BEE 4530 - 2018 Student Papers

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Optimization of Hydrogel-based Cellular Encapsulation for Diabetes Treatment
Bao, Ed; Shariati, Kaavian; Alimena, Nicole; Mehrabyan, Tigran (2018-05-10)
Cell encapsulation is an efficient and cost-effective treatment for a variety of endocrine and hormonal disorders. The use of cells to deliver therapeutics is an especially desirable means drug delivery may be achieved, and serves to eliminate issues associated with other methods of drug delivery. The application of these methods to Type 1 Diabetes is a promising area of research, and may potentially be a functional cure. As the use of cell encapsulation devices vary, the need for parameter analysis and optimization for a diabetes-focused encapsulation devices becomes apparent. More importantly, the potential complications faced by effective cell encapsulation devices must be considered in design. The study attempted to observe the selectivity of transfer of chemical species pertinent to a pancreatic islet cell encapsulation device. The complications associated with the availability of such chemical species were also modeled with respect to variation in the parameters of the device. The Type 1 Diabetes model was designed with a cylindrical geometry, and three primary layers consisting of an islet cell containment core, a nanofiber(nylon) mesh layer, and an outer hydrogel layer. The impacts of glucose and oxygen availability on insulin secretion were of specific concern to the study. The hydrogel must be appropriately permeable to the flow of glucose, insulin, and oxygen. These concerns were addressed and studied through the use of COMSOL Multiphysics , a commercial analysis software. A two-dimensional axisymmetric model was implemented in order to observe the diffusivity-driven mass transfer of chemical species, and their associated reactions. The computational modeling approach was chosen in order to study the effect and impact of parameter variation on the efficacy of such a device, and to computationally optimize these parameters. A steady-state study was conducted on the model with concentrations of blood glucose and oxygen as boundary conditions, as well as an insulin concentration of zero at the outermost boundary assuming total insulin removal. Encapsulated islets under low oxygen conditions showed a loss of viable tissue, and the development of a necrotic core. Using a critical oxygen concentration of 0.001 mM in conjunction with implementing parameter variation against standard model conditions, the critical radiuses before cell death were calculated for several models. For the multiaxial transfer device, the critical radius before the presence of any cell death or necrosis was determined to be 0.00172 m after identifying the key modulator of cell life and insulin production to be oxygen. The same process was repeated with a model in which mass flux was zero at both ends of the device, resulting in a significantly lower critical radius of 0.00122m. Additionally, the computations revealed that insulin concentrations were not strongly modulated by glucose availability. The production of insulin is more heavily influenced, within the steady state conditions after a meal, by local oxygen concentrations. Iterations of the model were repeated with various hydrogels, nanofiber widths, and islet loads in order to identify gelatin as the most efficient hydrogel for insulin flux, and dispersed islets as being necessary for optimal insulin secretion. Validation of the model and results were conducted through comparison to experimental information, as well as through model C which validated the physical approximation of islets being homogeneously distributed within the core. As the efficacy of cell-based diabetes treatments is more seriously considered, the need becomes apparent for the development of computational model such as those implemented in this study, which reveal the impacts of parameters and designs chosen on device efficiencies . Such a model may be implemented in future research of alternate encapsulation methods for Type 1 Diabetes, as well as other disorders as they pertain to the endocrine and hormonal systems. Approaches to address these directional shifts may involve the consideration of additional parameters and domains.
