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Objective: To develop a new macroscopic scoring system which allows for an overall judgment of experimental articular cartilage repair and compare it with four existing scoring systems and high-field magnetic resonance imaging (MRI).Methods: A new macroscopic scoring system was developed to assess the repair of cartilage defects. Cartilage repair was graded by three observers with different experience in cartilage research at 2-3 time points and compared with the protocol A of the international cartilage repair society (ICRS) cartilage repair assessment score, the Oswestry arthroscopy score, and macroscopic grading systems designed by Jung and O'Driscoll. Parameters were correlated with the two-dimensional (2D) magnetic resonance observation of cartilage repair tissue (MOCART) score based on a 9.4 T MRI as an external reference standard.Results: All macroscopic scores exhibited high intra- and interobserver reliability and high internal correlation. The newly developed macroscopic scoring system had the highest intraobserver [0.866 ≤ intraclass correlation (ICC) ≤ 0.895] and the highest interobserver reliability (ICC = 0.905) for "total points". Here, Cronbach's alpha indicated good homogeneity and functioning of the items (mean = 0.782). "Total points" of the 2D MOCART score correlated with all macroscopic scores (all P < 0.0001). The newly developed macroscopic scoring system yielded the highest correlation for the MRI parameter "defect fill" (rho = 0.765; all P < 0.0001).Conclusions: "Total points" and "defect fill", two clinically relevant indicators of cartilage repair, can be reliably and directly assessed by macroscopic evaluation, using either system. These data support the use of macroscopic assessment to precisely judge cartilage repair in preclinical large animal models. [ABSTRACT FROM AUTHOR]

Meniscal lesions are common problems in orthopaedic surgery and sports medicine, and injury or loss of the meniscus accelerates the onset of knee osteoarthritis (OA). Despite a variety of therapeutic options in the clinics, there is a critical need for improved treatments to enhance meniscal repair. In this regard, combining gene-, cell-, and tissue engineering-based approaches is an attractive strategy to generate novel, effective therapies to treat meniscal lesions. In the present work, we provide an overview of the tools currently available to improve meniscal repair and discuss the progress and remaining challenges for potential future translation in patients. [ABSTRACT FROM AUTHOR]

Objectives: Current repair procedures for articular cartilage (AC) cannot restore the tissue's original form and function because neither changes in its architectural blueprint throughout life nor the respective biological understanding is fully available. We asked whether two unique elements of human cartilage architecture, the chondrocyte-surrounding pericellular matrix (PCM) and the superficial chondrocyte spatial organization (SCSO) beneath the articular surface (AS) are congenital, stable or dynamic throughout life. We hypothesized that inducing chondrocyte proliferation in vitro impairs organization and PCM and induces an advanced osteoarthritis (OA)-like structural phenotype of human cartilage.Methods: We recorded propidium-iodine-stained fetal and adult cartilage explants, arranged stages of organization into a sequence, and created a lifetime-summarizing SCSO model. To replicate the OA-associated dynamics revealed by our model, and to test our hypothesis, we transduced specifically early OA-explants with hFGF-2 for inducing proliferation. The PCM was examined using immuno- and auto-fluorescence, multiphoton second-harmonic-generation (SHG), and scanning electron microscopy (SEM).Results: Spatial organization evolved from fetal homogeneity, peaked with adult string-like arrangements, but was completely lost in OA. Loss of organization included PCM perforation (local micro-fibrillar collagen intensity decrease) and destruction [regional collagen type VI (CollVI) signal weakness or absence]. Importantly, both loss of organization and PCM destruction were successfully recapitulated in FGF-2-transduced explants.Conclusion: Induced proliferation of spatially characterized early OA-chondrocytes within standardized explants recapitulated the full range of loss of SCSO and PCM destruction, introducing a novel in vitro methodology. This methodology induces a structural phenotype of human cartilage that is similar to advanced OA and potentially of significance and utility. [ABSTRACT FROM AUTHOR]

The genetic modification of freshly aspirated bone marrow may provide convenient tools to enhance the regenerative capacities of cartilage defects compared with the complex manipulation of isolated progenitor cells. In the present study, we examined the ability and safety of recombinant adeno-associated virus (rAAV) serotype 2 vectors to deliver various reporter gene sequences in primary human bone marrow aspirates over time without altering the chondrogenic processes in the samples. The results demonstrate that successful rAAV-mediated gene transfer and expression of the lacZ and red fluorescent protein marker genes were achieved in transduced aspirates at very high efficiencies (90-94%) and over extended periods of time (up to 125 days) upon treatment with hirudin, an alternative anticoagulant that does not prevent the adsorption of the rAAV-2 particles at the surface of their targets compared with heparin. Application of rAAV was safe, displaying neither cytotoxic nor detrimental effects on the cellular and proliferative activities or on the chondrogenic processes in the aspirates especially using an optimal dose of 0.5 mg ml−1 hirudin, and application of the potent SOX9 transcription factor even enhanced these processes while counteracting hypertrophic differentiation. The current findings demonstrate the clinical value of this class of vector to durably and safely modify bone marrow aspirates as a means to further develop convenient therapeutic approaches to improve the healing of cartilage defects. [ABSTRACT FROM AUTHOR]