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Concept: Autologous chondrocyte implantation


PURPOSE: Graft hypertrophy is a major complication in the treatment for localized cartilage defects with autologous chondrocyte implantation (ACI) using periosteal flap and its further development, Novocart (a matrix-based ACI procedure). The aim of the present study is to investigate individual criteria for the development of graft hypertrophy by NOVOCART 3D implantation of the knee in the post-operative course of 2 years. METHODS: Forty-one consecutive patients with 44 isolated cartilage defects of the knee were treated with NOVOCART 3D implants. Individual criteria and defect-associated criteria were collected. Follow-up MRIs were performed at 3, 6, 12 and 24 months. The NOVOCART 3D implants were measured and classified. The modified MOCART Score was used to evaluate quality and integration of the NOVOCART 3D implants in MRI. RESULTS: Graft hypertrophy was observed in a total of 11 patients at all post-operative time points. We were able to show that NOVOCART 3D implantation of cartilage defects after acute trauma and osteochondritis dissecans (OCD) led to a significantly increased proportion of graft hypertrophy. No other individual criteria (age, gender, BMI) or defect-associated criteria (concomitant surgery, second-line treatment, defect size, fixation technique) showed any influence on the development of graft hypertrophy. The modified MOCART Score results revealed a significant post-operative improvement within 2 years. CONCLUSION: The aetiology of cartilage defects appears to have a relevant influence for the development of graft hypertrophy. Patients, who were treated with NOVOCART 3D implants after an acute event (acute trauma or OCD), are especially at risk for developing a graft hypertrophy in the post-operative course of two years. LEVEL OF EVIDENCE: Case series, Level IV.

Concepts: Cartilage, Magnetic resonance imaging, Knee, Knee cartilage replacement therapy, Knee replacement, Autologous chondrocyte implantation, Osteochondritis dissecans


Previous experimental studies have determined local strain fields for both healthy and degenerated cartilage tissue during mechanical loading. However, the biomechanical response of chondrocytes in situ, and in particular, the response of the actin cytoskeleton to physiological loading conditions is poorly understood. In the current study, a 3D representative volume element (RVE) for cartilage tissue is created, comprising of a chondrocyte, surrounded by a pericellular matrix, and embedded in an extracellular matrix. A 3D active modelling framework incorporating actin cytoskeleton remodelling and contractility is implemented to predict the biomechanical behaviour of chondrocytes. Physiological and abnormal strain fields, based on the experimental study of Wong and Sah (Wong and Sah, J. Orthop. Res., 28:1554-61 (2010)), are applied to the RVE. Simulations demonstrate that the presence of a focal defect significantly affects cellular deformation, increases the stress experienced by the nucleus, and alters the distribution of the actin cytoskeleton. It is demonstrated that during dynamic loading, cyclic tension reduction in the cytoplasm causes continuous dissociation of the actin cytoskeleton. In contrast, during static loading significant changes in cytoplasm tension are not predicted and hence the rate of dissociation of the actin cytoskeleton is reduced. It is demonstrated that chondrocyte behaviour is affected by the stiffness of the pericellular matrix, and also by the anisotropy of the extracellular matrix. The findings of the current study are of particular importance for understanding the biomechanics underlying experimental observations such as actin cytoskeleton dissociation during the dynamic loading of chondrocytes.

Concepts: Extracellular matrix, Cartilage, Cytoskeleton, Biomechanics, Young's modulus, Osteoblast, Autologous chondrocyte implantation, Chondrocyte


Concomitant unloading procedures, such as high tibial osteotomy (HTO), are increasingly recognized as an important part of cartilage repair. This study presents survival rate, functional outcome, complication rate, and return to work following combined single-stage autologous chondrocyte implantation (ACI) and HTO.

Concepts: Cartilage, Orthopedic surgery, Knee cartilage replacement therapy, Osteotomy, Autologous chondrocyte implantation, Articular cartilage repair


Runx1, the hematopoietic lineage determining transcription factor, is present in perichondrium and chondrocytes. Here we addressed Runx1 functions, by examining expression in cartilage during mouse and human osteoarthritis (OA) progression and in response to mechanical loading.

Concepts: Gene, Gene expression, Transcription, Cartilage, Osteoarthritis, Transcription factor, Autologous chondrocyte implantation, Chondrocyte


Osteoarthritis (OA) is associated with a gradual reduction in the interstitial osmotic pressure within articular cartilage. The aim of this study was to compare the effects of sudden and gradual hypo-osmotic challenge on chondrocyte morphology and biomechanics.

Concepts: Bone, Chondroitin sulfate, Cartilage, Thermodynamics, Knee, Biomechanics, Autologous chondrocyte implantation, Chondrocyte


Articular cartilage is an avascular and aneural tissue with limited capacity for regeneration. On large articular lesions, it is recommended to use regenerative medicine strategies, like autologous chondrocyte implantation. There is a concern about morphological changes that chondrocytes suffer once they have been isolated and cultured. Due to the fact that there is little evidence that compares articular cartilage chondrocytes with cultured chondrocytes, in this research we proposed to obtain chondrocytes from human articular cartilage, compare them with themselves once they have been cultured and characterize them through genetic, phenotypic and morphological analysis. Knee articular cartilage samples of 10 mm were obtained, and each sample was divided into two fragments; a portion was used to determine gene expression, and from the other portion, chondrocytes were obtained by enzymatic disaggregation, in order to be cultured and expanded in vitro. Subsequently, morphological, genetic and phenotypic characteristics were compared between in situ (articular cartilage) and cultured chondrocytes. Obtained cultured chondrocytes were rounded in shape, possessing a large nucleus with condensed chromatin and a clear cytoplasm; histological appearance was quite similar to typical chondrocyte. The expression levels of COL2A1 and COL10A1 genes were higher in cultured chondrocytes than in situ chondrocytes; moreover, the expression of COL1A1 was almost undetectable on cultured chondrocytes; likewise, COL2 and SOX9 proteins were detected by immunofluorescence. We concluded that chondrocytes derived from adult human cartilage cultured for 21 days do not tend to dedifferentiate, maintaining their capacity to produce matrix and also retaining their synthesis capacity and morphology.

