Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss current clinical approaches for repairing cartilage, as well as research approaches which are currently developing, and those under translation into clinical practice. We also describe potential future directions in this area, including tissue engineering based on scaffolding and/or stem cells as well as a combination of gene and cell therapy. Particular focus is placed on cell-based approaches and the potential of recently characterized chondro-progenitors; progress with induced pluripotent stem cells is also discussed. In this context, we also consider the ability of different types of stem cell to restore hyaline cartilage and the importance of mimicking the environment in vivo during cell expansion and differentiation into mature chondrocytes.

Osteoarthritis (OA) is a common degenerative joint disease treated mostly symptomatically before approaching its definitive treatment, joint arthroplasty. The rapidly growing prevalence of OA highlights the urgent need for a more efficient treatment strategy and boosts research into the mechanisms of OA incidence and progression. As a multifactorial disease, many aspects have been investigated as contributors to OA onset and progression. Differences in gender appear to play a role in the natural history of the disease, since female sex is known to increase the susceptibility to its development. The aim of the present review is to investigate the cues associated with gender by analyzing various hormonal, anatomical, molecular, and biomechanical parameters, as well as their differences between sexes. Our findings reveal the possible implications of gender in OA onset and progression and provide evidence for gaps in the current state of art, thus suggesting future research directions.

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Osteoarthritis (OA) affects over 250 million people worldwide and despite various existing treatment strategies still has no cure. It is a multifactorial disease characterized by cartilage loss and low-grade synovial inflammation. Focusing on these two targets together could be the key to developing currently missing disease-modifying OA drugs (DMOADs). This review aims to discuss the latest cell-free techniques applied in cartilage tissue regeneration, since they can provide a more controllable approach to inflammation management than the cell-based ones. Scaffolds, extracellular vesicles, and nanocarriers can be used to suppress inflammation, but they can also act as immunomodulatory agents. This is consistent with the latest tissue engineering paradigm, postulating a moderate, controllable inflammatory reaction to be beneficial for tissue remodeling and successful regeneration.