Summary
Using a 3D printer, a shape memory polymer filament is extruded to form a branched tubular structure. The structure is patterned and shaped such that it can contract into a compact form once folded and then return to its formed shape when heated.
Abstract
Branched vessels, typically in the form of the letter "Y," can be narrowed or blocked, resulting in serious health problems. Bifurcated stents, which are hollow in the interior and exteriorly shaped to the branched vessels, surgically inserted inside the branched vessels, act as a supporting structure so that bodily fluids can freely travel through the interior of the stents without being obstructed by the narrowed or blocked vessels. For a bifurcated stent to be deployed at the target site, it needs to be injected inside the vessel and travel within the vessel to reach the target site. The diameter of the vessel is much smaller than the bounding sphere of the bifurcated stent; thus, a technique is required so that the bifurcated stent remains small enough to travel through the vessel and expands at the targeted branched vessel. These two conflicting conditions, that is, small enough to pass through and large enough to structurally support narrowed passages, are extremely difficult to satisfy simultaneously. We use two techniques to fulfill the above requirements. First, on the material side, a shape memory polymer (SMP) is used to self-initiate shape changes from small to large, that is, being small when inserted and becoming large at the target site. Second, on the design side, a kirigami pattern is used to fold the branching tubes into a single tube with a smaller diameter. The presented techniques can be used to engineer structures that can be compacted during transportation and return to their functionally adept shape when activated. Although our work is targeted on medical stents, biocompatibility issues need to be solved before actual clinical use.
Introduction
Stents are used to widen narrowed or stenosed passages in humans, such as blood vessels and airways. Stents are tubular structures that resemble the passages and mechanically support the passages from further collapsing. Typically, self-expanding metal stents (SEMS) are widely adopted. These stents are made from alloys composed of cobalt-chromium (stainless-steel) and nickel-titanium (nitinol)1,2. The downside of metal stents is that pressure necrosis can exist where the metal wires of the stent come into contact with the live tissues and the stents are impacted. Furthermore, the vessels of the body can be irregularly shaped and are much more complex than simple tubular structures. In particular, there are many specialized clinical procedures to install stents in branched lumens. In a Y-shaped lumen, two cylindrical stents are simultaneously inserted and joined at a branch3. For each additional branch, an additional surgical procedure needs to be conducted. The procedure requires specially trained doctors, and the insertion is extremely challenging due to the protruding features of the branched stents.
The complexity of the shape of bifurcated stents makes it a very suitable target for 3D printing. Conventional stents are mass produced in standardized sizes and shapes. Using the 3D printing fabrication methodology, it is possible to customize the shape of the stent for each patient. Because shapes are made by repeatedly adding layer-by-layer of the sectional shapes of the target object, in theory, this method can be used to fabricate parts of any shape and size. Conventional stents are mostly cylindrical in shape. However, human vessels have branches, and the diameters change along the tubes. Using the proposed approach, all these variations in shapes and sizes can be accommodated. Additionally, although not demonstrated, the used materials can also change within a single stent. For example, we can use stiffer materials where support is needed and softer materials where more flexibility is required.
The shape changing requirement of bifurcated stents calls for 4D printing, namely, 3D printing with the additional consideration of time. 3D printed structures formed using specialized materials can be programmed to change their shape by an external stimulation, such as heat. The transformation is self-sustained and requires no external power sources. One special material that is suitable for 4D printing is an SMP4,5,6,7,8,9, which exhibits shape memory effects when exposed to a material-specific triggering glass transition temperature. At this temperature, the segments become soft so that the structure returns to its original shape. After the structure is 3D printed, it is heated to a temperature slightly above the glass transition temperature. At this point, the structure becomes soft, and we are able to deform the shape by applying forces. While maintaining the applied forces, the structure is cooled down, becomes hardened and retains its deformed shape, even after the applied forces are removed. Subsequently, at the final stage, when the structure needs to return to its original shape, such as the moment when the structure reaches the target site, heat is supplied so that the structure reaches its glass transition temperature. Finally, the structure returns to its memorized original shape. Figure 1 illustrates the various stages previously explained. The SMPs can be easily stretched, and there are some SMPs that are biocompatible and biodegradable9,10. There are many uses for SMPs in the field of medicine9,10, and stents11,12 are one of them.