Concepts: DNA, Gene, Genetics, Cell nucleus, Gene expression, Cell, Cartilage, Autologous chondrocyte implantation


Chondral injuries are short of self-healing ability and need to surgical repair after articular cartilage injury. Conventional treatment includes debridement and drainage under arthroscope, micro-fracture, osteochondral autograft transplantation (OATS), mosaiplasty and osteochondral allografts (OCA), autologous chondrocyte implantation (ACI). Debridement and drainage could remove pain factor, and has advantages of simple operation, wide clinical application and early clinical effect. Micro-fracture and osteochondral autograft transplantation is suitable for small area of cartilage repair, while the further effect showed that fibrous cartilage permeated by drill could decrease postoperative clinical effect. Osteochondral autograft transplantation has better advantages for reconstruction complete of wear-bearing joint. Autologous chondrocyte implantation and allogeneic cartilage transplantation are suitable for large area of cartilage defect, postoperative survival of allogeneic cartilage transplantation is effected by local rejection reaction and decrease further clinical effect. Cartilage tissue engineering technology could improve repair quality of autologous chondrocyte implantation, and make repair tissue close to transparent cartilage, but has limit to combined subchondral bone plate, reactive bone edema, bone loss and bad axis of lower limb. New technology is applied to cartilage injury, and has advantages of less trauma, simple operation, rapid recover, good clinical effect and less cost;and could be main method for treat cartilage injury with surgical repair technology. How to improve repair quality with compression resistance and abrasive resistance are expected to be solved.

Concepts: Bone, Extracellular matrix, Cartilage, Knee, Organ transplant, Knee cartilage replacement therapy, Autologous chondrocyte implantation, Articular cartilage repair


Osteoarthritis (OA) is a major cause of disability and morbidity in the aging population. Joint injury leads to cartilage damage, a known determinant for subsequent development of posttraumatic OA, which accounts for 12% of all OA. Understanding the early molecular and cellular responses postinjury may provide targets for therapeutic interventions that limit articular degeneration. Using a murine model of controlled knee joint impact injury that allows the examination of cartilage responses to injury at specific time points, we show that intraarticular delivery of a peptidic nanoparticle complexed to NF-κB siRNA significantly reduces early chondrocyte apoptosis and reactive synovitis. Our data suggest that NF-κB siRNA nanotherapy maintains cartilage homeostasis by enhancing AMPK signaling while suppressing mTORC1 and Wnt/β-catenin activity. These findings delineate an extensive crosstalk between NF-κB and signaling pathways that govern cartilage responses postinjury and suggest that delivery of NF-κB siRNA nanotherapy to attenuate early inflammation may limit the chronic consequences of joint injury. Therapeutic benefits of siRNA nanotherapy may also apply to primary OA in which NF-κB activation mediates chondrocyte catabolic responses. Additionally, a critical barrier to the successful development of OA treatment includes ineffective delivery of therapeutic agents to the resident chondrocytes in the avascular cartilage. Here, we show that the peptide-siRNA nanocomplexes are nonimmunogenic, are freely and deeply penetrant to human OA cartilage, and persist in chondrocyte lacunae for at least 2 wk. The peptide-siRNA platform thus provides a clinically relevant and promising approach to overcoming the obstacles of drug delivery to the highly inaccessible chondrocytes.

Concepts: Bone, Signal transduction, Cartilage, Osteoarthritis, Knee, Joint, Autologous chondrocyte implantation, Chondrocyte


Descriptive epidemiology of total joint replacement procedures is limited to annual procedure volumes (incidence). The prevalence of the growing number of individuals living with a total hip or total knee replacement is currently unknown. Our objective was to estimate the prevalence of total hip and total knee replacement in the United States.

Concepts: Epidemiology, United States, Incidence, Osteoarthritis, Orthopedic surgery, Joints, Knee replacement, Autologous chondrocyte implantation


In embryonic models and stem cell systems, mesenchymal cells derived from the neuroectoderm can be distinguished from mesoderm-derived cells by their Hox-negative profile-a phenotype associated with enhanced capacity of tissue regeneration. We investigated whether developmental origin and Hox negativity correlated with self-renewal and environmental plasticity also in differentiated cells from adults. Using hyaline cartilage as a model, we showed that adult human neuroectoderm-derived nasal chondrocytes (NCs) can be constitutively distinguished from mesoderm-derived articular chondrocytes (ACs) by lack of expression of specific HOX genes, including HOXC4 and HOXD8. In contrast to ACs, serially cloned NCs could be continuously reverted from differentiated to dedifferentiated states, conserving the ability to form cartilage tissue in vitro and in vivo. NCs could also be reprogrammed to stably express Hox genes typical of ACs upon implantation into goat articular cartilage defects, directly contributing to cartilage repair. Our findings identify previously unrecognized regenerative properties of HOX-negative differentiated neuroectoderm cells in adults, implying a role for NCs in the unmet clinical challenge of articular cartilage repair. An ongoing phase 1 clinical trial preliminarily indicated the safety and feasibility of autologous NC-based engineered tissues for the treatment of traumatic articular cartilage lesions.

Concepts: Gene, Developmental biology, Cellular differentiation, Cartilage, Tissues, Mesenchyme, Autologous chondrocyte implantation, Articular cartilage repair