Strategies to engineer articular cartilage with biomimetic zonal features: a review

Articular cartilage (AC) is a highly specialized tissue with restricted ability for self-regeneration, given its avascular and acellular nature. Although a considerable number of surgical treatments is available for the repair, reconstruction, and regeneration of AC defects, most of them do not prioritize the development of engineered cartilage with zonal stratification derived from biomimetic biochemical, biomechanical and topographic cues. In the absence of these zonal elements, engineered cartilage will exhibit increased susceptibility to failure and will neither be able to withstand the mechanical loading to which AC is subjected nor will it integrate well with the surrounding tissue. In this regard, new breakthroughs in the development of hierarchical stratified engineered cartilage are highly sought after. Initially, this review provides a comprehensive analysis of the composition and zonal organization of AC, aiming to enhance our understanding of the significance of the structure of AC for its function. Next, we direct our attention towards the existing in vitro and in vivo studies that introduce zonal elements in engineered cartilage to elicit appropriate AC regeneration by employing tissue engineering strategies. Finally, the advantages, challenges, and future perspectives of these approaches are presented.