The patterns of the stents and the folding design follow the Japanese paper cutting design called "kirigami." This process resembles the well-known paper folding technique called "origami," but the difference is that in addition to folding, cutting of the paper is also allowed in the design. This technique has been used in arts and has also been applied in engineering applications2,3,13,14. In short, kirigami can be used to transform a planar structure to a three-dimensional structure by applying forces at specifically designed spots. In our design requirements, the stent needs to be a simple cylindrical shape when inserted into the pathways, and the cylinder should divide along its length where each half should unfold to a fully cylindrical shape at the targeted branched vessel. The solution lies in the fact that the main vessel and the side branches are folded into a single cylinder such that the side branches will not interfere with the walls of the vessels during the insertion. The unfolding command signal comes from the increase in the ambient temperature above the glass transition temperature of the SMP. Additionally, the folding will be conducted outside the patient body by softening the 3D printed bifurcated stent and folding the side branch into the main vessel.
Conventional methods required the insertion of multiple cylindrical stents whose number equals the number of branches. This method was inevitable because the protrusions of the side branches hampered the walls of the pathways and made it impossible to insert a complete bifurcated stent in its entirety. Using the kirigami structure and 4D printing, the above problems can be resolved. This protocol also shows the visualization of the effectiveness of the proposed method using a silicone vessel model fabricated after the shape of blood vessels. Through this mock-up, the effectiveness of the proposed invention during the insertion process and further possibilities of new applications can be seen.
The purpose of this protocol is to clearly outline the steps involved in printing an SMP using a fused deposition modeling (FDM) printer. Additionally, techniques involved in deforming the printed bifurcated stents to the folded state, the insertion of the folded bifurcated stents to the target site, and the signaling and unfolding of the structure to its original shape are given in detail. The demonstration of the insertion utilizes a silicone mock-up of blood vessels. The protocol also provides the procedures involved in fabricating this mock-up using a 3D printer and molding.
Subscription Required. Please recommend JoVE to your librarian.
Protocol
1. Blood vessel mock-up design for the demonstration
- Set the diameter of the proximal main vessel to 25 mm, the diameters of the distal main vessel and the side branch equal to 22 mm. Set the total length of the vessels equal to 140 mm. Set the length of the proximal main vessel, the distal main vessel and the side branch to 65 mm, 75 mm and 65 mm, respectively. The complete blood vessel is shown in Figure 2 and Figure 3.
- Print the computer model of the branched vessel by using an FDM 3D printer. Use a polycarbonate filament.
2. Blood vessel mock-up fabrication by molding
- Create a box-shaped container that will house the 3D printed part. Set the container dimensions to 110 x 105 x 70 mm and use an acrylic plate.
- With the 3D printed branched vessel placed at the center of the box, gently pour the silicone inside the container to minimize bubble formation. Dry the liquid silicone and harden it for 36~48 h.
- Remove solidified silicone from the container and cut it in half to remove the 3D printed part. Rejoin the divided silicone at the cut plane. The resulting joined body is the blood vessel mockup. The final result is shown Figure 4.
3. Design of the branched stent based on kirigami
NOTE: The size of the branched stent is made to snuggly fit inside the Y-shaped pathway of the blood vessel mockup. The interior is made hollow, and the surface tubular meshes are designed to functionally fold and return to the full unfolded configuration.
- Design the trunk of the bifurcated stent following wavy patterns similar to conventional stents. Set the diameter of the trunk to 22 mm and the length of the trunk to 38 mm.
- Design the bifurcated branches to be a cylinder, as shown in Figure 5B. Set the diameter of the branch to 18 mm and the length of the branch to 34 mm.
- Set the total length of the stent to 72 mm. The final shape is shown in Figure 6.
4. 3D printing with SMP filaments
- Print the bifurcated stent in an FDM 3D printer using an SMP filament. The major composition of this filament is polyurethane. The commercial vendor also provides these filaments in the form of pellets so that the end user can also add additional substances to tailor the characteristics of the material (Figure 7).
- Use slicing software for model slicing and to control the settings of the 3D printer. Set the extruder temperature to 230 °C and the temperature of the printer bed to room temperature. Set the layer height to 0.1 mm to minimize the staircase effect.
- Set the printing speed to 3,600 mm/min. Set the amount of interior fill percentage to 80%. Include the supporter formation during printing, which is needed because the structure is hollow in the interior. Figure 8 illustrates the printing process.
5. Smoothing out the surface
NOTE: The following steps are required because rough surfaces can damage the vessels by abrasion.
- Remove the supporters using cutters (Figure 9A). The supporters are attached at the interior of the stent. When removing the stents, exercise extreme caution to avoid tearing the stents.
- Rub the surface against sandpaper (Figure 9B) to remove the layer lines, striations, or blemishes on the printed surface. Repeated polishing may be needed where the supporters are removed by the cutters.
