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Kathleen Granger
Formation of biocompatible scaffolds from polymer blends
Introduction:
Synthetic scaffolds are essential for cultivating cells to be used in tissue regeneration,
which has tremendous value in the biomedical field. 1 This research is conducted to study
polymer blends and their phase separation to ultimately provide a three dimensional environment
for cells to grow in. Furthermore, since the area of polymer science is so expansive, there are
many unanswered questions that my research will address. The opportunity to explore this topic,
to seek and obtain a fundamental understanding of polymers, polymer blends, phase behaviors,
morphologies, and cell interactions with a polymer bicontinuous structure, will expand our
knowledge base and allow us to find new and/or more effective applications of polymers, which
will be useful for science fields across the board.
Personal Motivation:
My interest in synthetic scaffolds began following my experience in a very bad motor
vehicle accident in December 2012 in which my truck landed on top of me, breaking my neck
and rendering me paralyzed. I was rushed to Shreveport where I underwent immediate surgery.
After the procedure, I regained the use of my legs but I couldn’t walk correctly or use my hands.
I had to drop out of school and focus on my recovery. My days consisted of physical therapy,
bone stimulators, and a lot of medicine, but after a while I could walk and use my hands again. I
was dying to go back to school, so I moved back to New Orleans and enrolled in school again.
Before the accident I hadn’t declared my major, but I knew I liked math and chemistry, and after
what I went through during the recovery process, I became very interested in medicine and
biosynthetic materials. When my advisor and I were meeting, I told her about my interests. She
suggested chemical engineering, and I gave it a shot. During that first semester back in my
classes, I knew I was where I belonged. I loved what I was learning about and, as a chemical
engineering major at Tulane, I have a vast array of options to explore. Wanting more, this
semester I sought out an opportunity to conduct research working under one of my professors,
Dr. Albert. She presented me with some ideas that she had in mind for her lab that might fit my
interests. I have been conducting background research for the past few months and formulated
this project.
ResearchProject Overview:
In order to design a three-dimensional environment that is suitable for cells, I need to
select the right polymers such that their characteristics and interactions can be taken advantage of
to achieve my goal. First, the polymers should be incompatible with each other so that they are
able to phase separate. Then, upon adding a block copolymer compatibilizer with blocks that are
chemically identical to the two homopolymers, they will assemble together in such a way that
provides me with a bicontinuous structure (Figure 1).2 Second, I need one polymer (polymer A)
to exhibit robust structural properties such that it can stand on its. Third, I need the other polymer
(polymer B) to be easily removable from the structure, while the polymer A stays intact. Finally,
polymer A needs to be biocompatible so that it may serve its purpose of providing a favorable
environment to cells.
I decided to start with poly(dimethylsiloxane) (PDMS) for polymer A because it is
versatile and easy to work with. When cross-linked, PDMS acts like an elastic solid where the
polymer does not permanently deform under strain but rather returns to its original shape when
the strain is released.3 The elastic property changes so that the higher the concentration of cross-
Kathleen Granger
linking agent, the more solid the
polymer becomes, and with
insufficient cross-linking agent,
the polymer remains liquid.3
Since the cross-linking process
changes the state of PDMS, it is
commonly used in molds and as
a silicon substrate bonding
agent.3 Furthermore, PDMS is
considered chemically inert and
hydrophobic (water cannot
easily penetrate its surface),
which will allow it to remain
intact and be easily separated
from water-soluble polymers by
simply adding water.3
Poly(ethylene oxide) (PEO) on
the other hand, is hydrophilic and will dissolve in water, which will allow it to be easily removed
from the bicontinuous structure. 4 Thus, PEO was selected as polymer B. With these two
polymers, I will produce a channeled structure with openings that start and end on the surface.
