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      Fibrin-based Bioinks: New Tricks from an Old Dog

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          For the past 10 years, the main efforts of most bioprinting research teams have focused on creating new bioink formulations, rather than inventing new printing set-up concepts. New tissue-specific bioinks with good printability, shape fidelity, and biocompatibility are based on “old” (well-known) biomaterials, particularly fibrin. While the interest in fibrin-based bioinks is constantly growing, it is essential to provide a framework of material’s properties and trends. This review aims to describe the fibrin properties and application in three-dimensional bioprinting and provide a view on further development of fibrin-based bioinks.

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          Most cited references 100

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          Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part III: leucocyte activation: a new feature for platelet concentrates?

          Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this third article, we investigate the immune features of this biomaterial. During PRF processing, leucocytes could also secrete cytokines in reaction to the hemostatic and inflammatory phenomena artificially induced in the centrifuged tube. We therefore undertook to quantify 5 significant cell mediators within platelet poor plasma supernatant and PRF clot exudate serum: 3 proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), an antiinflammatory cytokine (IL-4), and a key growth promoter of angiogenesis (VEGF). Our data are correlated with that obtained in plasma (nonactivated blood) and in sera (activated blood). These initial analyses revealed that PRF could be an immune regulation node with inflammation retrocontrol abilities. This concept could explain the reduction of postoperative infections when PRF is used as surgical additive.
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            Molecular mechanisms of fibrinolysis.

            The molecular mechanisms that finely co-ordinate fibrin formation and fibrinolysis are now well defined. The structure and function of all major fibrinolytic proteins, which include serine proteases, their inhibitors, activators and receptors, have been characterized. Measurements of real time, dynamic molecular interactions during fibrinolysis of whole blood clots can now be carried out in vitro. The development of gene-targeted mice deficient in one or more fibrinolytic protein(s) has demonstrated expected and unexpected roles for these proteins in both intravascular and extravascular settings. In addition, genetic analysis of human deficiency syndromes has revealed specific mutations that result in human disorders that are reflective of either fibrinolytic deficiency or excess. Elucidation of the fine control of fibrinolysis under different physiological and pathological haemostatic states will undoubtedly lead to novel therapeutic interventions. Here, we review the fundamental features of intravascular plasmin generation, and consider the major clinical syndromes resulting from abnormalities in fibrinolysis.
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              Three-dimensional printing of Hela cells for cervical tumor model in vitro.

              Advances in three-dimensional (3D) printing have enabled the direct assembly of cells and extracellular matrix materials to form in vitro cellular models for 3D biology, the study of disease pathogenesis and new drug discovery. In this study, we report a method of 3D printing for Hela cells and gelatin/alginate/fibrinogen hydrogels to construct in vitro cervical tumor models. Cell proliferation, matrix metalloproteinase (MMP) protein expression and chemoresistance were measured in the printed 3D cervical tumor models and compared with conventional 2D planar culture models. Over 90% cell viability was observed using the defined printing process. Comparisons of 3D and 2D results revealed that Hela cells showed a higher proliferation rate in the printed 3D environment and tended to form cellular spheroids, but formed monolayer cell sheets in 2D culture. Hela cells in 3D printed models also showed higher MMP protein expression and higher chemoresistance than those in 2D culture. These new biological characteristics from the printed 3D tumor models in vitro as well as the novel 3D cell printing technology may help the evolution of 3D cancer study.

                Author and article information

                Int J Bioprint
                Int J Bioprint
                Whioce Publishing Pte. Ltd.
                International Journal of Bioprinting
                Whioce Publishing Pte. Ltd.
                29 April 2020
                : 6
                : 3
                [1 ]Department of Advanced Biomaterials, Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, Russia
                [2 ]Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia
                [3 ]Department of Molecular and Cell Pathophysiology, FSBSI Institute of General Pathology and Pathophysiology, Moscow, Russia
                [4 ]Department of Embryology, Lomonosov Moscow State University, Faculty of Biology, Moscow, Russia
                [5 ]Department of Traumatology, Orthopedics and Disaster Surgery, Sechenov First Moscow State Medical University, Moscow, Russia
                [6 ]Department of Urology, Sechenov First Moscow State Medical University, Moscow, Russia
                [7 ]Department of Polymers and Composites, NN Semenov Institute of Chemical Physics, Moscow, Russia
                [8 ]Department of Regenerative Medicine, Cell Science Research Centre, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
                [9 ]Institute of Photon Technologies, Federal Research Center Crystallography and Photonics RAS, Moscow, Russia
                Author notes
                [* ] Corresponding Author: Anastasia Shpichka, Department of Advanced Biomaterials, Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, Russia; ana-shpichka@
                Copyright: © 2020 Shpichka, et al.

                This is an open-access article distributed under the terms of the Attribution-NonCommercial 4.0 International 4.0 (CC BY-NC 4.0), which permits all non-commercial use, distribution, and reproduction in any medium provided the original work is properly cited.

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