Development of silicone coronary bifurcation models for in vitro flow evaluation.
Atherosclerosis and hypertension are the most common causes of cardiovascular disease. Atherosclerosis is the thickening of a vessel wall due to absorption of fatty materials such as cholesterol and triglyceride. This absorption is due to compromised endothelial cell function lining the interior wall of a vessel and allows plaque to accumulate (2). Other than prescription medications, treatments for atherosclerosis include different strategies such as the use of catheters with drug coated balloons and stents. Bifurcations throughout the vascular system are among the most common locations that atherosclerosis may form (2). Within the span of an arterial bifurcation, uniform flow is disrupted and more complex mechanical situations exist (1). Analysis of a flow path complicated by a change in direction is much more complex than studying flow patterns through a single channel. Any situation regarding design optimization and procedure involving a stent implant for a bifurcation also requires greater understanding of the mechanics involved with these complications. For these purposes and possibly many more applications, modeling an arterial bifurcation may allow for widespread analysis of the system. Therefore, the purpose of this study is to develop a rapid and inexpensive method for developing consistent bifurcation models.
Sylgard 184 (provided by Dow Corning), a clear silicone based material, has been selected as an ideal compound for creating these models. The material has uniform elastic properties, it cures clear, and it can handle the higher temperatures used in the molding processes described below. Also, the mixture ratio may be altered to allow for multiple trials involving alternative material compliancy. After the Sylgard is cured, it is crystal clear. This aspect will allow for visual study of the internal conditions once an arterial model is affixed inside a bioreactor and flow is introduced. The curing process occurs relatively quickly at moderate temperatures, these restraints have proven to be appropriate for the methods involved with our procedure.
Injection Molding Process
In order to model an arterial bifurcation with precise dimensions, a two-stage mold design has been developed and designed using Solidworks as shown in FIGURE 1. Production of this design may be machined. However, approaching more complex compound bifurcation molds may require stainless steel 3D printing. The initial mold, made of stainless steel, will be injected with a low temperature melting material to form the inner cast, which is then placed into the secondary mold. An optically clear silicone based material is then injected into the secondary mold to cover the inner cast. Once the sylgard cures, the coated inner cast must be removed from the secondary mold and then melted out of the silicone, leaving a bifurcation shaped phantom.
Silicone Bifurcation Tubing and Preparation
For our purposes, sylgard may be injected into a mold to create a vessel shaped cast. The challenges involved with this approach include a need for a two-stage process. This gives rise to the selection process regarding suitable material for shaping the inner walls of the sylgard model. After the second stage, a bifurcation model formed around this material must be separated. In order to remove the inner cast from the model, it has been determined that a suitable material for this process could be melted out of the Sylgard, leaving a bifurcation shaped tube behind. The thermal elastic properties of the sylgard must also be taken into consideration. Once formed into the shape of a bifurcation, this cast may be used for extensive bench testing.
In order to fit the scale of our procedures, 10 grams of sylgard was used. Initially using a 10:1 ratio, 9 grams of the base material was mixed with 1 gram of the curing agent included in the Sylgard 184 silicone elastomer kit. Each 10-gram batch is used to create a single model.
To experimentally establish suitable materials for shaping the interior walls of the arterial model, an electric DC motor operating at 2 Volts was used. Straight cylindrical rods were then molded to size, 125mm in length and 5mm diameter, from the various materials tested which served as horizontal rotating shafts. 10 grams of Sylgard was then applied to the surface of these rotating rods and cured for one hour at 100 to form a tube. Materials tested in this fashion include modeling wax, thermoplastic (HEA-500) provided by Education Innovations, and Cerrosafe alloy consisting of 42.5% Bismuth, 37.7% Lead, 11.3% Tin, and 8.5% Cadmium. Once the rods were coated with sylgard, trials were carried out to insure that the materials could be removed from the model.
