VENOUS GRAFTS AND NEOINTIMAL HYPERPLASIA TREATMENT
THE UTILIZATION OF KOHN-SHAM DENSITY FUNCTIONAL THEORY AND FREE RADICAL POLYMERIZATION FOR THE MITIGATION OF NEOINTIMAL HYPERPLASIA
ABSTRACT
August 2019 - June 2020
To improve patient outcomes from invasive pancreatic adenocarcinoma, an en bloc resection of the portal and mesenteric vein is suggested, but the subsequent 81% failure rate caused by graft stenosis and occlusion, limits the procedure’s applicability. To mitigate this complication, this project aimed to develop a new graft from a replacement polymer for PTFE and coat the graft with PNIPAm nanoparticles for steady drug release to limit the proliferation of vascular smooth muscles cells. Kohn Sham Density Functional Theory was used to compare the bulk modulus of two polymers, PTFE and PET, and free-radical polymerization with swelling tests were used to determine the optimal chemical concentrations for nanoparticle synthesis. It was determined that PET had a higher bulk modulus than PTFE by 16.6 GPa, possibly making it more viable as graft material, and 75% NIPAm, 25% Bis, and 42.5% PVA were the optimal concentrations of chemicals for nanoparticle synthesis with an average swelling ratio of 30.68%. From these results, a new graft was proposed made from PET and coated with PNIPAm nanoparticles with the predetermined concentrations.
BACKGROUND
Neointimal Hyperplasia is a common complication which arises post venous reconstruction where vascular smooth muscle cells (VSMCs) proliferate rapidly at the surgical site. The causes graft occlusion and stenosis ultimately leading to graft failure. Through this study, the researchers aimed to propose the development of a new venous graft made from a more sturdy and rigid material, coated with synthesized nanoparticles as a form of targeted drug delivery.
PHASE 1
In the first phase of the study, a computational mechanical analysis was performed on possible graft materials to replace the currently used PTFE. The material compared to PTFE was PET. Mechanical analysis was performed by utilizing Kohn-Sham Density Functional Theory to approximate the total chemical energy in a given volume of a system. A table of values was created and used to determine the bulk modulus of each chemical. A higher bulk modulus is indicative of a sturdier materials. PET had a higher bulk modulus than PTFE by 16.6 GPa and was deemed as possibly a more viable substitute for graft material.
PHASE 2
The second phase of the study focused on synthesizing nanoparticles with various concentrations of co-polymer, PVA. Multiple particles were synthesized and the possible correlation between an interpenetrating polymer network (IPN) with PVA and particle integrity/absorption was examined. It was determined that an IPN with PVA resulted in a more composite polymer with the highest swelling ratio. Finally, the optimal concentrations of chemicals for the synthesis of PNIPAm nanoparticles was determined
FUTURE STUDY
Future studies should focus on determining the maximum swelling ratio of the polymers, analyzing the collapsing properties of the polymer made from 75% NIPAm 25% Bis 42.5% PVA, and synthesizing nanoparticles and determining their respective absorption and collapsing properties. In addition, the possibility of a dependency between nanoparticle morphology and collapsing properties should be studied to determine the optimal nanoparticle shape for the longest drug release periods. Ultimately, the nanoparticles should be tested in cultures with muscle cells to quantify their effects on culture growth and size.
ANISH POTHIREDDY
Team Leader
Anish Pothireddy is a high school senior who attends the Governor's School at George Mason University. He is currently studying university physics with the intention of achieving a double-major in computer science and biology.
VISHNU LAKSHMANAN
Vishnu Lakshmanan is a high school senior who attends the Governor’s School at Innovation Park. He is currently enrolled in University Physics. He plans on graduating college with a computer science major coupled with an economics minor.
SAMYAK THAPA
Samyak Thapa is a high school senior who attends the Governor’s School at Innovation Park and Colgan High School. He is currently pursuing an advanced diploma with a focus on physics at the Governor’s School. He plans on majoring in computer engineering in college with a minor in finance
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