Title: The progression of 3D-printed tissue engineering strategies for heterogeneous meniscus reconstruction

Abstract

The meniscus is the fibrocartilage tissue of the knee joint, which plays an important role in transmitting loads, shock absorption, maintaining joint stability and reducing contact stress. Meniscal injuries can be commonly treated with simple sutures, while meniscectomy is inevitably required for severe injuries. However, meniscectomy could disrupt the mechanical microenvironment of the knee joint, leading to articular cartilage degeneration and osteoarthritis (OA). Tissue engineering technology, as a strategy with diverse origins, customizable and tunable mechanical and biological properties, has emerged as a promising approach for the treatment of meniscal injuries represented by 3D printing. Notably, the heterogeneity of the meniscus, including anatomical structure, cellular phenotype, extracellular matrix (ECM), and biomechanical properties, is critical for the reconstruction of natural bio-function. Therefore, the construction of heterogeneous tissue-engineered meniscus has become a promising approach for meniscus substitution and regeneration. Hereby, we systematically summarized the heterogeneity of the meniscus and 3D printing strategies for tissue engineering anisotropic meniscus. Manufacturing techniques, biomaterial combinations, surface functionalization, growth factors, and bioreactors related to 3D printing strategies are highlighted, and future research directions are proposed.