Primary Advisor: – Dr. Barbara Knutson- College of Engineering - Chemical & Materials Engineering
Co-Advisor: Dr. Stephen Rankin – College of Engineering - Chemical & Materials Engineering
Lab Mentor: Mahsa Moradipour – College of Engineering - Chemical & Materials Engineering
Plants have a broad range of defenses to ensure their survival, including the production of antimicrobial compounds to protect them from microorganisms. Plant-based antimicrobials have the potential to serve as supplements (in livestock production, for instance) and as functional precursors for antifouling and antimicrobial coatings. A common mechanism of antimicrobial action is their interaction with the lipid bilayer in the cell membranes of microorganisms, altering the transport of ions and small molecules across the cell membrane. This project will focus on the synthesis of surfaces (nanoparticles and thin films) with covalently-bound plant-derived antimicrobial compounds, focusing on derivatives recently developed from monomers and dimers of lignin. The interaction of functionalized nanoparticles with synthetic lipid bilayer will be investigated using a quartz crystal microbalance (QCM). Lipid bilayers will first be assembled on the QCM sensors and then the QCM will be used to detect uptake of particles by the layer and subsequent bilayer disruption. The effect of particle functionalization and concentration on bilayer uptake and disruption will be investigated and compared to the corresponding effect of the antimicrobial in solution. These uptake studies will be coupled with investigations of ion binding and antimicrobial activity for the design of structures which insert into lipid bilayers and effect membrane transport. Success of this research will result in strategies to design antimicrobial surfaces using the same principles as nature.
Primary Advisor: Dr. Brad Berron – College of Engineering – Chemical and Material Engineering
Lab Mentor: Cong Li– College of Engineering – Chemical and Material Engineering
Heart disease is the number one cause of death worldwide. For end-stage heart failure, the only solution would be heart transplantation, however there is extremely limited the number of donors available for transplantation, and the recipients require long-term immune suppressants to prevent organ rejection. Our lab is trying to develop bioartificial organs suitable for transplantation. Building a heart requires a scaffold that can support cardiac function. Decellularized scaffolds made from alpha-galactose deficient hearts are stripped of all immunogenic materials. One of the critical challenges of converting decellularized scaffolds into viable therapeutic option is the reseeding of cells. The positioning and density of cells within the matrix are potentially the greatest challenges to recellularize hearts. The beating heart is composed of dozens of specialized cell types that need to be accurately positioned for proper function. Recellularizing by vascular perfusion or intramyocardial injection only offers approximate control over position but lacks cell precision, orientation, and density We seek to pattern the cells in the position they are needed, to create artificial hearts with better function. We will first focus on cell patterning on a glass slides. The slide will be patterned with a cell-binding chemical with UV light. Our goal is to develop patterning conditions that support cells sticking only in targeted parts of the slide. From there, we will work with a team in cardiology to apply the patterning method to heart tissues.
Primary Advisor: Dr. Martha Grady – College of Engineering – Mechanical Engineering
Co-Advisor: Dr. Brad Berron – College of Engineering – Chemical & Materials Engineering
Lab Mentor: Dr. Martha Grady – College of Engineering – Mechanical Engineering
Cell therapies have been developed to assist in the repair of damaged tissues [1-4]. For example, stem cells have been injected into the heart after damage due to myocardial infarction or heart failure [1-2]. One critical challenge is that the vast majority of cells injected into the heart tissue disappear within a week . One way to improve cell retention is by increasing adhesion to target sites with a cell coating, but a novel method is needed to quantify any advances in adhesion due to coatings. REU students will work on the development of the laser spallation technique [6-8] to apply and quantify stresses at critical cell-substrate interfaces. The student will explore adhesion of Jurkat cells to a multi-layer system terminating in a layer of streptavidin designed to mimic an idealized biological surface. The student will learn to navigate an optical setup, pulsed and continuous wave lasers, as well as a high-rate oscilloscope. In addition, characterization of the loaded and unloaded regions will require the aid of fluorescence staining and microscopy, SEM, and image analysis software such as Image.