The project work this summer will focus on obtaining the bicontinuous structure in
ternary blends of PDMS, PEO, and PDMS-b-PEO by manipulating the amounts of each polymer
relative to the other, amount of total polymer in solution, and, if need be, the amount of block
copolymer added to the polymer solution. I will also investigate the film under different
annealing times and temperatures, and find the best methods to cast a thick, evenly distributed
film. By examining the film at each condition, changing one variable at a time, I will be able to
map the behavior of my blend. This project will provide fundamental insight into blend phase
behavior, which can be used as a basis to model other blends. Once I explore the effect that each
parameter has on the polymer blend, I will have located the conditions for achieving the
bicontinuous structure needed for my project.
Future Aims and Directions:
Following the funding period, I will continue working on the project during the fall
semester with support from the Newcomb College Institute. With this grant, I will cross-link the
PDMS to strengthen the structure so that it will be stable enough to stand on its own when the
PEO is removed. I will then proceed to remove PEO by rinsing the film with water. In later
stages of the work, PDMS will be changed to poly(vinylmethylsiloxane) (PVMS), which will
add a vinyl group to the remaining structure, making it chemically reactive. The vinyl group
functionality will serve the purpose of allowing me to attach adhesive peptides to the surface of
the scaffold to interact with cells.1 Adhesive peptides containing the arginyl-glycyl-aspartic acid
(RGD) tripeptide will make PVMS a suitable place for cells to be able to migrate in.1
Conclusion
In closing, I am enthusiastic about how this research can fork off onto so many different
paths, leading to new discoveries. I am excited for the opportunity to work with my female
Kathleen Granger
mentor and learn from her, and to one day be able to engage other young female students in
science and research fields.
Schedule of Specific Aims:
Aim 1: (Month 1) Find the spin coating conditions that will produce a thick, evenly distributed
film.
a. Using homopolymer solutions (PDMS or PEO in toluene), I will vary the solution
concentration (1-10 wt% polymer in solvent) and
b. I will examine different means of spin coating to assess its effects of csting films.
This can be done by changing the spin speed (1000-5000 rpm) and by rearranging
the order of events when spin coating (dispensing the solution when the substrate
is stationary or spinning, i.e static versus dynamic). I will examine the film quality
using optical microscopy immediately after spin coating.
Aim 2: (Month 2) Identify blend compositions that will produce a bicontinuous structure.
a. I will start with 35% block copolymer mixed with 65% total homopolymer in a
ratio of PDMS to PEO of 50:50 as previous work reported in the literature has
indicated that bicontinuous structures are favored near this composition.2
b. Next, I will explore the phase separation behavior more fully by increasing the
PDMS:PEO ratio until I lose continuity (60:40, 70:30, 80:20, etc.). When I lose
continuity, I will then refine the composition increments to locate the phase
boundary more precisely (for example, I might look at 68:32, 66:34, 64:36,
62:38).
c. If this approach proves unsuccessful, I would next consider changing the amount
of block copolymer.
Aim 3: (Month 3) Determine the effect of annealing on bicontinuous structure. For the
compositions that produce a bicontinuous morphology after spin coating, I will see how
annealing affects the morphology by varying the annealing time and the annealing temperature.
1 Shoeb Ahmed, Jan Genzer, Ali E. Ozcam, Kirill Efimenko, and Michael C. Weiger. "Poly(vinylmethylsiloxane)
Elastomer Networks as Functional Materials for Cell Adhesion and Migration Studies." Biomacromolecules.2011,
12, 1265-1271.
2 Guoliang Liu, Mark P. Stoykovich, Shengxiang Ji, Karl O. Stuen, Gordon S. W. Craig, and Paul F. Nealey. "Phase
Behavior and Dimensional Scaling of Symmetric Block Copolymer-Homopolymer Ternary Blends in Thin Films."
Macromolecules, 2009,42, 3063-3072.
3 Brigham Young University, Department of Chemical Engineering. <http://www.photonics.byu.edu/PDMS.phtml>
Accessed February 2014.
