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Three dimensional (3D) bioprinting has been a powerful tool in patterning and precisely placing biologics, including living cells, nucleic acids, drug particles, proteins and growth factors, to recapitulate tissue anatomy, biology and physiology. Since the first time of cytoscribing cells demonstrated in 1986, bioprinting has made a substantial leap forward, particularly in the past 10 years, and it has been widely used in fabrication of living tissues for various application areas. The technology has been recently commercialized by several emerging businesses, and bioprinters and bioprinted tissues have gained significant interest in medicine and pharmaceutics. This Keynote review presents the bioprinting technology and covers a first-time comprehensive overview of its application areas from tissue engineering and regenerative medicine to pharmaceutics and cancer research.

Despite extensive use of polydimethylsiloxane (PDMS) in medical applications, such as lab-on-a-chip or tissue/organ-on-a-chip devices, point-of-care devices, and biological machines, the manufacturing of PDMS devices is limited to soft-lithography and its derivatives, which prohibits the fabrication of geometrically complex shapes. With the recent advances in three-dimensional (3D) printing, use of PDMS for fabrication of such complex shapes has gained considerable interest. This research presents a detailed investigation on printability of PDMS elastomers over three concentrations for mechanical and cell adhesion studies. The results demonstrate that 3D printing of PDMS improved the mechanical properties of fabricated samples up to three fold compared to that of cast ones because of the decreased porosity of bubble entrapment. Most importantly, 3D printing facilitates the adhesion of breast cancer cells, whereas cast samples do not allow cellular adhesion without the use of additional coatings such as extracellular matrix proteins. Cells are able to adhere and grow in the grooves along the printed filaments demonstrating that 3D printed devices can be engineered with superior cell adhesion qualities compared to traditionally manufactured PDMS devices.

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Extrusion-based bioprinting of hydrogels in a granular secondary gel enables the fabrication of cell-laden three-dimensional (3D) constructs in an anatomically accurate manner, which is challenging using conventional extrusion-based bioprinting processes. In this study, carbohydrazide-modified gelatin (Gel-CDH) was synthesized and deposited into a new multifunctional support bath consisting of gelatin microparticles suspended in an oxidized alginate (OAlg) solution. During extrusion, Gel-CDH and OAlg were rapidly cross-linked because of the Schiff base formation between aldehyde groups of OAlg and amino groups of Gel-CDH, which has not been demonstrated in the domain of 3D bioprinting before. Rheological results indicated that hydrogels with lower OAlg to Gel-CDH ratios possessed superior mechanical rigidity. Different 3D geometrically intricate constructs were successfully created upon the determination of optimal bioprinting parameters. Human mesenchymal stem cells and human umbilical vein endothelial cells were also bioprinted at physiologically relevant cell densities. The presented study has offered a novel strategy for bioprinting of natural polymer-based hydrogels into 3D complex-shaped biomimetic constructs, which eliminated the need for cytotoxic supplements as external cross-linkers or additional cross-linking processes, therefore expanding the availability of bioinks.