[1.] Diaz-Herraez, P.; Saludas, L.; Pascual-Gil, S.; Simon-Yarza, T.; Abizanda, G.; Prosper, F.; Garbayo, E.; Blanco-Prieto, M. J., Transplantation of adipose-derived stem cells combined with neuregulin-microparticles promotes efficient cardiac repair in a rat myocardial infarction model. J Control Release 2017, 249, 23-31.
[2.] Sanganalmath, S. K.; Bolli, R., Cell therapy for heart failure: a comprehensive overview of experimental and clinical studies, current challenges, and future directions. Circ Res 2013, 113 (6), 810-34.
[3.] Freyman, T.; Polin, G.; Osman, H.; Crary, J.; Lu, M.; Cheng, L.; Palasis, M.; Wilensky, R. L., A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J 2006, 27 (9), 1114-22.
[4.] Houtgraaf, J. H.; den Dekker, W. K.; van Dalen, B. M.; Springeling, T.; de Jong, R.; van Geuns, R. J.; Geleijnse, M. L.; Fernandez-Aviles, F.; Zijlsta, F.; Serruys, P. W.; Duckers, H. J., First experience in humans using adipose tissue-derived regenerative cells in the treatment of patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2012, 59 (5), 539-40.
[5.] Hong, K. U.; Li, Q. H.; Guo, Y.; Patton, N. S.; Moktar, A.; Bhatnagar, A.; Bolli, R., A highly sensitive and accurate method to quantify absolute numbers of c-kit+ cardiac stem cells following transplantation in mice. Basic Res Cardiol 2013, 108 (3), 346.
[6.] Hagerman, E.; Shim, J.; Gupta, V.; Wu, B., Evaluation of laser spallation as a technique for measurement of cell adhesion strength. J Biomed Mater Res A 2007, 82A (4), 852-860.
[7.] Shim, J.; Hagerman, E.; Wu, B.; Gupta, V., Measurement of the tensile strength of cell-biomaterial interface using the laser spallation technique. Acta Biomater 2008, 4 (6), 1657-1668.
[8.] Hu, L. L.; Zhang, X.; Miller, P.; Ozkan, M.; Ozkan, C.; Wang, J. L., Cell adhesion measurement by laser-induced stress waves. J. Appl. Phys. 2006, 100 (8).
Primary Advisor: Dr. Guigen Zhang – College of Engineering - Biomedical Engineering
Co-Advisor: Dr. Yu Zhao – College of Engineering – Biomedical Engineering
Lab Mentor: Dr. Yu Zhao – College of Engineering – Biomedical Engineering
This summer research experience will provide the student(s) basic exposure to biomedical engineering research in one to two areas (if time permits): 1) basic science exploration by taking advantage of thermodynamics-driven computational modeling, and 2) hands-on development.
- On the modeling side, we will investigate drug release behavior of periodontal treatment drugs.
Understanding drug release kinetics and the underlying transport/reaction mechanisms is crucial for the design of efficient microfluidic devices. Combination of different types of drugs as well as carriers leads to different representative drug release profiles. In this part of the learning experience, the student(s) will learn how to develop computational models which incorporate multiple possible release mechanisms by starting from previously developed models on diffusion of drugs encapsulated in porous carrier. This part of learning will entail
- Collect review/original papers on modeling of drug release process and identify existing gaps between mathematical/physical models and real behavior of drug release.
- Learn how to use COMSOL, especially modules relevant to transport and chemical engineering. Get familiar with how to set up COMSOL model to study problems of interest.
- Expand the capability of existing models, try to gain new knowledge and obtain new insight into the drug release process by incorporating as many relevant physics as possible.
- On the hands-on development side, we will take advantage of 3D printing technique to develop repeatable means to slice bone tissues into test specimens with desired dimensions.
We will first use 3D scanning method to build a 3D virtual model of a sesamoid bone and then invert it into a CAD file for a hollow mold with hexahedral exterior. This CAD file of this virtual hexahedral mold will then be fed to a 3D printer to generate physical molds on demand. The 3D printed molds are then used for obtaining repeatable bone specimens (in terms of size and orientation) for use in future mechanical evaluation of bones.