- Paint the surface using a spray in a well-ventilated location, and wear a personal mask. Clean, sand, and dry the surface. Protect from overspraying by applying thin layers of repeated paints. Use black paints to enhance the contrast between the silicone vessel mockup and the stent (Figure 9C).
6. Deforming the bifurcated stent
- Place the bifurcated stents in warm water such that the temperature is above the glass transition temperature. When the stent becomes softened, push one half of the branch against the other half. Nest one half within the other half, as shown in Figure 10A.
- Fold the two branches into a single cylinder so that it can travel through the main vessel. Perform the same nesting process to the other branch. Subsequently, the two halves of the cylinders are closed into one, as shown in Figure 10B.
7. Insertion of the bifurcated stent into the vessels
- Fill a tank with warm water. Set the water temperature to 55-60 °C. Immerse the silicone vessel mockup inside the tank. Orient the mockup such that the main vessel is above and the branches are below.
- Insert the folded bifurcated stent into the opening of the silicone vessel mockup from above. Orient the folded bifurcated stent such that its branches are towards the opening. The folded bifurcated stent will start to expand, and the lower branches will divide such that each branch will slide towards its mating pathway from the bifurcation core of the Y-shaped vessels (Figure 12).
Subscription Required. Please recommend JoVE to your librarian.
Representative Results
In this protocol, we showed the procedures required to fabricate a bifurcated stent. The stent uses a kirigami structure to allow the bifurcated stent to fold into a compact cylindrical tube, which is very suitable for sliding through the narrow pathways of blood vessels. The SMP allows the folded structure to return to its original shape when the temperature reaches the glass transition temperature. The original shape, 3D printed using the SMP material, closely matches the branched vessels. In other words, the interior surface of the branched vessels, where the bodily fluid is flowing, is offset further inside by the prescribed thickness of the fabricated stent. A solid form is created between the interior surface and the offset surface. This solid form exactly fits the vessel and can be used as a model for the stent. Due to the ability of the SMP to return to its memorized shape, the folded structure will return to the predeformed shape once heated above its glass transition temperature. The two branched stents can be easily formed into half-cylindrical tubes by taking advantage of the kirigami structure. The two halves of the cylinders are merged into one cylinder, and the united structure has been shown to slide through the main vessel and reach the bifurcation area. To return the folded structure to its original shape, the experiment was performed in a water at a temperature of 60 °C. It has been shown that each side branch will divide, and each branch will go to its pairing vessels in the bifurcation area. The bifurcated stent was inserted into the Y-shaped vessels as a whole requiring only a single operation. This is much simpler than the conventional operation requiring insertions of each branching stent separately. These results show that it is possible to simplify the stent insertion operation to a single operation, whereas previous stent operations required the number of insertions of side branch stents to be the same as the number of side branching blood vessels.
Figure 1: Shape transformation diagram of the SMP. (A) The printed shape is the original shape. (B) When heated above the glass transition temperature (Tg), the structure becomes soft. When a force is applied, the structure is deformed to the desired shape. (C) The structure is fixed to a deformed shape by cooling. (D) When heated again above the glass transition temperature, a recovery force that returns the deformed shape to its original shape is generated. (E) The recovered shape is the same as the original shape. Please click here to view a larger version of this figure.
Figure 2: The names of the parts of a Y-shaped blood vessel are shown. Y-shaped vessels have a main vessel and a side branch. The main vessel consists of a proximal main vessel and a distal main vessel. The proximal main vessel is divided into the side vessel and the distal main vessel, which lies above the bifurcated core. Please click here to view a larger version of this figure.
Figure 3: Design of the blood vessel. (A) Right side view of the modeled blood vessel. This side is designed as a hook shape to express the three-dimensional nature of a real blood vessel in the human body. (B) Front view of the modeled blood vessel. Rotated view of the Y-shaped blood vessel according to Figure 2. Please click here to view a larger version of this figure.
Figure 4: Silicone blood vessel mock-up. A container made with acrylic plates and 3D printed blood vessel models are used as a mold to create this mock-up. The mock-up was made using liquid silicone, which was hardened after drying. The front view (A) and the side view (B) are shown. Please click here to view a larger version of this figure.
Figure 5: Design of the bifurcated stent’s branches using kirigami. (A) Conceptual design of the stent branch. The sheet is cut along the black line. Subsequently, external forces are applied at the specific points in the specified direction, as marked by the red arrows. The resulting geometry of the operations described in A is shown to the right, B. A planar sheet has been transformed into a three-dimensional tubular shape. (B) The design of a tubular stent based on the kirigami structure. Please click here to view a larger version of this figure.