Cerrosafe alloy was selected as a suitable material to serve as the inner cast used for shaping the inner walls of the arterial model, surface smoothness was then addressed. Five samples were created from three different cooling rates including: room temperature cooling, quenching with running tap water, and quenching in a 40-50 bath. These fifteen samples were then compared to establish the most reliable method. Once consistently smooth samples were created, trials were carried out to establish an adequate removal process. Glass tubing with an inner diameter of 5mm was used to create fifteen 125mm long cylindrical Cerrosafe rods. A syringe was attached and used to draw liquid Cerrosafe preheated at 225 , approximately 20% above Cerrosafe melting temperature, into the glass tube. Once sealed from the bottom, the arrangement was quenched in 40-50 water to achieve a smooth finished surface. Thirty minutes following solidification, the glass tubes were fragmented to remove the Cerrosafe rods. These rods were then rotated on a horizontal axis for sylgard application. Next, the Cerrosafe filled sylgard tubes were set in a 225 oven with a vertical orientation. Of the fifteen trials, five were left alone, five were pre treated by inserting a film of water between the contacting surfaces of the Sylgard and Cerrosafe, and the last five were pre-treated by injecting a film of glycerin. Once the bulk of the material was removed, the Sylgard tubes were flushed with boiling water to remove remaining particles.
The modeling wax results demonstrated that the removal process compromised the clarity of the resulting Sylgard tube. The foggy appearance left behind was unsatisfactory for our purposes. The thermoplastic presented an even more difficult removal process due to its high viscosity and flow resistance. Results demonstrated that the lowtemp melting metal possessed the best properties for our application as it does flow well in its liquid phase. This Cerrosafe alloy has been chosen to serve as the inner cast for the two-stage design.
The Cerrosafe sample results, shown in FIGURE 2, infer that the most suitable method was quenching the alloy in a 50 bath. After attempting multiple techniques for removing Cerrosafe from Sylgard models, it proved most efficient to inject a film of glycerin between the contacting surfaces of these materials before using heat to melt the Cerrosafe for removal. The chance of the oil film being broken at the operating temperature of 212[degrees] F is insignificant. This method resulted in transparent Sylgard arterial models.
Based on results, it is apparent that Cerrosafe alloy may be used for the inner cast of the proposed twostage mold design. After initial injection, this material may be quenched in a 40-50[degrees]F water bath to achieve a smooth finished surface. Once this inner cast is coated with sylgard, glycerine may be injected to aid in removing Cerrosafe from within the Sylgard construct.
The significance of developing models for arterial bifurcations relate to the fact that disease mostly occurs near arterial bifurcations. Flow separation at bifurcations lead to low shear stress experienced by endothelial cells, leading to endothelial dysfunction and the progression of vascular disease.
Further stages of this study will involve manufacturing the two-stage mold design for testing. Upon completion of the bifurcations, non-invasive flow diagnostics will be used to measure and quantify temporal and spatial wall shear stress values of the models under physiological conditions.
This study has successfully identified Sylgard 184 and Cerrosafe alloy as compatible materials for a twostage injection molding strategy. The process will be used to model arterial bifurcations for the purpose of optically evaluating flow disturbances at bifurcation regions and their impact on vascular disease.
The authors acknowledge Mr. John Lyons and Mr. Terry Pritchett from The University of South Alabama: Engineering Machine Shop for their technical assistance.
[1.] Colombo A, Moses JW, Morice MC, Ludwig J, Holmes DR, Jr., et al. Randomized study to evaluate sirolimus-eluting stents implanted at coronary bifurcation lesions. Circulation 109: 1244-1249. 2004.
[2.] Alexander, R. Wayne, "Hypertension and the Pathogenesis of Atherosclerosis Oxidative Stress and the Mediation of Arterial Inflammatory Response: A New Perspective," Division of Cardiology, Emory University School of Medicine, Atlanta, GA.
Alex Parks, Saami K. Yazdani
Department of Mechanical Engineering University of South Alabama
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|Author:||Parks, Alex; Yazdani, Saami K.|
|Publication:||Journal of the Mississippi Academy of Sciences|
|Date:||Apr 1, 2014|
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