the total cohort, determined by clinical outcome scores, reached a maximum at 24 months without decline to 60 months. Results from safety and exploratory clinical trials indicate that NeoCart is a safe and effective treatment for articular cartilage lesions through to 5-year follow-up. Registration: NCT00548119 (ClinicalTrials.gov identifier).

Osteochondral Defects of the Knee treated with Mosaicplasty. Results at Eight Years of Follow-Up

Objectives:There are several surgical options described for osteochondral defects of the knee depending on the size, location and condition of subchondral bone. The main indication for a mosaicplasty procedure is a less than 4 cm2 femoral condyle lesion. The purpose of this study was to analyze a series of patients treated with mosaicplasty with average eight years of follow-up.Methods:We retrospectively evaluated sixty-two patients with osteochondral defects of the knee who underwent a mosaicplasty between 2001 and 2014 with a minimum follow-up of 2 years. Patients were evaluated using the Lysholm score, International Knee Documentation Committee Score (IKDC) and Kellgren-Lawrence radiographic scale.Results:The mean Lysholm score was 80.1 and IKDC was 66.7. Forty-two patients had isolated mosaicplasty and 20 patients presented an associated surgical procedure (osteotomy, ACL reconstruction, meniscectomy). There were no significant differences between the Lysholm and IKDC scores in these two groups.Conclusion:We consider that mosaicplasty is a satisfactory procedure with good functional results in patients with focal articular cartilage lesions of the knee.

Cartilage tissue engineering: From biomaterials and stem cells to osteoarthritis treatments

Articular cartilage is a non-vascularized and poorly cellularized connective tissue that is frequently damaged as a result of trauma and degenerative joint diseases such as osteoarthrtis. Because of the absence of vascularization, articular cartilage has low capacity for spontaneous repair. Today, and despite a large number of preclinical data, no therapy capable of restoring the healthy structure and function of damaged articular cartilage is clinically available. Tissue-engineering strategies involving the combination of cells, scaffolding biomaterials and bioactive agents have been of interest notably for the repair of damaged articular cartilage. During the last 30 years, cartilage tissue engineering has evolved from the treatment of focal lesions of articular cartilage to the development of strategies targeting the osteoarthritis process. In this review, we focus on the different aspects of tissue engineering applied to cartilage engineering. We first discuss cells, biomaterials and biological or environmental factors instrumental to the development of cartilage tissue engineering, then review the potential development of cartilage engineering strategies targeting new emerging pathogenic mechanisms of osteoarthritis.

Intermittent applied mechanical loading induces subchondral bone thickening that may be intensified locally by contiguous articular cartilage lesions

SummaryObjectivesChanges in subchondral bone (SCB) and cross-talk with articular cartilage (AC) have been linked to osteoarthritis (OA). Using micro-computed tomography (micro-CT) this study: (1) examines changes in SCB architecture in a non-invasive loading mouse model in which focal AC lesions are induced selectively in the lateral femur, and (2) determines any modifications in the contralateral knee, linked to changes in gait, which might complicate use of this limb as an internal control.MethodsRight knee joints of CBA mice were loaded: once with 2weeks of habitual use (n = 7), for 2weeks (n = 8) or for 5weeks (n = 5). Both left (contralateral) and right (loaded) knees were micro-CT scanned and the SCB and trabecular bone analysed. Gait analysis was also performed.ResultsThese analyses showed a significant increase in SCB thickness in the lateral compartments in joints loaded for 5weeks, which was most marked in the lateral femur; the contralateral non-loaded knee also showed transient SCB thickening (loaded once and repetitively). Epiphyseal trabecular bone BV/TV and trabecular thickness were also increased in the lateral compartments after 5 weeks of loading, and in all joint compartments in the contralateral knee. Gait analysis showed that applied loading only affected gait in the contralateral himd-limb in all groups of mice from the second week after the first loading episode.ConclusionsThese data indicate a spatial link between SCB thickening and AC lesions following mechanical trauma, and the clear limitations associated with the use of contralateral joints as controls in such OA models, and perhaps in OA diagnosis.

One-step cartilage repair in the knee: collagen-covered microfracture and autologous bone marrow concentrate. A pilot study.

