Meniscus regeneration is an unsolved clinical challenge. Despite the wide acceptance of the degenerative consequences of meniscectomy, no surgical procedure has succeeded to date in regenerating a functional and long-lasting meniscal fibrocartilage. Research proposed a number of experimental approaches encompassing all the typical strategies of regenerative medicine: cellfree scaffolds, gene therapy, intra-articular delivery of progenitor cells, biological glues for enhanced bonding of reparable tears, partial and total tissue engineered meniscus replacement. None of these approaches has been completely successful and can be considered suitable for all patients, as meniscal tears require specific and patientrelated treatments depending on the size and type of lesion. Recent advances in cell biology, biomaterial science and bioengineering (e.g., bioreactors) have now the potential to drive meniscus regeneration into a series of clinically relevant strategies. In this tutorial paper, the clinical need for meniscus regeneration strategies will be explained, and past and current experimental studies on meniscus regeneration will be reported.

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A large-deflection elasticity model was used to describe the mechanical behavior of cartilaginous tissues during three-point bending tests. Force-deflection curves were measured for 20-mm long x 4-mm wide x approximately 1-mm thick strips of porcine auricular and costal cartilage. Using a least-squares method with elastic modulus in bending as the only adjustable parameter, data were fit to a model based on the von Karman theory for large deflection of plates. This model described the data well, with an average RMS error of 14.8% and an average R(2) value of 0.98. Using this method, the bending modulus of auricular cartilage (4.6 MPa) was found to be statistically lower (p < 0.05) than that of costal cartilage (7.1 MPa). Material features of the cartilage samples influenced the mechanical behavior, including the orientation of the perichondrium in auricular cartilage. These methods also were used to determine the elastic moduli of engineered cartilage samples produced by seeding chondrocytes into fibrin glue. The modulus of tissue-engineered constructs increased statistically with time (p < 0.05), but still were statistically lower than the moduli of the native tissue samples (p > 0.05), reaching only about a third of the values of native samples.

This study evaluated the biomechanical characteristics of newly formed cartilaginous tissue synthesized from isolated chondrocytes and seeded onto devitalized cartilage in an extended study in vivo. Cartilage from porcine articular joints was cut into regular discs and devitalized by multiple freeze-thaw cycles. Articular chondrocytes were enzymatically isolated and incubated in suspension culture in the presence of devitalized cartilage discs for 21 days. This procedure allowed the isolated chondrocytes to adhere to the devitalized matrix surfaces. Chondrocyte-matrix constructs were assembled with fibrin glue and implanted in dorsal subcutaneous pockets in nude mice for up to 8 months. Histological evaluation and biomechanical testing were performed to quantify the integration of cartilage pieces and the mechanical properties of the constructs over time. Histological analysis indicated that chondrocytes grown on devitalized cartilage discs produced new matrix that bonded and integrated individual cartilage elements with mechanically functional tissue. Biomechanical testing demonstrated a time dependent increase in tensile strength, failure strain, failure energy, and tensile modulus to values 5-30% of normal articular cartilage by 8 months in vivo. The values recorded at 4 months were not statistically different from those collected at the latest time point, indicating that the limits of the biomechanical property values were reached after four months from implantation.

We propose a culture-free approach to osteochondral repair with minced autologous cartilage fragments loaded onto a scaffold composed of a hyaluronic acid (HA)-derived membrane, platelet-rich fibrin matrix (PRFM) and fibrin glue. The aim of the study was to demonstrate in vitro

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