Modeling Countercurrent Arteriovenous Heat Exchange and Blood Flow in a Finger Exposed to Cold
Albano, Greg; Slowskei, Lauren; Puckett, Lee; Reynolds, Aaron (2018-05-09)
It is widely accepted among the scientific community that countercurrent heat exchange between blood vessels developed as an advantageous evolutionary trait for preserving body heat in humans and other animals; however, much of the theory behind this is qualitative in nature4,5. In this study, we provide a quantitative model of countercurrent heat exchange in a human finger exposed to freezing temperatures. We seek to compare the impact of changes in various physiologically-based parameters on convective heat loss from the finger. By comparing the net effects of several parameters to that of countercurrent heat exchange, we can make a concrete claim about how important the presence of countercurrent exchange as an evolutionary trait is to the preservation of core body temperature. In this study, we consider the tissue temperature within a human finger that is losing heat to the surrounding cold blowing air, while also gaining heat from blood vessels that participate in countercurrent heat exchange. To investigate the mechanism of countercurrent heat exchange in a human finger, we used COMSOL, a multiphysics finite element analysis and simulation software, to develop a simple geometry and replicate the heat exchanging properties of the human finger when exposed to extreme cold or freezing external conditions. The two major blood vessels we consider will be separated and surrounded by finger tissue that has its own physical properties. Heat is transferred from the owing blood, through the finger tissue, and is lost to the surrounding cold environment. Using this model, we were able to analyze how the blood and tissue temperature gradients change with position and time over while exposed to external freezing conditions. The model demonstrated the advantages of countercurrent exchange as a critical trait in mediating convective heat loss in an organism, thereby supporting the accepted idea that it evolved as a mechanism to preserve heat. In transferring much of the heat from the arterial blood to the venous blood, instead of to the tissue, the body retains that thermal energy as opposed to allowing it to escape as convective heat loss. The net effect is a decrease in the average tissue temperature, which equates to a decrease in the flux of outward heat, henceforth maintaining core body temperature at the expense of that of the extremities. The results of this study provide insight on the relative importance of different physiological responses to the cold. While other physiological adaptations may serve to mitigate convective heat loss and therein preserve core body temperature, the most significant factor affecting heat loss was the distance between vessels. Thus, consistent with qualitative assessments, the evolution of blood vessel geometries has proven mathematically to play a critical role in the conservation of body heat. By understanding the mechanistic underpinnings of how this works, we can form a better basis of understanding for future bio-inspired designs.
Shear Stess-Induced Nanoparticle Drug Delivery in the Right Coronary Artery
Allan-Rahill, Nash; Iruvanti, Sushruta; Miller, Nick; Sarubbe, Jerry (2018-05-10)
Shear stress-sensitive nanoparticles are a promising new field for drug delivery. This novel method may allow the targeted release of drugs such as statins or vasodilators to areas of high shear in the bloodstream, as occurs near a stenosis. Previous work claims that shear stress-sensitive nanoparticles may deliver a targeted release of clot-busting or cholesterol-fighting drugs to arterial plaque [1]. However, these studies have only examined flow characteristics near plaques and have not considered the movement of nanoparticles within these flows or the complex process of drug diffusion from the particle's shear location into the plaque. The study outlined here considers the entire process from nanoparticle entry upstream of the plaque through drug diffusion into the tissue. A right coronary artery with a Type I plaque morphology was designed using the 3D CAD design software SolidWorks®. COMSOL Multiphysics®, a commercially available modeling software, was used to model blood flow past this plaque with a varying inlet velocity to simulate pulsatile flow. Particle diffusion through the blood and subsequent drug diffusion into the tissue were simulated. Average dimensional values and flow velocities for men were used since they are more at risk for developing atherosclerosis. The results of these simulations showed that the plaque buildup at 35% stenosis causes sufficient shear stress to break the nanoparticles, releasing the drug into the blood. Most drug, once it was released from the nanoparticles, was found to diffuse into the downstream half of the plaque. Moreover, it was found that the optimal breaking shear stress of the nanoparticles for targeted drug delivery to the stenosis was nearly the maximum shear stress achieved in the flow at 75 Pa, while the optimal infusion concentration is close to the maximum clinically allowable at 0.045 mol/m3 [2]. This computational study has filled an important void in the body of research on this novel drug delivery method. It has verified the rupture of nanoparticles under 35% stenotic conditions while showing subsequent drug diffusion patterns, which suggests that this method may not be suited for targeting drug delivery to arterial plaques. Further research should examine the effects of arterial wall compliance, consider non-Newtonian blood flow, and test realistic plaque geometries obtained, for example, via intravascular ultrasound (IVUS). Though shear stress-sensitive nanoparticle drug delivery may not ideally target drug to arterial stenoses, this novel method may prove useful for modeling tumorigenic systems, where fluid shear stress has been shown to affect cancer cell motility.
