Bioprinting is a process based on additive manufacturing from materials containing living cells. These materials, often referred to as bioink, are based on cytocompatible hydrogel precursor formulations, which gel in a manner compatible with different bioprinting approaches. The bioink properties before, during and after gelation are essential for its printability, comprising such features as achievable structural resolution, shape fidelity and cell survival. However, it is the final properties of the matured bioprinted tissue construct that are crucial for the end application. During tissue formation these properties are influenced by the amount of cells present in the construct, their proliferation, migration and interaction with the material. A calibrated computational framework is able to predict the tissue development and maturation and to optimize the bioprinting input parameters such as the starting material, the initial cell loading and the construct geometry. In this contribution relevant bioink properties are reviewed and discussed on the example of most popular bioprinting approaches. The effect of cells on hydrogel processing and vice versa is highlighted. Furthermore, numerical approaches were reviewed and implemented for depicting the cellular mechanics within the hydrogel as well as for prediction of mechanical properties to achieve the desired hydrogel construct considering cell density, distribution and material-cell interaction.

Three-dimensional (3D) printing is a promising technology to develop customized biomaterials in regenerative medicine. However, for the majority of printable biomaterials (bioinks) there is always a compromise between excellent printability of fluids and good mechanical properties of solids. Three-dimensional printing of soft materials based on the transition from a fluid to gel state is challenging because of the difficulties to control such transition as well as to maintain uniform conditions three-dimensionally. To solve these challenges, a facile chemical strategy for the development of a novel hydrogel bioink with shear-thinning and self-healing properties based on dynamic metal–ligand coordination bonds is presented. The noncovalent cross-linking allows easy extrusion of the bioink from a reservoir without changing of its bulk mechanical properties. The soft hydrogel can avoid deformation and collapse using omnidirectional embedding of the printable hydrogel into a support gel bath sharing the same cross-linking chemistry. After combination with photoinitiated covalent cross-linking, it enables manufacturing of hydrogel structures with complex shapes and precise location of chemically attached ligands. Living cells can be entrapped in the new printable hydrogel and survive the following in situ photo-cross-linking. The presented printable hydrogel material expands the existing tool-box of bioinks for generation of in vitro 3D tissue-like structures and direct in vivo 3D printing.

Three-dimensional (3D) printing offers versatile possibilities for adapting the structural parameters of tissue engineering scaffolds. However, it is also essential to develop procedures allowing efficient cell seeding independent of scaffold geometry and pore size. The aim of this study was to establish a method for seeding the scaffolds using photopolymerizable cell-laden hydrogels. The latter facilitates convenient preparation, and handling of cell suspension, while distributing the hydrogel precursor throughout the pores, before it is cross-linked with light. In addition, encapsulation of living cells within hydrogels can produce constructs with high initial cell loading and intimate cell-matrix contact, similar to that of the natural extra-cellular matrix (ECM). Three dimensional scaffolds were produced from poly(lactic) acid (PLA) by means of fused deposition modeling. A solution of methacrylamide-modified gelatin (Gel-MOD) in cell culture medium containing photoinitiator Li-TPO-L was used as a hydrogel precursor. Being an enzymatically degradable derivative of natural collagen, gelatin-based matrices are biomimetic and potentially support the process of cell-induced remodeling. Preosteoblast cells MC3T3-E1 at a density of 10 × 10 cells per 1 mL were used for testing the seeding procedure and cell proliferation studies. Obtained results indicate that produced constructs support cell survival and proliferation over extended duration of our experiment. The established two-step approach for scaffold seeding with the cells is simple, rapid, and is shown to be highly reproducible. Furthermore, it enables precise control of the initial cell density, while yielding their uniform distribution throughout the scaffold. Such hybrid tissue engineering constructs merge the advantages of rigid 3D printed constructs with the soft hydrogel matrix, potentially mimicking the process of ECM remodeling.