Figure 6: The three-dimensional model of the bifurcated stent. The trunk uses wavy patterns quite similar to the conventional stent design. The two upper branches utilize kirigami structures. Please click here to view a larger version of this figure.
Figure 7: SMP filament. It is produced in a filament form that is easy to print using a commercial 3D printer. Please click here to view a larger version of this figure.
Figure 8: Picture of a 3D printed bifurcated stent using an FDM (fused deposition modeling) 3D printer. The 3D printed bifurcated stent is attached to the 3D printer bed using a double-sided gluing tape to prevent the output from slipping. Please click here to view a larger version of this figure.
Figure 9: Postprocessing of the 3D printed result. (A) Removal of the supporters. The bifurcated stent is hollow in the interior and thus requires a supporter during 3D printing. The removal of the supporters is required. (B) The bifurcated stent with the supporters removed. (C) The bifurcated stent is spray-painted to clearly contrast it from the silicone pathways. Please click here to view a larger version of this figure.
Figure 10: Illustration of the deformation and the recovery shape of the bifurcated stent. (A) The stent is heated to make it malleable. Subsequently, forces are applied to fold the branches into a half-cylindrical shape. (B) Half-cylindrical shapes are combined into a single tubular structure. The folding procedural steps are from the left to the right, and the recovery process is the reverse of the folding, which occurs from the right to the left. Please click here to view a larger version of this figure.
Figure 11: The original and deformed state of the bifurcated stent. Notice the deformed shape is the shape of a cylinder and can be easily inserted into the trunk portion of the blood vessels. When the compactly folded shape is heated above the glass transition temperature, the shape returns to its original bifurcated shape. Please click here to view a larger version of this figure.
Figure 12: The time lapsed shots of the recovering procedures of the folded stent inserted into the branched blood vessels are shown. (A) The procedural unfolding steps when the bifurcated stent is inserted into the Y-shaped vessels are shown. Initially, a single cylindrical tube is inserted. The inserted tube starts to divide once reaching the bifurcated core and returns to its unfolded original shape. (B) The timed images of the experiment. The upper left shows the insertion of the folded tube into the opening trunk of the vessel. The upper right shows the division of the inserted stent at the bifurcated core. The bottom row shows the recovery of the stent and the exact fit of the final bifurcated stent that perfectly fits the morphology of the targeting blood vessels. Please click here to view a larger version of this figure.
Please click here to download this file.
Please click here to download this file.
Supplementary Files. Digital model of the vessel model.
Subscription Required. Please recommend JoVE to your librarian.
Discussion
Stents are often used to clear the clogged internal pathways such as the blood vessels and airways of patients. Surgical operation of inserting stents requires the careful consideration of the patient’s illness and human anatomical characteristics. The shape of the vessel is complex, and diverse branching conditions exist. However, the standard stent operational procedures are based on mass-produced stents with standard sizes. In this protocol, we showed how to personally tailor the fabrication of the stent based on the exact geometry of the blood vessels. In doing so, we designed the stent so that the interior is made hollow and the surface tubular meshes will fold and return to the full unfolded configuration when activated. We have targeted bifurcated stents, which are typically used during operations with multiple numbers of tubular stents. The design of our bifurcated stents is performed as a whole, and a single operation is required regardless of how complex and how many branches exist in the branched vessels. The key enabling technique that we have used to solve the problem is the SMP. The ability of the structure to return to its original shape is anticipated, so forces are exerted to prevent the expanded pathways from the re-contraction.
Another important idea is the use of a kirigami structure. The most difficult part is how one can shrink the Y-shaped branches into a compact cylindrical tube. This problem has been solved using a kirigami structure. Each branch is folded into half cylinders and then merged together.
We found an optimal temperature of 220-230 °C to memorize the bifurcated stent shape. Based on this fact, the extruder temperature was set to 230 °C. When the temperature was set above this temperature, the accuracy of the shape was compromised. When the temperature is set below this temperature, the SMP clogged the 3D printer nozzle. If different materials are used, then the extruder temperature should be adjusted. The temperature of the printer bed was set at room temperature. We experienced unwanted deformation of the structure when the printer bed temperature was set higher. Additionally, it is recommended that the interior fill is set to above 70%. It is recommended to avoid or minimize the generation of supporters, as they will impose additional postprocessing burdens.
The glass transition temperature of the SMP used was 55 °C, and the softening of the printed structure occurred above this temperature. When folding the printed bifurcated stent, we immersed the whole structure into a water heated bath above this temperature. When different SMPs are used, one should first find the glass temperature of the particular material. The recovery characteristics of other temperatures can be found in Kim and Lee15, where faster responses were shown for higher temperatures.