Computational Study of Hydrogel Ring Device for Ocular Drug Delivery
Hanif, Sarah; Lim, Abigail; Sit, Hilarie; Tan, Wan Qing Melissa (2018-05-10)
Researchers have developed many different kinds of ocular drug delivery devices. However, most address anterior eye disorders—very few are designed specifically for the treatment of posterior eye diseases. A recently-developed hydrogel ring device is capable of delivering therapeutic quantities of the drug Ofloxacin to treat ocular infections at the back of the eye—a region typically difficult to access via systemic (e.g. ingestion of pills) and topical (e.g. eye drops) methods. Despite promising preliminary in vivo test results, much remains unknown about the precise drug transport pathway from the hydrogel ring to the posterior segment of the eye, as well as how design parameters may be altered to increase drug delivery efficiency. The aim of this work is to fully characterize the drug release and transport characteristics from the hydrogel, to ocular tissues (anterior and posterior), as well as provide a quantitative method for the optimization of various hydrogel ring design parameters. To achieve the abovementioned goals, we built a computational model using COMSOL Multiphysics to simulate the release of Ofloxacin from the hydrogel ring and to obtain the resulting drug distribution in ocular tissues at various time points. Using the model, we monitored the transient Ofloxacin concentration profile over the entire eye, for a treatment period of ten hours. Our results showed that while Ofloxacin diffuses to the anterior region much more quickly than to posterior tissues, Ofloxacin concentrations do successfully accumulate to therapeutic levels in the posterior tissues during the simulated ten-hour treatment period. This finding supports the therapeutic potential of the hydrogel ring for the treatment of posterior eye diseases. We also performed optimization analyses to determine the ideal set of hydrogel ring design parameters for the treatment of infections caused by three bacterial species commonly associated with ocular disorders: Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. Preliminary findings suggest that the combination of an initial mass of 3 mg/m3 of Ofloxacin in the hydrogel and an Ofloxacin diffusivity of 3.11X10−9 m2/s in the hydrogel provide the best possible therapeutic outcome (from the range of values tested) for the treatment of E. coli and S. aureus infections. To our best knowledge, there is no existing computational model that simulates drug transport through the entire human eye from an ocular drug delivery device. We believe that our computational model will be highly useful for quantitative device characterization of the hydrogel ring, as well as in the optimization of the hydrogel ring design for the treatment of posterior eye disorders. This work may also serve as a model and reference for future computational work on ocular pharmacokinetics and/or ocular drug delivery devices.
Investigation of Pulp Pressure Dynamics by Modeling the Topical Application of 50% Lidocaine HCl in the Human Premolar
LaViolette, Aaron K.; Furness, Samuel P.; Rodriguez, Alexander; Alamgir, Ashab S. (2018-05-10)
The purpose of this research is to perform a time study on local anesthetics in dental surgery to provide insight on the inner workings pulp pressure dynamics. The dynamics of the pulp pressure when the dentin surface is exposed to atmospheric conditions are currently not understood. Verifying the ability of a high drug concentration to overpower the tooth’s pressure gradient will provide evidence of a unique phenomenon in which diffusion overcomes fluid flow and uncover the physics of drug transport in the tooth. Quantifying this physics is the goal of this paper. The time for a tooth to lose and regain sensitivity was measured with finite element modeling in COMSOL Multiphysics ® version 5.3. This model was built based on a clinical study which shows that the high concentration of lidocaine used (50% w/v or 500 mg/mL) was strong enough to overcome the natural pressure gradient from the pulp to the outside air. The clinical study reported that patients lost tooth sensitivity between 20 and 30 minutes and regained tooth sensitivity between 50 and 60 minutes. Within the tooth, there are three distinct layers: enamel, dentin, and pulp. Inside of the pulp, there are blood vessels which cause degradation of the lidocaine and nerve endings which lose sensation upon binding to lidocaine. In the clinical study, a 3 mm diameter hole was drilled 3 mm deep through the enamel exposing the dentin layer (modeled at the center to retain axisymmetric geometry). The model used the mass transport and Darcy’s Law equations to model the physical situation. Drug application was modeled with 10 minutes of drug exposure in the hole followed by hydrated gauze. Pressure was modeled with an exponential pressure decay with varying time constants. The time constant was optimized to find which physical pressure situation produced results closest to the results of the clinical study. This was accomplished using an objective function which assigned penalties to each time constant based on whether the tooth was numb and sensitive at the appropriate times found during the clinical study. This gave a value for a time constant. Sensitivity analysis was run on parameters approximated from the literature. After sensitivity analysis, sensitive parameters were varied and new optimizations were run to produce a range of values for the time constant. This report found that tooth pulp pressure can be modeled with first order decay upon dentin exposure to atmospheric conditions. The decay was found to be governed by a time constant of 7 minutes and 5 seconds. After sensitivity analysis and variation of sensitive parameters, the time constant was found to fall in a range of 5 minutes and 15 seconds to 9 minutes and 25 seconds. The pressure dynamics were found to be particularly sensitive to hydraulic conductivity of pulpal fluid in dentin, and diffusivity of lidocaine in dentin. This paper offers a glimpse into the poorly understood pressure dynamics in a tooth during dental surgery. It is reported that bulk fluid movement from pressure in human dentin produces solvent drag or the effect of slowing inward diffusive flux of exogenous solutes. The quantitative description of these pressure effects is important for future medical applications and understanding this evolutionary phenomenon. Future research directions include first finding exactly accurate parameters by experimentation to fine tune the model. Also, using a 3D geometry with different drilled hole placements could produce a more accurate description of the process.