4 Sigma-Aldrich Co. LLC. <http://www.sigmaaldrich.com/materials-science/material-science-
products.html?TablePage=20204110> Accessed March 2014.

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Granger.Deans.Research.Grant.Proposal

  • 1. Kathleen Granger Formation of biocompatible scaffolds from polymer blends Introduction: Synthetic scaffolds are essential for cultivating cells to be used in tissue regeneration, which has tremendous value in the biomedical field. 1 This research is conducted to study polymer blends and their phase separation to ultimately provide a three dimensional environment for cells to grow in. Furthermore, since the area of polymer science is so expansive, there are many unanswered questions that my research will address. The opportunity to explore this topic, to seek and obtain a fundamental understanding of polymers, polymer blends, phase behaviors, morphologies, and cell interactions with a polymer bicontinuous structure, will expand our knowledge base and allow us to find new and/or more effective applications of polymers, which will be useful for science fields across the board. Personal Motivation: My interest in synthetic scaffolds began following my experience in a very bad motor vehicle accident in December 2012 in which my truck landed on top of me, breaking my neck and rendering me paralyzed. I was rushed to Shreveport where I underwent immediate surgery. After the procedure, I regained the use of my legs but I couldn’t walk correctly or use my hands. I had to drop out of school and focus on my recovery. My days consisted of physical therapy, bone stimulators, and a lot of medicine, but after a while I could walk and use my hands again. I was dying to go back to school, so I moved back to New Orleans and enrolled in school again. Before the accident I hadn’t declared my major, but I knew I liked math and chemistry, and after what I went through during the recovery process, I became very interested in medicine and biosynthetic materials. When my advisor and I were meeting, I told her about my interests. She suggested chemical engineering, and I gave it a shot. During that first semester back in my classes, I knew I was where I belonged. I loved what I was learning about and, as a chemical engineering major at Tulane, I have a vast array of options to explore. Wanting more, this semester I sought out an opportunity to conduct research working under one of my professors, Dr. Albert. She presented me with some ideas that she had in mind for her lab that might fit my interests. I have been conducting background research for the past few months and formulated this project. ResearchProject Overview: In order to design a three-dimensional environment that is suitable for cells, I need to select the right polymers such that their characteristics and interactions can be taken advantage of to achieve my goal. First, the polymers should be incompatible with each other so that they are able to phase separate. Then, upon adding a block copolymer compatibilizer with blocks that are chemically identical to the two homopolymers, they will assemble together in such a way that provides me with a bicontinuous structure (Figure 1).2 Second, I need one polymer (polymer A) to exhibit robust structural properties such that it can stand on its. Third, I need the other polymer (polymer B) to be easily removable from the structure, while the polymer A stays intact. Finally, polymer A needs to be biocompatible so that it may serve its purpose of providing a favorable environment to cells. I decided to start with poly(dimethylsiloxane) (PDMS) for polymer A because it is versatile and easy to work with. When cross-linked, PDMS acts like an elastic solid where the polymer does not permanently deform under strain but rather returns to its original shape when the strain is released.3 The elastic property changes so that the higher the concentration of cross-
