Engineering Anisotropic Meniscus: Zonal Functionality and Spatiotemporal Drug Delivery.

Human meniscus is a fibrocartilaginous structure that is crucial for an adequate performance of the human knee joint. Degeneration of the meniscus is often followed by partial or total meniscectomy, which enhances the risk of developing knee osteoarthritis. The lack of a satisfactory treatment for this condition has triggered a major interest in drug delivery (DD) and tissue engineering (TE) strategies intended to restore a bioactive and fully functional meniscal tissue. The aim of this review is to critically discuss the most relevant studies on spatiotemporal DD and TE, aiming for a multizonal meniscal reconstruction. Indeed, the development of meniscal tissue implants should involve a provision for adequate active molecules and scaffold features that take into account the anisotropic ultrastructure of human meniscus. This zonal differentiation is reflected in the meniscus biochemical composition, collagen fiber arrangement, and cell distribution. In this sense, it is expected that a proper combination of advanced DD and zonal TE strategies will play a key role in the future trends in meniscus regeneration. Impact statement Meniscus degeneration is one of the main causes of knee pain, inflammation, and reduced mobility. Currently used suturing procedures and meniscectomy are far from being ideal solutions to the loss of meniscal function. Therefore, drug delivery (DD) and tissue engineering (TE) strategies are currently under investigation. DD systems aim at an controlled release of growth factors, whereas TE strategies aim at mimicking the anisotropy of native meniscus. The goal of this review is to discuss these two main approaches, as well as synergies between them that are expected to lead to a real breakthrough in the field.