Computational Modelling of Water Transport in Hydrocolloid Wound Dressing, DuoDERMⓇ CGF, and Design Recommendations
Cabot, Jackson; Klein, Robert; Sasso, Grainger; Sasso, Grainger; Zhang, Viola (2018-05-10)
Hydrocolloids, and further hydrogels, have arisen as attractive next-generation wound dressings because of their modularity and ability to retain moisture. Hydrocolloids, like DuoDERM Ⓡ CGF, are intended for partial and full thickness wounds. They may be used for minor burns, cuts, tears, abrasions, as well as lacerations, ulcers, and some traumatic or surgical wounds. A computational simulation of water transport in wounds with hydrocolloid dressings was implemented in order to understand the mechanisms of hydrocolloid wound dressings as they relate to water transport. The ideal dressing will maintain the wounded tissue at physiological water content levels while also retaining moisture within the dressing itself to promote re-epithelialization of tissue. This study aims to determine the effectiveness of current wound dressings with respect to retaining moisture and maintaining the skin at physiological levels of water content. This study further seeks to optimize current wound dressing design parameters in order to improve water retention above the wound bed and maintenance of physiological skin water content. To study the transfer of liquid water in skin and an example hydrocolloid wound dressing, a computational model was built in COMSOL Multiphysics Ⓡ Modeling Software using a multifrontal direct solver (MUMPS). This model primarily detailed water transport processes in the skin (stratum corneum, epidermis, and dermis) with an example hydrocolloid dressing DuoDERM Ⓡ CGF (hydrocolloid and polymeric barrier layer). The use of the model can be extended to larger or smaller wound areas as well as different types of hydrocolloid dressings. The parameters of the materials can be easily altered to fit new materials being simulated, however the model is only valid up to the time right before the hydrocolloid would start to degrade. The model considered the skin layers, wound surface, hydrocolloid, and polymeric barrier layer to be a 2D, axisymmetric cylinder. Water (mass) transport was considered diffusion in porous media in the skin and diffusion in the hydrocolloid and polymeric layers. The swelling effect, typical of hydrocolloids, was modeled using deforming geometry. After validating the model, an objective function was created in order to quantify the performance of the model based on its ability to maintain physiological water content in the skin as well as its ability to retain moisture in the hydrocolloid domain above the wound bed. Using this objective function, the material properties of the hydrocolloid dressing were altered in order to obtain an optimal solution, where the dressing would maintain an ideally moist environment. The results confirmed that the hydrocolloid wound dressing retains moisture but does not satisfactorily maintain wounded tissue near physiological levels of water content. The optimization suggested the variation of two hydrocolloid parameters, the diffusivity and the partitioning coefficient between the skin and hydrocolloid, in order to improve its performance. Lowering the diffusivity of the hydrocolloid resulted in a higher water concentration above the wound bed. Decreasing the partition coefficient (an effect observed by increasing the hydrophobicity of the hydrocolloid) reduced the flux of water from the wound to the dressing. The combined effect of a reduced diffusivity and partition coefficient allowed greater regions of the wound to retain physiological water content levels and improved water retention near the wound bed. These results will inform the design of future generations of wound dressings and elucidate difficulties in the use of hydrophilic wound dressings like hydrocolloids and hydrogels.