Primary Advisor: Dr. Yinan Wei – College of Arts and Sciences – Chemistry
Co-Advisor: Dr. Dabakar Bhattacharyya – College of Engineering - Chemical and Materials Engineering
Lab Mentor: Prasangi Rajapaksha – College of Arts and Sciences – Chemistry
Cell membranes define the boundary of cells and prevent the cellular contents from diffusing away, while protecting the cell from environmental stresses and toxins. To enable selective permeability to allow material exchange while fend off harmful toxins, cell membrane is composed of a highly impermeable lipid bilayer containing protein channels and transporters to allow exchange of nutrients and waste. To mimic nature and create smart membranes, this project will use E. coli outer membrane transporter FhuA as the template to create protein channels with tailor made pore size and polarity. FhuA is involved in iron uptake in bacteria. The structure of FhuA is composed of 22 transmembrane beta-strands that form a barrel, with the N-terminal domain fold into a plug in the middle of the barrel to block leakage. We will delete the N-terminal plug domain and modify the amino acid residues lining up the inner side of the protein channel to create selective filters with tailor-made properties. Performance of the designed channels will be tested after incorporation into membrane support.
Primary Advisor: Dr. Zach Hilt – College of Engineering - Chemical & Materials Engineering
Secondary Advisor: Dr. Tom Dziubla – College of Engineering - Chemical & Materials Engineering
Lab Mentor: Trang Mai – College of Engineering – Chemical & Materials Engineering
Bisphenol A (BPA) is one of the endocrine disrupting compounds which has been widely used as raw material for the manufacture of polycarbonate, flame retardants, epoxy resins, etc. It can be found in plastic bottle, cans, food containers, adhesives and dental fillings 1-3. It has been known that BPA has an estrogenic activity which can leads to animal female precocious and hyperplasia of prostate. BPA has been also reported that it can increase the occurrence of several diseases including leukemia, ovarian cancer, and embryonic malformation 1. The biodegradation of BPA by microorganism requires long times to remove BPA. The Fenton reaction with the formation of reactive oxygen species (ROS), such as hydroxyl radicals (˙OH), has been shown to be promising for the degradation of BPA. These highly reactive species will degrade BPA into carbon dioxide, water, or biodegradable by-products 3. It has been shown that iron oxide nanoparticles can produce ROS through Fenton reaction as below 4
Previous research from our lab demonstrated that the formation of ROS can be further enhanced by the application of an alternating magnetic field (AMF) 5. This project will focus on kinetic study of BPA degradation via Fenton process induced by functionalized iron oxide nanoparticles under exposure to AMF. Other factors such as pH, initial concentration of H2O2 and particles will be also investigated.
1. W. Chen, C. Zou, Y. Liu and X. Li, Journal of Industrial and Engineering Chemistry, 2017, 56, 428-434.
2. H. Katsumata, S. Kawabe, S. Kaneco, T. Suzuki and K. Ohta, Journal of Photochemistry and Photobiology A: Chemistry, 2004, 162, 297-305.
3. M. J. Rivero, E. Alonso, S. Dominguez, P. Ribao, R. Ibañez, I. Ortiz and A. Irabien, Journal of Chemical Technology & Biotechnology, 2014, 89, 1228-1234.
4. A. M. Hauser, M. I. Mitov, E. F. Daley, R. C. McGarry, K. W. Anderson and J. Z. Hilt, Biomaterials, 2016, 105, 127-135.
5. R. J. Wydra, C. E. Oliver, K. W. Anderson, T. D. Dziubla and J. Z. Hilt, Royal Society of Chemistry Advances, 2015, 5, 18888-18893.
