Abbadessa, AnnaRonca, AlfredoSalerno, Aurelio2024-03-062024-03-0620232190-393Xhttp://hdl.handle.net/10347/33029The biological and biomechanical functions of cartilage, bone and osteochondral tissue are naturally orchestrated by a complex crosstalk between zonally dependent cells and extracellular matrix components. In fact, this crosstalk involves biomechanical signals and the release of biochemical cues that direct cell fate and regulate tissue morphogenesis and remodelling in vivo. Three-dimensional bioprinting introduced a paradigm shift in tissue engineering and regenerative medicine, since it allows to mimic native tissue anisotropy introducing compositional and architectural gradients. Moreover, the growing synergy between bioprinting and drug delivery may enable to replicate cell/extracellular matrix reciprocity and dynamics by the careful control of the spatial and temporal patterning of bioactive cues. Although significant advances have been made in this direction, unmet challenges and open research questions persist. These include, among others, the optimization of scaffold zonality and architectural features; the preservation of the bioactivity of loaded active molecules, as well as their spatio-temporal release; the in vitro scaffold maturation prior to implantation; the pros and cons of each animal model and the graft-defect mismatch; and the in vivo non-invasive monitoring of new tissue formation. This work critically reviews these aspects and reveals the state of the art of using three-dimensional bioprinting, and its synergy with drug delivery technologies, to pattern the distribution of cells and/or active molecules in cartilage, bone and osteochondral engineered tissues. Most notably, this work focuses on approaches, technologies and biomaterials that are currently under in vivo investigations, as these give important insights on scaffold performance at the implantation site and its interaction/integration with surrounding tissueseng© 2023. The Author(s).Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Bioprinted scafolds Bone Cartilage Osteochondral tissue Growth factors Spatio-temporal drug releasejournal article10.1007/s13346-023-01437-12190-3948open access