Self-expanding stents are more flexible and restrained within a covering sheath, and by removing the sheath and uncovering the stent; the stent expands. The common materials used to make stents are stainless steel , platinum-iridium, Nitinol, cobalt-based alloys, titanium, and tantalum, along with some biodegradable, bio-resorbable materials such as magnesium and resorbable polymers. Because of anticipated growth in children, self-expandable stents are ideal to be used in children. There are several varieties of stent design that have been used in congenital field, including mesh, coilloop, ring and slotted tube, closed cell, open cell, and welded tube. Here some of the investigation that others did to create an optimum stent is reviewed. Such a stent is not yet available that combines all these requirements, however in this investigation it was tried to address some of these features in the designed stent. Sullivan et al., investigated the effect of the endovascular stent strut geometry on vascular injury, myointimal hyperplasia and restenosis. The authors used a Palmaz stent with rectangular struts and smooth corners and a novel stent with thicker struts and sharper corners to induce larger wall stress concentrations in a 90 days study. Sullivan et al., found that the thicker strut and sharper corners resulted in a statistically higher incidence rate of deep vascular injury compared to the Palmaz stent. As a result, square plant pot a higher restenosis rate observed with thicker and sharp corner struts.
At the end of their study the authors concluded that maintenance of an intact internal elastic lamina is crucial to prevent myointimal hyperplasia and restenosis in stented porcine iliac arteries. Sullivan et al., also found that superficial injury elicits a response that is independent of the stent strut geometry and vessel wall compression. Stent strut profile may, however, increase local vessel wall stress concentrations, leading to IEL rupture and an exaggerated response injury. Therefore, when stents are designed, extra attention should be given to the strut geometry. Bedoya et al., designed some generic stent models that represent the characteristics present commercially available stents. The authors deployed each stent in a homogeneous nonlinear hyperplastic artery model and evaluated them using commercially available finite element analysis software. Using computer simulation modeling Bedoya et al., suggested that stent designs incorporating a large axial strut spacing, blunt corners at bends, and higher amplitudes exposed smaller area of the artery to high stresses, while keeping enough radial force that is enough to keep the lumen open and restore flow. The mentioned articles were reviewed along with several others and they were used to characterize and design the self-expanding stent for this investigation. In this chapter, endovascular stenting and its effect on vascular arteries as well as how to design an optimum stent was reviewed.
A study summarizing the stent grafts that inhibited the growth of the arteries in rapid growing piglets was investigated. Also, clinical studies in children was reviewed and reported that a commercially available self-expanding stent grew with the artery; however, stents migrated in two cases and in other cases these stents caused significant stenosis and obstruction of the lumen in the patients. The effect of the chronic outward force on the lumen of the artery and how over stretching the arteries can cause neointima proliferation was reviewed. In addition, several papers discussing the requirements of a stent for pediatric application as well as how to design an optimum stent that can distribute the force and minimizes the damage to the arterial wall was reviewed. Utilizing all the findings we attempted to design a stent that can grow with small rapid growing arteries and induces the least response. Four potential pediatric self-expanding stent designs with varying numbers of struts, width, thickness, shape, length and architecture were created using Creo Parametric CAD as shown in Figure 1. The crimp profile of each design was simulated using SIMULIA Abaqus FEA software . Through crimp profile simulation, each design underwent iterations by adjusting the number of struts, width, and thickness in order to achieve the following pre-determined traits: crimp profile of < 6Fr, unconstraint diameter of 20mm, and length of 15 to 20mm with a radial force able to withstand vessel recoil after angioplasty. Radio-opacity for visualization under fluoroscopy was also a required but was not simulated.