Primary Advisor: Dr. J. Zach Hilt – College of Engineering - Chemical and Materials Engineering
Co-Advisor: Dr. Thomas D. Dziubla – College of Engineering - Chemical and Materials Engineering
Lab Mentor: Rishabh Shah – College of Engineering - Chemical & Materials Engineering
Lab Co-Mentor: Shuo Tang – College of Engineering - Chemical & Materials Engineering
Polymeric materials have unique properties depending on the type of monomers incorporated and how they interact. The tuning of these interactions provides the potential to form polymers with a wide variety of chemical and physical properties. Temperature responsive polymers are polymers that exhibit a change in their physical properties when the temperature changes. With the inclusion of a crosslinking moiety that can be covalent or non-covalent in nature, polymers can be designed to swell in different solvents rather than dissolve. This project will investigate the swelling of non-covalently crosslinked polymer networks with N-isopropylacrylamide (NIPAAm) as the monomer backbone. NIPAAm has a unique temperature responsive property of it being hydrophilic below its lower critical solution temperature (LCST: 32ᵒC) and hydrophobic above its LCST. The different comonomers used along with NIPAAm will have a biphenyl functional group which will be utilized to form a non-covalent crosslinked network due to the pi-pi stacking interactions present between the biphenyl groups. This project will include synthesis, characterization of the polymers, swelling them in water, and characterizing their swelling properties as a function of polymer composition as well as temperature. These novel responsive materials are expected to have application in biomedical and environmental fields.
Primary Advisor: Dr. Folami Ladipo – Chemistry Department
Co-Advisor: Dr. Barbara Knutson – College of Engineering - Chemical and Materials Engineering
Co-Advisor: Dr. Steve Rankin – College of Engineering - Chemical and Materials Engineering
Lab Mentor: Daudi Saang’onyo – Department of Chemistry
To reach the full potential of lignocellulosic biomass as a renewable resource for fuels and chemicals production, efficient processes must be developed to convert lignin and cellulosic biomass into small molecules that can be upgraded into fuel and/or chemicals streams. Glucose is the most abundant monosaccharide in cellulosic biomass hence the development of efficient catalytic processes for its conversion into chemicals and biofuels is highly desired. Glucose dehydration is a promising method for the synthesis of 5-hydroxymethylfurfural (HMF), an emerging bio-derived platform chemical that potentially could be used to produce a wide variety of high-value chemicals. We have found that aluminum complexes that contain easily modified bidentate (aminomethyl)phenolate ligands are very promising catalysts in ionic liquid (IL) solvents for glucose conversion into HMF (G2H reaction). However, the use of ILs as bulk solvents has some significant drawbacks, including challenges with recovery of nonvolatile, polar solutes (such as our Al catalysts), reuse of some ILs, and their high cost. Thus, this project will investigate the reactivity of aluminum (aminomethyl)phenolate and related complexes in imidazolinum-based ILs with glucose as well as sugar model compounds such as methylglyoxal and glycoaldehyde. These studies will help to elucidate the nature of the active catalyst in G2H reaction and ligand properties best suited for creating a highly active and selective catalyst.
Primary Advisor: Dr. Daniel Pack – Colleges of Pharmacy and Engineering – Pharmaceutical Sciences and Chemical and Materials Engineering
Co-Advisor: Dr. Jason DeRouchey – College of Arts and Sciences - Chemistry
Lab Mentor: Logan Warriner – College of Engineering - Chemical & Materials Engineering
The need for safe and efficient gene delivery methods remains the primary barrier to human gene therapy. Non-viral vector materials, including polymers, can be designed to be biocompatible and non-immunogenic, but lack the efficiency to be clinically relevant. Gene therapy awaits the development of new materials that are both safe and efficient. Gene delivery polymers must be designed to perform numerous functions. In particular, the materials must bind and condense DNA to protect it from extra- and intracellular nucleases and to facilitate cellular internalization. Yet, such materials must release their DNA cargo to allow transcription. Design of more efficient materials requires understanding of polymer-DNA interactions, the formation of polymer/DNA complexes (polyplexes), and how their structures relate to intracellular trafficking and gene delivery efficiency. This project will investigate a series of zwitterion-like polymers, fabricated through modification of polyethylenimine (PEI)—a model gene delivery polymer—with succinic anhydride, that allow systematic tuning of polymer-DNA interactions. We will quantify gene delivery efficiency of these polymers and investigate their internalization and intracellular trafficking mechanisms.
