There has been considerable advancement over the last few years in the treatment of osteoarthritis, common chronic disease and a major cause of disability in older adults. In this pathology, the entire joint is involved and the regeneration of articular cartilage still remains one of the main challenges, particularly in an actively inflammatory environment. The recent strategies for osteoarthritis treatment are based on the use of different therapeutic solutions such as cell and gene therapies and tissue engineering. In this review, we provide an overview of current regenerative strategies highlighting the pros and cons, challenges and opportunities, and we try to identify areas where future work should be focused in order to advance this field.

Cartilage lesions fail to heal spontaneously, leading to the development of chronic conditions which worsen the life quality of patients. Three-dimensional scaffold-based bioprinting holds the potential of tissue regeneration through the creation of organized, living constructs via a “layer-by-layer” deposition of small units of biomaterials and cells. This technique displays important advantages to mimic natural cartilage over traditional methods by allowing a fine control of cell distribution, and the modulation of mechanical and chemical properties. This opens up a number of new perspectives including personalized medicine through the development of complex structures (the osteochondral compartment), different types of cartilage (hyaline, fibrous), and constructs according to a specific patient’s needs. However, the choice of the ideal combination of biomaterials and cells for cartilage bioprinting is still a challenge. Stem cells may improve material mimicry ability thanks to their unique properties: the immune-privileged status and the paracrine activity. Here, we review the recent advances in cartilage three-dimensional, scaffold-based bioprinting using stem cells and identify future developments for clinical translation. Database search terms used to write this review were: “articular cartilage”, “menisci”, “3D bioprinting”, “bioinks”, “stem cells”, and “cartilage tissue engineering”.

Excessive bone resorption by osteoclasts (OCs) covers an essential role in developing bone diseases, such as osteoporosis (OP) and rheumatoid arthritis (RA). Monocytes or macrophages fusion and multinucleation (M-FM) are key processes for generating multinucleated mature cells with essential roles in bone remodelling. Depending on the phenotypic heterogeneity of monocyte/macrophage precursors and the extracellular milieu, two distinct morphological and functional cell types can arise mature OCs and giant cells (GCs). Despite their biological relevance in several physiological and pathological responses, many gaps exist in our understanding of their formation and role in bone, including the molecular determinants of cell fusion and multinucleation. Here, we outline fusogenic molecules during M-FM involved in OCs and GCs formation in healthy conditions and during OP and RA. Moreover, we discuss the impact of the inflammatory milieu on modulating macrophages phenotype and their differentiation towards mature cells. Methodological approach envisaged searches on Scopus, Web of Science Core Collection, and EMBASE databases to select relevant studies on M-FM, osteoclastogenesis, inflammation, OP, and RA. This review intends to give a state-of-the-art description of mechanisms beyond osteoclastogenesis and M-FM, with a focus on OP and RA, and to highlight potential biological therapeutic targets to prevent extreme bone loss.