BackgroundThe worldwide demand for the organ replacement or tissue regeneration is increasing steadily. The advancements in tissue engineering and regenerative medicine have made it possible to regenerate such damaged organs or tissues into functional organ or tissue with the help of 3D bioprinting. The main component of the 3D bioprinting is the bioink, which is crucial for the development of functional organs or tissue structures. The bioinks used in 3D printing technology require so many properties which are vital and need to be considered during the selection. Combination of different methods and enhancements in properties are required to develop more successful bioinks for the 3D printing of organs or tissue structures.Main bodyThis review consists of the recent state-of-art of polymer-based bioinks used in 3D printing for applications in tissue engineering and regenerative medicine. The subsection projects the basic requirements for the selection of successful bioinks for 3D printing and developing 3D tissues or organ structures using combinations of bioinks such as cells, biomedical polymers and biosignals. Different bioink materials and their properties related to the biocompatibility, printability, mechanical properties, which are recently reported for 3D printing are discussed in detail.ConclusionMany bioinks formulations have been reported from cell-biomaterials based bioinks to cell-based bioinks such as cell aggregates and tissue spheroids for tissue engineering and regenerative medicine applications. Interestingly, more tunable bioinks, which are biocompatible for live cells, printable and mechanically stable after printing are emerging with the help of functional polymeric biomaterials, their modifications and blending of cells and hydrogels. These approaches show the immense potential of these bioinks to produce more complex tissue/organ structures using 3D bioprinting in the future.

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Osteochondral defects cannot be adequately self-repaired due to the presence of the sophisticated hierarchical structure and the lack of blood supply in cartilage. Thus, one of the major challenges remaining in this field is the structural design of a biomimetic scaffold that satisfies the specific requirements for osteochondral repair. To address this hurdle, a bio-inspired multilayer osteochondral scaffold that consisted of the poly(ε-caprolactone) (PCL) and the hydroxyapatite (HA)/PCL microspheres, was constructed via selective laser sintering (SLS) technique. The SLS-derived scaffolds exhibited an excellent biocompatibility to support cell adhesion and proliferation in vitro. The repair effect was evaluated by implanting the acellular multilayer scaffolds into osteochondral defects of a rabbit model. Our findings demonstrated that the multilayer scaffolds were able to induce articular cartilage formation by accelerating the early subchondral bone regeneration, and the newly formed tissues could well integrate with the native tissues. Consequently, the current study not only achieves osteochondral repair, but also suggests a promising strategy for the fabrication of bio-inspired multilayer scaffolds with well-designed architecture and gradient composition via SLS technique.

BackgroundAfter recognition of 3D printing and injectable hydrogel as a critical issue in tissue/organ engineering and regenerative medicine society, many hydrogels as bioinks have been developed worldwide by using polymeric biomaterials such as gelatin, alginate, hyaluronic acid and others. Even though some gels have shown good performances in 3D bioprinting, still their performances do not meet the requirements enough to be used as a bioink in tissue engineering.MethodIn this study, a hydrogel consisting of three biocompatible biomaterials such as hyaluronic acid (HA), hydroxyethyl acrylate (HEA) and gelatin-methacryloyl, i.e. HA-g-pHEA-gelatin gel, has been evaluated for its possibility as a bioprinting gel, a bioink. Hydrogel synthesis was obtained by graft polymerization of HEA to HA and then grafting of gelatin- methacryloyl via radical polymerization mechanism. Physical and biological properties of the HA-based hydrogels fabricated with different concentrations of methacrylic anhydride (6 and 8%) for gelatin-methacryloylation have been evaluated such as swelling, rheology, morphology, cell compatibility, and delivery of small molecular dimethyloxalylglycine. Printings of HA-g-pHEA-Gelatin gel and its bioink with bone cell loaded in lattice forms were also evaluated by using home-built multi-material (3D bio-) printing system.ConclusionThe experimental results demonstrated that the HA-g-pHEA-gelatin hydrogel showed both stable rheology properties and excellent biocompatibility, and the gel showed printability in good shape. The bone cells in bioinks of the lattice-printed scaffolds were viable. This study showed HA-g-pHEA-Gelatin gel’s potential as a bioink or its tissue engineering applications in injectable and 3D bioprinting forms.

BACKGROUND: The tissue engineering and regenerative medicine approach require biomaterials which are biocompatible, easily reproducible in less time, biodegradable and should be able to generate complex three-dimensional (3D) structures to mimic the native tissue structures. Click chemistry offers the much-needed multifunctional hydrogel materials which are interesting biomaterials for the tissue engineering and bioprinting inks applications owing to their excellent ability to form hydrogels with printability instantly and to retain the live cells in their 3D network without losing the mechanical integrity even under swollen state. METHODS: In this review, we present the recent developments of in situ hydrogel in the field of click chemistry reported for the tissue engineering and 3D bioinks applications, by mainly covering the diverse types of click chemistry methods such as Diels-Alder reaction, strain-promoted azide-alkyne cycloaddition reactions, thiol-ene reactions, oxime reactions and other interrelated reactions, excluding enzyme-based reactions. RESULTS: The click chemistry-based hydrogels are formed spontaneously on mixing of reactive compounds and can encapsulate live cells with high viability for a long time. The recent works reported by combining the advantages of click chemistry and 3D bioprinting technology have shown to produce 3D tissue constructs with high resolution using biocompatible hydrogels as bioinks and in situ injectable forms. CONCLUSION: Interestingly, the emergence of click chemistry reactions in bioink synthesis for 3D bioprinting have shown the massive potential of these reaction methods in creating 3D tissue constructs. However, the limitations and challenges involved in the click chemistry reactions should be analyzed and bettered to be applied to tissue engineering and 3D bioinks. The future scope of these materials is promising, including their applications in in situ 3D bioprinting for tissue or organ regeneration.