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Lee, et al.
           , and quadra-shaped EADs. This tendency can possibly   case.  Consequently,  the  average  values  of  H max  were
           be attributed to the difference in the internal area, where   measured to be 394, 220.6, 223.2, and 228.8 mm for the
           urine can flow during the reflex. When the internal areas   DJ stent without EAD and with single, double, and triple
           of each EAD were measured using the CAD model, the   penta-shaped EADs, respectively, as shown in Figure 7D.
           penta-,  quadra-,  octa-,  and  hexa-shaped  EADs  showed   The results showed that no significant variations existed
           areas of 46.53, 46.01, 45.94, and 44.94 mm , respectively.   in H max  between the single, double, and triple EADs. This
                                              2
           As the internal area increased, the EAD has the potential   might be because the pressure gradient, which helps the
           to be expanded because more urine flow can be trapped   EAD expand, was significantly decreased across the EAD
           inside the EAD when initial reflux occurs. In addition, the   at Position #1. Due to the decreased pressure gradient,
           external area (i.e., the spatial area between the expanded   the subsequent EADs (i.e., EADs at Positions #2 and #3)
           EAD wall and the inner wall of the ureter) will decrease   did not fully expand to sufficiently block the ureter line.
           as the internal area of EAD increases, thus increasing the   Thus, water flowed in the external area, and the EADs
           flow resistance in the ureter, which results in reduced H max .   at Positions #2 or #3 may not work. This also indicated
           Although  the  internal  area  of  the  quadra-shaped  EAD   that a single EAD attached at Position #1 (near the VUJ)
           is larger than that of the hexa- and octa-shaped EADs,   sufficed to mitigate urine reflux in the ureter line. From
           its anti-reflux efficiency is lower than that of the others.   the  results  shown  in  Figures  6 and 7,  a  single  penta-
           Here, the quadra-shaped EAD was flipped (overturned)   shaped EAD at Position #1 had the best performance in
           during  the  reflux  because  the  number  of  ribs  was  not   preventing  reflux,  and  the  anti-reflux  performance  did
           enough  to  maintain  the  overall  shape  against  reflex   not  change  significantly  depending  on  the  number  of
           pressure. Therefore, the quadra-shaped EAD showed the   attached EADs. In summary, the device with the highest
           worst anti-reflux efficiency in this study.         effectiveness and least irritation to patients was found to
               To further characterize the anti-reflux effectiveness   be a single penta-shaped EAD at Position #1 in this study.
           with  respect  to  the  number  of  attached  EADs,  an   Table 1 shows a comparison of anti-reflex devices
           experiment was performed using an increasing number   between  this  study  and  previous  literature  to  reduce
           of  penta-shaped  EADs,  which  exhibited  the  best   the  VUR.  It  was  noteworthy  that  previous  studies
           performance in the previous experiments. Figures 7A-C   have  focused  on  intraluminal  reflux  issues  whereas
           show the number of attached EADs (single, double, and   this  study  developed  the  anti-reflux  device  to  prevent
           triple)  at  the  various  positions. The  joining  part  of  the   the  extraluminal  reflux.  In  addition,  because  the
           EAD was located close to the side hole of the DJ stent to   material  used  in  this  study  (i.e.,  Ecoflex)  is  inherently
           avoid covering the side hole, and then the position was   biocompatible [44,45] , additional processes such as parylene
           determined. Due to the unequal distance between the side   C coating were not required on the anti-reflex devices to
           holes,  the  distance  between  the  positions  also  differed   enhance  the  biocompatibility.  To  characterize  the  anti-
           slightly. The distances between Positions #1 and #2 and   reflux performance, flow rate under the driven pressure
           Positions #2 and #3 were 17.5 and 22 mm, respectively,   was  measured  through  the  intraluminal  anti-reflux
           as  shown  in  Figures  7B and C.  Four  experimental   devices.  However,  because  urine  can  reach  the  renal
           conditions  (without  EAD  and  with  single,  double,  and   pelvis for a long time and the pressure was continuously
           triple penta-shaped EADs) were tested 5 times for each   supplied  during  experiments [21,23] ,  these  methods  could
                        A                                       D
                                                                D




                         B




                        C







           Figure 7. DJ stent assembled with (A) single penta-shaped extraluminal anti-reflux diode (EAD) at Position #1, (B) double penta-shaped
           EADs at Positions #1 and #2, and (C) triple penta-shaped EADs at Positions #1, #2, and #3. (D) Average values of maximum height in the
           urine reflux with respect to the number of EADs.

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