We used an FDM 3D printer to fabricate the bifurcated stent. The size of the produced stent was too large to be inserted into real human vessels. Researchers should consider using different types of 3D printers or 3D printers with smaller nozzle diameters. The latter is technically difficult because SMPs are often very viscous and will easily clog the nozzle, especially when smaller diameter-sized nozzles are used.
The limitations of our work are as follows. The glass transition temperature was too high to be used inside patients. Furthermore, this particular material was not proven to be biocompatible. It is also preferable that the stent be biodegradable when the vessel no longer needs the stent to support it from collapsing. These problems could be solved with the use of other types of SMPs and further extensive live experiments.
Subscription Required. Please recommend JoVE to your librarian.
Disclosures
The authors have nothing to disclose.
Acknowledgments
This work was supported by the Institute of Information & Communications Technology Planning and Evaluation (IITP) grant funded by the Korean government (MSIT) (No. 2018-0-01290, the Development of an open dataset and cognitive processing technology for the recognition of features derived from unstructured humans (police officers, traffic safety officers, pedestrians, etc.) motions used in self-driving cars) and the GIST Research Institute (GRI) grant funded by the GIST in 2019.
Materials
| Name | Company | Catalog Number | Comments |
| Fortus380mc | Stratasys | Fortus 380mc | FDM 3D printer for printing blood vessel mock-up |
| Moment1 3D printer | Moment | Moment 1 | FDM 3D printer for printing bifurcated stent |
| PC(white) Filament Canister | Stratasys | PC(white) Filament Canister | PC filament for printing blood vessel mock-up |
| PLM software NX 10.0 | Siemens | NX 10.0 | 3D CAD modeling software |
| Sandpaper | DAESUNG | CC-600CW | Smooting out the surface of the bifurcated stent |
| Shape Memory Polymer filament | SMP Technologies Inc | MM-5520 | Shape memory polymer filament |
| silicon | Shinetus | KE-1606 | silicon for blood vessel mock-up |
| Simplify3D | Simplify3D | Simplify3D 4.0.1 | Slicing software for model slicing |
References
- Migliavacca, F., et al. Stainless and shape memory alloy coronary stents: a computational study on the interaction with the vascular wall. Biomechanics and Modeling in Mechanobiology. 2 (4), 205-217 (2004).
- Kuribayashi, K., et al. Self-deployable origami stent grafts as a biomedical application of Ni-rich TiNi shape memory alloy foil. Material Science and Engineering A. 419, 131-137 (2006).
- Suwaidi, A. I., et al. Immediate and long-term outcome of intracoronary stent implantation for true bifurcation lesions. Journal of the American College of Cardiology. 35 (4), 929-936 (2000).
- Mao, Y., et al. Sequential self-folding structures by 3D printed digital shape memory polymers. Scientific Reports. 5, 13616 (2015).
- Ge, Q., Qi, H. J., Dunn, M. L. Active materials by four-dimension printing. Applied Physics Letters. 103, 131901 (2013).
- Wu, J., et al. Multi-shape active composites by 3D printing of digital shape memory polymers. Scientific Reports. 6, 24224 (2016).
- Chen, S., Zhang, Q., Feng, J. 3D printing of tunable shape memory polymer blends. Journal of Materials Chemistry C. 5, 8361-8365 (2017).
- Qi, G., et al. Multimaterial 4D printing with tailorable shape memory polymers. Scientific Reports. 6, 31110 (2016).
- Lendlein, A., et al. Biodegradable, elastic shape-memory polymers for potential biomedical applications. Science. 296, 1673-1676 (2002).
- Lendlein, A., et al. Shape memory polymers. Angewandte chemie. 41, 2034-2057 (2002).
- Baer, G. M., et al. Fabrication and in vitro deployment of a laser-activated shape memory polymer vascular stent. BioMedical Engineering OnLine. 6, 43 (2007).
- Wache, H. M., Tartakowska, D. J., Hentrich, A., Wagner, M. H. Development of a polymer stent with shape memory effect as a drug delivery system. Journal of Materials Science: Materials in Medicine. 14 (2), 109-112 (2003).
- Shyu, T. C., et al. A kirigami approach to engineering elasticity in nanocomposites through patterned defects. Nature Materials. 14, 785-789 (2015).
- Rossiter, J., Sareh, S. Kirigami design and fabrication for biomimetic robotics. Proc. SPIE. 9055, Bioinspiration, Biomimetics, and Bioreplication. 90550G (2014).
- Kim, T., Lee, Y. G. Shape transformable bifurcated stents. Scientific Reports. 8, 13911 (2018).
