A guide to articular cartilage functioning: a comprehensive review, current challenges and mechanobiological solutions

Articular cartilage exhibits a remarkable mechanical and biological performance, which allows it to withstand high stresses and strains with minimal deformation, lasting decades of continuous use without failure. Upon damage, its self-repair is naturally difficult, being its regeneration a serious challenge today with current therapies failing in restoring the natural environment of this tissue. The present review delves deeply into the biomechanical functioning of articular cartilage, giving special attention to the interplay between its structure and composition with its mechanical behaviour at both tissue and cellular levels. The mechanisms by which articular cartilage responds to injury are highlighted to comprehend how this tissue is naturally damaged and how it could be regenerated, considering its native functioning. The current options for clinical evaluation and treatment are summarized. Drawing inspiration from the natural environment of articular cartilage and the mechanisms responsible for its health homeostasis, the application of optical and acoustic stimulation is proposed as mechanobiological solutions for promoting cartilage regeneration, followed by a final discussion on its current challenges and future perspectives. This review highlights the articular cartilage mechanical and biological functioning at both tissue and cellular level, elucidating strategies and challenges of articular cartilage regeneration in clinical research.