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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 SMP^4,5,6,7,8,9, 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 biodegradable^9,10. There are many uses for SMPs in the field of medicine^9,10, and stents^11,12 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 applications^2,3,13,14. 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.

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).

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 …

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 o…

Materials

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