Different single-stage surgical approaches are currently under evaluation to repair cartilage focal lesions. To date, only little is known on even short-term clinical follow-up and almost no knowledge exists on histological results of such treatments. The present paper aims to analyze the clinical and histological results of the collagen-covered microfracture and bone marrow concentrate (C-CMBMC) technique in the treatment of focal condylar lesions of knee articular cartilage. Nine patients with focal lesions of the condylar articular cartilage were consecutively treated with arthroscopic microfractures (MFX) covered with a collagen membrane immersed in autologous bone marrow concentrate (BMC) from the iliac crest. Patients were retrospectively assessed using several standardized outcome assessment tools and MRI scans. Four patients consented to undergo second look arthroscopy and biopsy harvest. Every patient was arthroscopically treated for a focal condylar lesion (mean area 2.5 SD(0.4) cm(2)). All the patients (mean age 43 SD(9) years) but one experienced a significant clinical improvement from the pre-operative condition to the latest follow-up (mean 29 SD(11) months). Cartilage macroscopic assessment at 12 months revealed that all the repairs appeared almost normal. Histological analysis showed a hyaline-like cartilage repair in one lesion, a fibrocartilaginous repair in two lesions and a mixture of both in one lesion. The first clinical experience with single-stage C-CMBMC for focal cartilage defects in the knee suggests that it is safe, it improves the short-term knee function and that it has the potential to recreate hyaline-like cartilage.

Single-Stage Cell-Based Cartilage Regeneration Using a Combination of Chondrons and Mesenchymal Stromal Cells

Background: Autologous chondrocyte implantation (ACI) is traditionally a 2-step procedure used to repair focal articular cartilage lesions. With use of a combination of chondrons (chondrocytes in their own territorial matrix) and mesenchymal stromal cells (MSCs), ACI could be innovated and performed in a single step, as sufficient cells would be available to fill the defect within a 1-step surgical procedure. Chondrons have been shown to have higher regenerative capacities than chondrocytes without such a pericellular matrix. Purpose: To evaluate cartilage formation by a combination of chondrons and MSCs in vitro and in both small and large animal models. Study Design: Controlled laboratory study. Methods: Chondrons and MSCs were cultured at different ratios in vitro containing 0%, 5%, 10%, 20%, 50%, or 100% chondrons (n = 3); embedded in injectable fibrin glue (Beriplast); and implanted subcutaneously in nude mice (n = 10; ratios of 0%, 5%, 10%, and 20% chondrons). Also, in a 1-step procedure, a combination of chondrons and MSCs was implanted in a freshly created focal articular cartilage lesion (10% chondrons) in goats (n = 8) and compared with microfracture. The effect of both treatments, after 6-month follow-up, was evaluated using biochemical glycosaminoglycan (GAG) and GAG/DNA analysis and scored using validated scoring systems for macroscopic and microscopic defect repairs. Results: The addition of MSCs to chondron cultures enhanced cartilage-specific matrix production as reflected by a higher GAG production (P < .03), both in absolute levels and normalized to DNA content, compared with chondrocyte and 100% chondron cultures. Similar results were observed after 4 weeks of subcutaneous implantation in nude mice. Treatment of freshly created cartilage defects in goats using a combination of chondrons and MSCs in Beriplast resulted in better microscopic, macroscopic, and biochemical cartilage regeneration (P ≤ .02) compared with microfracture treatment. Conclusion: The combination of chondrons and MSCs increased cartilage matrix formation, and this combination of cells was safely applied in a goat model for focal cartilage lesions, outperforming microfracture. Clinical Relevance: This study describes the bench-to-preclinical development of a new cell-based regenerative treatment for focal articular cartilage defects that outperforms microfracture in goats. In addition, it is a single-step procedure, thereby making the expensive cell expansion and reimplantation of dedifferentiated cells, as in ACI, redundant.

Single-stage cartilage repair in the knee with microfracture covered with a resorbable polymer-based matrix and autologous bone marrow concentrate

BackgroundDifferent single-stage surgical approaches are currently under evaluation to repair focal cartilage lesions. This study aims to analyze the clinical and histological results after treatment of focal condylar articular lesions of the knee with microfracture and subsequent covering with a resorbable polyglycolic acid/hyaluronan (PGA -HA) matrix augmented with autologous bone marrow concentrate (BMC). MethodsNine patients with focal lesions of the condylar articular cartilage were consecutively treated with arthroscopic PGA -HA-covered microfracture and bone marrow concentrate (PGA -HA-CMBMC). Patients were retrospectively assessed using standardized assessment tools and magnetic resonance imaging (MRI). Five patients consented to undergo second look arthroscopy and 2 consented biopsy harvest. ResultsAll the patients but one showed improvement in clinical scoring from the pre-operative situation to the latest follow-up (average 22±2months). The mean IKDC subjective score, Lysholm score, VAS and the median Tegner score significantly increased from baseline to the latest follow-up. Cartilage macroscopic assessment at 12months revealed that one repair appeared normal, three almost normal and one appeared abnormal. Histological analysis proofed hyaline-like cartilage repair tissue formation in one case. MRI at 8 to 12months follow-up showed complete defect filling. ConclusionsThe first clinical experience with single-stage treatment of focal cartilage defects of the knee with microfracture and covering with the PGA -HA matrix augmented with autologous BMC (PGA -HA-CMBMC) suggests that it is safe, it improves knee function and has the potential to regenerate hyaline-like cartilage. Level of evidenceIV, case series.