A stent design with a single row, high amplitude, and low number of struts was selected that could be easily crimped to <6 Fr as indicated by an arrow in Figure 3.1. This design served as the basis for sub-selection of specific candidate stents. All histopathology analysis was performed at CVPath Institute Inc . Before processing for the histology, digital photograph was taken of the vessel and obtained Faxitron digital radiographs in the anterior-posterior and the lateral views. The radiographs demonstrated four nitinol bare metal stents, two measuring 15 mm long and two 20mm long and 10 to 18 mm in greatest diameter for 180 days study and two stents each 15mm length and 12 to 13mm in greatest diameter for 90 days study. An approximate 5 mm non-stented segment was present between the stents. The stents were submitted for embedding in Spurr resin and sectioning by the Exakt method. Proximal, mid, and distal non-stented aortic segments were submitted for paraffin embedding and routine histologic sectioning. To prepare the samples for plastic histology the stented aortic segments were dehydrated in a graded series of ethanol and infiltrated and embedded them in Spurr resin. After polymerization, transverse sections were sawed approximately 4 millimeters in thickness from the stents. Final slides were grounded from each of the plastic blocks to a final thickness of 19 to 90 microns using EXAKT Linear Grinding Technology. Each sample then polished and stained ground sections with hematoxylin and eosin . The mid-section of each stented segment was stained with Trichrome staining. All sections were examined by light microscopy for vessel wall integrity and inflammatory response. Proximal, mid, and distal non-stented aortic segments were submitted for paraffin embedding and routine histologic sectioning. After dehydration in a graded series of ethanol and infiltration with paraffin, the transverse sections for each segment were cut. Each block was sectioned at 4-6 microns and mounted them onto slides and stained with hematoxylin and eosin and Movat’s Pentachrome . All sections were examined by light microscopy for vessel wall integrity and inflammatory response. Representative fabricated self-expanding stents were tested in the radial force tester as explained in the method section and the hysteresis for each stent was generated . The angiographic images were analyzed, and the vessel diameter was measured for each stent prior to the implantation and after the duration of the study as explained in the method section. From the radial force study and the hysteresis results it was possible to find the amount of force exerted on the vessel at the time of implantation as reported in Table 4.1. The growth measurements and the stent chronic outward forces at the time of implantation was plotted in Figure 4.4. A strong correlation between the vessel growth and the stent force was not identified, rather a correlation between the location of the stent and growth and injury was observed. The low force stents in the distal side of the artery grew more than the high force stents in the proximal side. Stenting has emerged as a generally superior option as compared to balloon angioplasty and surgical repair for CoA in infants and children. Nevertheless, square pot the exponential growth of the arteries in children limits the use of stents and requires serial stent redialation and sometimes even fracture or surgical removal. Thus, among pediatric interventional cardiologists, there is a high level of interest in stents that can resorb or grow with the artery. Such stents could eliminate or reduce future reinterventions. This study represents the first effort to evaluate the effects of a purpose-built self-expanding stents on rapidly growing vessels. A range of novel self-expanding nitinol stents were specifically designed and manufactured and used to examine the effects of radial force and stents geometry on the biology of rapidly growing arteries.By varying the geometry and thickness of the nitinol in the stents, four stents with a variety of radial forces were designed, manufactured and tested. The outward force of each stent was measured at each diameter and used to correlate the effects of radial force on biology. These custom-made novel stents easily and reliably crimped and deployed in all the animals with good apposition to the aortic wall.
None of the stents limited arterial growth and there was continuing stent expansion with time, without erosion of the stents completely through the vessels. On average stented vessels grew 14% and 26% more in diameter at 90 and 180 days respectively than the distal and proximal non-stented segments of the vessels, suggesting that the force against the stented artery segments was higher than needed in all cases. The small vessels grew to larger degrees as compared to larger vessels . The experience with these stents suggests that even lower radial force stents may be ideal for this application. There was a favorable neointimal response and no aneurysm was noted in any of the stented vessels. Thus, angiographic results of each implantation universally showed that the stents were able to grow with and beyond the native arteries.Neointimal in growth after use of self-expanding stent has been reported to lead to the narrowing or stenosis of the arterial lumen, thus reducing the luminal area. Compression and tension by the stent struts, wall injury, and peri-strut inflammation due to responses to a foreign body object can cause in-stent stenosis as well as a disruption to the arterial wall leading to long term aneurysms and dissections. All the stents tested in this study formed a mature neointima layer around the stent struts and none had significant luminal stenoses . However, a wide range of damage to the IEL and media was observed: Figure 5.1A shows stent 4 in the iliac artery, with IEL and media laceration. Furthermore, Figure 5.1B shows Stent 4 in the abdominal aorta with compressed but intact IEL and media. All stented segments showed patency without any intraluminal thrombus or obstruction, with ˂20% stenosis in the worst case, despite compression and injuries of the IEL and the medial layer at 90 and 180 days. The long-term effects of the medial lacerations could not be assessed in a six month study. Fortunately, early re-endothelialization was ubiquitous: there was 100% endothelialization of all stents. The radial force of the stents could not be correlated with the stent’s effect on histopathology. No significant correlation was observed between the neointima formation and the forces in the designed stents. Overall injury, and inflammation, value for each stented section were scored according to Schwartz et al.’s scoring scheme . These criteria have been widely used in stent literatures. High injury scores, particularly scores of 2–3, have been reported to yield thicker neointima formation in the porcine coronary arteries. Because the force on each stented artery was a function of both the stent type as well as the diameter of the stented vessel, an attempt was made to correlate radial force with vascular injury and histopathology. While the outward force of the stents did not correlate to biological response, it was noted that smaller arteries in general had higher levels of injury and stenosis regardless of stent force. The mean average injury score was comparable among all stents with higher percent stenosis for stents on the distal side of the abdominal aorta. It is hoped that the data presented in this study will aid in the design of the ideal self expanding pediatric stent. Clearly, this observations in this limited study support the idea that such a device has the potential to improve outcomes in pediatric stenting. Nonetheless, many parameters need to be optimized in designing a pediatric self-expanding stent. This stent needs to have the ability to deploy via a 4-5 Fr system and then expand to 14-20 mm without overstretching the arterial lumen and causing stenosis, medial laceration or unwanted inflammatory responses. It needs to have enough force to at least growth with the vessel even after neointima formation. In this study, the stents in smaller vessels had higher mean nominal stent diameter to artery diameter ratios and higher degrees on medial injury. However, the long-term consequences of this medial injury remain unknown and it can be mitigated using lower radial force stents.