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Investigation of process parameters of electrohydrodynamic jetting for 3D printed PCL fibrous scaffolds with complex geometries

            to be successful in engineering a tissue [1–2] , namely (i)   technology.  E-jetting has the same  working principle
            scaffold  should  biomimic  the  native  tissue  environ-  as  Electrospinning  technique  which is  widely
            ment  as close  as  possible,  (ii)  material  selection,   used to fabricate controlled porous scaffolds for tissue
            should  be  biocompatible  and  biodegradable,  (iii) ap-  engineering  applications [21–26] .  Various  studies  were
            propriate surface chemistry to promote cell attachment,   made  on the  effect of Electrospinning  parameters  on
            proliferation  and  differentiation,  (iv)  adequate  me-  the  electrospun  fibres [27–28] .  Subsequently,  the  most
            chanical  properties, and  (v)  fabrication  flexibility  to   important  parameters that have been  identified  were
            have  a  variety  of  shapes  and sizes.  The  utmost  cha-  namely, the volumetric charge density,  distance from
            llenge  with the current tissue engineering techniques   nozzle to collector, initial jet/orifice radius, relaxation
            is  imitation of  the  native  tissue  environment.  Tradi-  time,  and  viscosity [29] .  Numerous  novel  and  hybrid
            tional tissue engineering methods use 2D materials or   techniques of Electrospinning were  developed  in  or-
            scaffolds for cell culture and tissue construction. The   der to overcome the limitation of non-orientated ran-
            main drawback of 2D substrate is that it fails to pro-  dom  fibres from the  Electrospinning  process.  Bu  et
            vide the cell with its native architecture.  Most  impor-  al. [30]  developed a mechano-electrospinning technique
            tantly,  native  tissue  micro-architecture  is  highly   for fabricating oriented nanofibres and the controlled
            complex  and highly oriented due to  its  3D  environ-  parameter  was the  moving speed  of the substrate.
            ment. Obviously, when a 3D environment is provided   Chanthakulchan  et  al. [31]   developed  an  Electrospin-
            rather than 2D or 2.5D, the cells grow, proliferate and   ning-based  rapid  prototyping  method for fabrication
            differentiate  closer to the  native tissue [3–5] . There are   of patterned scaffolds but only achieved a certain level,
            several techniques to create a3D environment, such as   due to the challenges of controlling the vibration. Au-
                                                                        [32]
            solvent-casting particulate-leeching, gas foaming, ph-  yson et al.   studied the effect of various parameters
            ase separation, melt moulding, solution casting, freeze   of the hybrid Electrospinning / Fused Depositio Mod-
            drying and emulsion freeze drying, however, they suf-  elling (FDM) on the fabricated scaffold and concluded
            fer  from  the  drawback  of  producing  only  a foam   that  two  most  important  parameters  to  get  a  conti-
            structure, and not a  highly controlled porous 3D mi-  nuous jet are the voltage applied and the standoff dist-
            cro-architecture,  which  leads  to  several  other  prob-  ance between the nozzle and the substrate. On the other
                [6]
            lems .  Though  microscale  fabrication  technologies   hand, a low voltage near-field Electrospinning method
                                                                                   [33]
            like soft lithography were able to create a microscale   reported by Bisht et al.   was able to pattern nanofi-
            resolution scaffold [7–8] , they also suffer from several   bres  continuously on  both  2D  and  3D substrates, re-
            limitations  associated with inflexibility  in fabricating   spectively. Besides that,  other  vital  parameters  were
                                                                                                          [34]
            complex  geometries and the optimization of  scaffold   namely, the viscosity and elasticity of the polymer ink  .
                                                                 In this study, an E-jetting setup was built in-house
                      [9]
            architecture .  Electrospinning is looked  at as an al-  in order to fabricate 3D scaffolds out of PCL material.
            ternate technology  to  fabricate  nanofibrous  scaffolds   PCL material is widely used as a biomaterial for scaf-
            for tissue  engineering applications [10–14]   and  shows a   folds which possess extremely good mechanical pro-
            considerable  progress  with several reports portraying   perties. The structure of the printed scaffold depends
            its successfulness. Nonetheless, electrospinning tech-  on two important elements namely, the fibre diameter
            nology suffers  from the  limitation  of randomly ori-  and the pore size. The parameters of the E-jetting system,
            ented fibres and inability to fabricate a controlled   i.e. the supply voltage, solution concentration, nozzle-
            uniformly  porous scaffolds. 3D  printing  is currently   to-substrate distance, stage (printing) speed and solu-
            seen as the potential solution to fabricate layer by layer,   tion dispensing  feed  rate  greatly  influences  the fibre
            controlled  3D  porous  scaffolds [6,15–19] .  A  new term   diameter of the printed structure. Briefly, the relation
            known as  3D  bioprinting  has  emerged  recently  and   between these parameters and the fibre diameter were
            researchers  are  working  towards  the  realization  of   discussed in this work. Parameters were optimized and
            printing  functional  human  organs  with  this  novel   scaffolds  of  complex  geometries  i.e.  semi-lunar  and
            technology.  An  et  al. [20]   reviewed  vastly  on  various   spiral shapes have been successfully printed.
            state-of-the-art  3D  printing  technologies  for  tissue
            engineering  applications,  limitations  of  the  current   2. Experimental Section
            technologies  and  the  possible  future  improvements.
            Electrohydrodynamic Jetting, which is also known as   2.1 Materials
            EHD-Jetting  or E-jetting is  one  type  of  bioprinting   Acetate (Aladdin A116171, electronic grade, >99.7%)

            64                          International Journal of Bioprinting (2016)–Volume 2, Issue 1
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