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3D bioprinting technology for regenerative medicine applications

                                                   [3]
            instructions to  develop biological constructs . Bio-  puter-aided design techniques to make structures that
            printing can be defined as the use of materials science   closely  mimic  the  anatomical  structures of organs/
            and fabrication techniques to build  biological  con-  tissues. Based  on its  ability to produce organ  con-
            structs containing tissues, cells and biomolecules with   structs with native tissue biology, bioprinting has re-
                                                        [4]
            a  particular organization  and biological function .   ceived enormous attention in the field of regenerative
            Bioprinting techniques  have been recently explored   medicine. Even though bioprinting of a whole organ,
            for different biological applications due to their poten-  suitable for transplantation, is yet to be achieved, this
            tial to overcome most of the problems associated with   technology is  moving fast and  could soon satisfy
                                                [5]
            the  classical tissue engineering  methods . Classical   hopes to solve the shortage of organs for transplanta-
            tissue  engineering involves  the combination  of scaf-  tion in the future.
            folds, cells and compounds, such as growth factors [5,6] .   In this review article, we will first describe different
            Scaffolds  are seeded with the cells  and compounds   bioprinting methods such as extrusion-based printing,
            that promote tissue regeneration. Tissue engineering   cellular inkjet  printing, laser-assisted printing, inte-
            strategies have been utilized for the regeneration of   grated tissue organ printing  (ITOP)  and  robotic bio-
            various organs such as skin, trachea, bone, esophagus   printing used to develop scaffolds and other biomedical
                           [5]
            and myocardium . Though tissue engineering  ap-    constructs. Secondly, we describe the bioinks available
            proaches have  been  shown to be clinically  effective,   for bioprinting and the challenges involved in devel-
            all  scaffolds up-to-date  lack complex and intricate   oping a suitable bioink  that satisfies  the critical  re-
                                     [7]
            structures of the native tissue . In addition, the tissue   quirements for printing. Finally, the key applications of
            engineered scaffolds do not mimic the  native archi-  bioprinting in regenerative medicine are summarized,
            tecture of the tissues [8,9] .                     and its future directions are outlined.
               The key requirements of a tissue engineered scaf-
            fold are (1) biocompatibility; (2) biodegradability; (3)   2. Methods for Bioprinting Tissue/Organs
            adequate porosity; (4) mechanical strength; 5) biomi-  Bioprinting  of a tissue  or an  organ  is a complex
                                                 [6]
            metic structure and (6) therapeutic activity . Various   process which depends on the inherent  properties  of
            fabrication methods such as electrospinning, freeze-   the bioinks, printing techniques and  cellular  systems
            drying, phase separation,  gas foaming, particulate   used for printing. Furthermore, the resolution  of  the
            leaching and solvent casting have been developed to   printed structure is controlled by the parameters such
            produce tissue scaffolds [10] . However, tissue engineer-  as needle orifice size, surface tension and viscosity of
            ed scaffolds  do not completely  mimic the native ar-  the bioink, temperature, and humidity [14–16] . A typical
            chitecture  of the tissues, have  difficulties to support   bioprinting system can dispense bioinks onto a suita-
            the growth of cells in 3D and have problems to depo-  ble substrate of choice using a cartridge or a syringe.
            sit different cell types in the scaffolds at specified lo-  More advanced  bioprinting systems contain multiple
            cations [8,9,11,12] . Besides, many of  these fabrication   print heads, and each one can be loaded with the same
            methods involve the  use of organic solvents which   or different bioinks [17] . Printing patterns can be gener-
            impair  the cellular growth [13] . Further, tissue  engi-  ated, modified and  printed  using computer-aided
            neered scaffolds do not completely fulfill all the ideal   software such as CAD (Computer Aided Design). The
            requirements  needed for tissue  regeneration  as dis-  turnaround time taken for making modifications in the
            cussed above. On the other hand, bioprinting offers an   CAD files is just seconds to minutes making this
            alternative approach solving most of the problems   process easy  and user-friendly [18] . This is advanta-
            associated with the current tissue engineering methods.   geous to bioprint custom made structures such as tis-
            Tissue engineering strategies are  mainly involved in   sues and organs for transplantation. The prerequisites
            the development of scaffolds to promote regeneration/   to develop a bioprinting process comprise characteris-
            repair of tissue defects. While 3D bioprinting methods   tics, such as CAD, high resolution to obtain the  mi-
            can also be used to develop whole or parts of organs,   cro/nanoarchitecture and high-precision  to localize
            the main advantage is its potential to print whole or-  cells in a 3D environment. With these design strategies
            gans for transplantation purposes. Bioprinting can be   in mind, bioprinting is using biomimicry and 3D tis-
            used to fabricate  biological  constructs with defined   sue generation. The biomimicry approach enables the
            micro/nano architectures combining scaffolds with   fabrication of constructs with features that mimic the
            cells, and bioactive molecules. Bioprinting uses com-  native architecture of the tissue as close as possible [19] .

            10                          International Journal of Bioprinting (2016)–Volume 2, Issue 2
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