  • 2. Kathleen Granger linking agent, the more solid the polymer becomes, and with insufficient cross-linking agent, the polymer remains liquid.3 Since the cross-linking process changes the state of PDMS, it is commonly used in molds and as a silicon substrate bonding agent.3 Furthermore, PDMS is considered chemically inert and hydrophobic (water cannot easily penetrate its surface), which will allow it to remain intact and be easily separated from water-soluble polymers by simply adding water.3 Poly(ethylene oxide) (PEO) on the other hand, is hydrophilic and will dissolve in water, which will allow it to be easily removed from the bicontinuous structure. 4 Thus, PEO was selected as polymer B. With these two polymers, I will produce a channeled structure with openings that start and end on the surface. The project work this summer will focus on obtaining the bicontinuous structure in ternary blends of PDMS, PEO, and PDMS-b-PEO by manipulating the amounts of each polymer relative to the other, amount of total polymer in solution, and, if need be, the amount of block copolymer added to the polymer solution. I will also investigate the film under different annealing times and temperatures, and find the best methods to cast a thick, evenly distributed film. By examining the film at each condition, changing one variable at a time, I will be able to map the behavior of my blend. This project will provide fundamental insight into blend phase behavior, which can be used as a basis to model other blends. Once I explore the effect that each parameter has on the polymer blend, I will have located the conditions for achieving the bicontinuous structure needed for my project. Future Aims and Directions: Following the funding period, I will continue working on the project during the fall semester with support from the Newcomb College Institute. With this grant, I will cross-link the PDMS to strengthen the structure so that it will be stable enough to stand on its own when the PEO is removed. I will then proceed to remove PEO by rinsing the film with water. In later stages of the work, PDMS will be changed to poly(vinylmethylsiloxane) (PVMS), which will add a vinyl group to the remaining structure, making it chemically reactive. The vinyl group functionality will serve the purpose of allowing me to attach adhesive peptides to the surface of the scaffold to interact with cells.1 Adhesive peptides containing the arginyl-glycyl-aspartic acid (RGD) tripeptide will make PVMS a suitable place for cells to be able to migrate in.1 Conclusion In closing, I am enthusiastic about how this research can fork off onto so many different paths, leading to new discoveries. I am excited for the opportunity to work with my female
  • 3. Kathleen Granger mentor and learn from her, and to one day be able to engage other young female students in science and research fields. Schedule of Specific Aims: Aim 1: (Month 1) Find the spin coating conditions that will produce a thick, evenly distributed film. a. Using homopolymer solutions (PDMS or PEO in toluene), I will vary the solution concentration (1-10 wt% polymer in solvent) and b. I will examine different means of spin coating to assess its effects of csting films. This can be done by changing the spin speed (1000-5000 rpm) and by rearranging the order of events when spin coating (dispensing the solution when the substrate is stationary or spinning, i.e static versus dynamic). I will examine the film quality using optical microscopy immediately after spin coating. Aim 2: (Month 2) Identify blend compositions that will produce a bicontinuous structure. a. I will start with 35% block copolymer mixed with 65% total homopolymer in a ratio of PDMS to PEO of 50:50 as previous work reported in the literature has indicated that bicontinuous structures are favored near this composition.2 b. Next, I will explore the phase separation behavior more fully by increasing the PDMS:PEO ratio until I lose continuity (60:40, 70:30, 80:20, etc.). When I lose continuity, I will then refine the composition increments to locate the phase boundary more precisely (for example, I might look at 68:32, 66:34, 64:36, 62:38). c. If this approach proves unsuccessful, I would next consider changing the amount of block copolymer. Aim 3: (Month 3) Determine the effect of annealing on bicontinuous structure. For the compositions that produce a bicontinuous morphology after spin coating, I will see how annealing affects the morphology by varying the annealing time and the annealing temperature. 1 Shoeb Ahmed, Jan Genzer, Ali E. Ozcam, Kirill Efimenko, and Michael C. Weiger. "Poly(vinylmethylsiloxane) Elastomer Networks as Functional Materials for Cell Adhesion and Migration Studies." Biomacromolecules.2011, 12, 1265-1271. 2 Guoliang Liu, Mark P. Stoykovich, Shengxiang Ji, Karl O. Stuen, Gordon S. W. Craig, and Paul F. Nealey. "Phase Behavior and Dimensional Scaling of Symmetric Block Copolymer-Homopolymer Ternary Blends in Thin Films." Macromolecules, 2009,42, 3063-3072. 3 Brigham Young University, Department of Chemical Engineering. <http://www.photonics.byu.edu/PDMS.phtml> Accessed February 2014. 4 Sigma-Aldrich Co. LLC. <http://www.sigmaaldrich.com/materials-science/material-science- products.html?TablePage=20204110> Accessed March 2014.