Life Under the Ice: The Effect of Ice Development on Photosynthetic Submerged Plants
Bishop, Sochima; Callahan, Rowan; Sendelbach, Luke (2018-05-10)
Many submerged plants rely on photosynthesis as a means to obtain sugars and oxygen. Plants that inhabit deeper regions have limited exposure to sunlight, as light irradiance decreases exponentially with increasing distance from the surface. During the winter, ice growth over a lake adds additional light obstruction. Ice sheets may grow to a thickness that reduces light availability to a level that no longer supports photosynthesis. While modeling the growth of ice sheets computationally is not new, there have not been studies linking ice sheet growth with the obstruction of light used for photosynthesis. This study investigates the conditions necessary to grow an ice sheet sufficiently thick to reduce the light irradiance 20 meter below the surface to 10% of the irradiance hitting the surface of the ice. Our investigation looks at upstate New York and considers a region containing the expanding ice sheet, the water below it, and an insulating 2 centimeter thick layer of snow that only exists when an ice sheet does. To model the growth of the ice sheet we modelled the heat transfer and treated the ice layer as a solid with a no flow liquid water domain underneath. We included Syracuse specific time-dependent air temperature conditions, a convective heat transfer coefficient, radiative flux from sunlight and radiation from the atmosphere at the surface of the lake to mimic common wintertime conditions. We also used zenith angle information from upstate New York latitude and longitudes. A semi-infinite boundary at a constant temperature was established at the bottom of the domain to simulate a deep lake. Additionally, we incorporated water’s temperature dependent density in modeling heat transfer in the domain. Finally, we implemented these design specifications (dimensions, equations, boundary conditions, and physics) in COMSOL software for numeric analysis for the duration of an entire month. After implementing the model with the above conditions, we were able to show that our model successfully computes the growth and decay of ice over time for small northern lakes. We obtained a model of the temperature variation within the ice layer and water underneath at discrete points in time, as well as the depth of the ice sheet over the course of the time period. Our model demonstrated that ice formation never reached a thickness sufficient to impede photosynthesis in our Syracuse location given normal conditions and moderate future weather shifts. However, our model includes flexibility to incorporate a range of different weather conditions, which may be used to monitor whether climate change can drive ice formation enough to inhibit photosynthesis.
Cool-sculpting: Optimizing Total Fat Loss During Cryolipolysis
Rosario, Nicole; Kemp, Jazmin; Mushtaq, Yasmeen; Boter, Michelle (2018-05-19)
Cryolipolysis has become a more prevalent, non-invasive fat loss procedure. Multiple studies have been performed to assess the effi ciency of cryolipolysis techniques. This research includes optimization of cooling temperature used in the procedure and finding how the geometry of suction cup leads to better fat loss. Analysis of how adipose cells cool and at what rate they undergo apoptosis would allow us to optimize the total fat loss during the procedure. Current cryolipolysis research has not compared applicator shapes and their dimensions. This study investigates how altering the dimensions of the applicator head can increase fat loss and possibly be beneficial to more patients. The region of fat being exposed to the treatment was approximated as a 3D slab that includes a skin layer and subcutaneous adipose tissue layer. The rate of heat flux to surrounding adipose tissue was observed under various head geometries in order to maximize fat cell loss. Geometries were designed in order to maximize the surface area to volume ratio, while keeping the volume of fat in the applicator head constant. As a result, locations of cold application were maximized, with the aim of achieving a greater percentage of damaged fat cell loss. To perform a sensitivity analysis, the dimensions of the cooling applicator and therefore the 3D slab were changed, temperature was decreased, and metabolic heat were changed. Heat transfer and the mass degradation were simulated using the commercial analysis software COMSOL multiphysics. The amount of fat loss during cryolipolysis reaches a threshold. The original applicator model showed around a 5-6% total volume of cooled fat cells after one 60 minute session. Patients usually have to have multiple cooling sessions in order to reach a 20-50% total fat reduction over the course of a few months; therefore a 5-6% total volume of fat cells cooled supports this. Consequently the procedure is not suitable for patients who want to lose more than 10 pounds of fat; even after undergoing multiple treatments because a small amount of fat cells are cooling to the optimal temperature and dying. After designing a new applicator head with an increased surface area to volume ratio, we were able to increase the volume of cooled fat. This analysis can give rise to new technology that can be used in other cosmetic surgery procedures. Currently, this cryolipolysis procedure is only available to patients who are within 5-10 pounds of their weight goals. By changing the dimensions of the applicator head and by changing the amount of fat loss that occurs post-op, the new shape of the applicator head can expand accessibility of the treatment to patients who are not within 5-10 pounds of their weight goal.

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