‘Additive manufacturing’ (AM) refers to a class of manufacturing processes based on the building of a solid object from three‐dimensional (3D) model data by joining materials, usually layer upon layer. Among the vast array of techniques developed for the production of tissue‐engineering (TE) scaffolds, AM techniques are gaining great interest for their suitability in achieving complex shapes and microstructures with a high degree of automation, good accuracy and reproducibility. In addition, the possibility of rapidly producing tissue‐engineered constructs meeting patient's specific requirements, in terms of tissue defect size and geometry as well as autologous biological features, makes them a powerful way of enhancing clinical routine procedures. This paper gives an extensive overview of different AM techniques classes (i.e. stereolithography, selective laser sintering, 3D printing, melt–extrusion‐based techniques, solution/slurry extrusion‐based techniques, and tissue and organ printing) employed for the development of tissue‐engineered constructs made of different materials (i.e. polymeric, ceramic and composite, alone or in combination with bioactive agents), by highlighting their principles and technological solutions. Copyright © 2012 John Wiley & Sons, Ltd.

Bioprinting techniques have been flourishing in the field of biofabrication with pronounced and exponential developments in the past years. Novel biomaterial inks used for the formation of bioinks have been developed, allowing the manufacturing of in vitro models and implants tested preclinically with a certain degree of success. Furthermore, incredible advances in cell biology, namely, in pluripotent stem cells, have also contributed to the latest milestones where more relevant tissues or organ-like constructs with a certain degree of functionality can already be obtained. These incredible strides have been possible with a multitude of multidisciplinary teams around the world, working to make bioprinted tissues and organs more relevant and functional. Yet, there is still a long way to go until these biofabricated constructs will be able to reach the clinics. In this review, we summarize the main bioprinting activities linking them to tissue and organ development and physiology. Most bioprinting approaches focus on mimicking fully matured tissues. Future bioprinting strategies might pursue earlier developmental stages of tissues and organs. The continuous convergence of the experts in the fields of material sciences, cell biology, engineering, and many other disciplines will gradually allow us to overcome the barriers identified on the demanding path toward manufacturing and adoption of tissue and organ replacements.

Bioprinting is a powerful technique that allows precise and controlled 3D deposition of biomaterials in a predesigned, customizable, and reproducible manner. Cell-laden hydrogel (“bioink”) bioprinting is especially advantageous for tissue engineering applications as multiple cells and biomaterial compositions can be selectively dispensed to create spatially well-defined architectures. Despite this promise, few hydrogel systems are easily available and suitable as bioinks, with even fewer systems allowing for molecular design of mechanical and biological properties. In this study, we report the development of a norbornene functionalized alginate system as a cell-laden bioink for extrusion-based bioprinting, with a rapid UV-induced thiol-ene crosslinking mechanism that avoids acrylate kinetic chain formation. The mechanical and swelling properties of the hydrogels are tunable by varying the concentration, length, and structure of di-thiol PEG cross-linkers, and can be further modified by post-printing secondary crosslinking with divalent ions such as calcium. The low concentrations of alginate needed (<2 wt%), coupled with their rapid in situ gelation, allows both the maintenance of high cell viability and the ability to fabricate large multi-layer or multi-bioink constructs with identical bioprinting conditions. The modularity of this bioink platform design not only enables the rational design of materials properties, but also the gel’s biofunctionality (as shown via RGD attachment) for the expected tissue-engineering application. This modularity enables the creation of multi-zonal and multi-cellular constructs utilizing a chemically similar bioink platform. Such tailorable bioink platforms will enable increased complexity in 3D bioprinted constructs.

Despite the great advances that the tissue engineering field has experienced over the last two decades, the amount of in vitro engineered tissues that have reached a stage of clinical trial is limited. While many challenges are still to be overcome, the lack of vascularization represents a major milestone if tissues bigger than approximately 200 µm are to be transplanted. Cell survival and homeostasis is to a large extent conditioned by the oxygen and nutrient transport (as well as waste removal) by blood vessels on their proximity and spontaneous vascularization in vivo is a relatively slow process, leading all together to necrosis of implanted tissues. Thus, in vitro vascularization appears to be a requirement for the advancement of the field. One of the main approaches to this end is the formation of vascular templates that will develop in vitro together with the targeted engineered tissue. Bioprinting, a fast and reliable method for the deposition of cells and materials on a precise manner, appears as an excellent fabrication technique. In this review, we provide a comprehensive background to the fields of vascularization and bioprinting, providing details on the current strategies, cell sources, materials and outcomes of these studies.