Primary Advisor: Dr. Stephen Rankin – College of Engineering - Chemical & Materials Engineering
Co-Advisor: Dr. Barbara Knutson – College of Engineering - Chemical & Materials Engineering
Lab Mentor: Mr. Arif Khan – College of Engineering – Chemical & Materials Engineering
Engineered silica nanoparticles (ESNPs) are being developed at the University of Kentucky that have multiple levels of functionality required for delivery into and excretion from plant, insect and mammalian cells. ESNPs are used fairly widely in the scientific community as carriers for drugs, proteins and nucleic acids into cells – for instance to deliver small interfering RNA (siRNA) to silence the expression of targeted genes. A novel approach being pursued at UK is to use similar carriers not to only to deliver cargo, but also to harvest, at a molecular level, therapeutic compounds from living cells, such as plant cell cultures. We call this process nanoharvesting. Plants produce a number of complex small molecules to regulate their interactions with other organisms – for instance, to attract desired pollinators, to kill pathogenic fungi, or to disrupt the nervous system of pest insects. These natural products are a historically important and ongoing source of new leads for pharmaceuticals, and new advances in plant biotechnology has made available mutant strains selected to produce compounds known to target specific human receptors. This project will focus on better understanding how ESNPs are taken up within cells (for both drug delivery and nanoharvesting), and also what factors control their expulsion after uptake. Recent studies showed that a combination of transition metal and amine functionalization allows particles to be taken up in root cells and to bind active flavonoid compounds, but then to be released without causing significant harm to the plant. Here, the goal will be to visualize and quantify particle uptake into cells in culture, so that mechanisms involved in biomolecule delivery and nanoharvesting can be better understood and controlled.
Primary Advisor: Dr. Dave Puleo – College of Engineering – Biomedical Engineering
Co-Advisor: Dr. Nikita Gupta – College of Medicine - Otolaryngology
Lab Mentor: Alex Chen – College of Engineering - Biomedical Engineering
Local anesthetics are often used to block specific peripheral nerves for control of postoperative pain. Even the longer lasting local anesthetics, such as bupivacaine, have short durations and are effective for only a few hours. Approaches to prolong local analgesia include insertion of catheters for sustained infiltration and development of controlled release drug formulations. More recently, a multivesicular liposome suspension has become available for injection into joints following arthroplasty.
The objective of this project is to develop a sustained release bupivacaine delivery system for application in facial plastic and reconstructive surgical applications. Two design requirements are that the system be injectable through a small gauge needle and that it provide locally effective yet not systemically toxic concentrations of bupivacaine for at least one week. Undergraduate researcher contributions will involve formulating injectable, polymeric materials encapsulating bupivacaine, measuring drug release in vitro, and quantifying “injectability” of the system.
Primary Advisor: Dr. Eric Munson – College of Pharmacy – Pharmaceutical Sciences
Co-Advisor: Dr. Tom Dziubla – College of Engineering - Chemical and Materials Engineering
Lab Mentor: Kanika Sarpal – College of Pharmacy – Pharmaceutical Sciences
Most drug candidates under development have poor solubility. Amorphous solid dispersions are the most commonly-used approach to increase the solubility of poorly water-soluble drugs, as the solubility of the amorphous form of the drug may be up to an order of magnitude or more higher than the crystalline form of the drug. In order to minimize the likelihood that the amorphous drug will not crystallize in the formulation, polymers are added to create an intimate mixture between the drug and the polymer in an amorphous solid dispersion. This project will investigate how the stability of these amorphous solid dispersions can be probed using advanced analytical techniques. In particular, the ability to discern the crystallization tendencies of amorphous solid dispersions in a differential scanning calorimeter will be compared with phase separation as determined using solid-state NMR spectroscopy. Additional studies will take this information and show how it can be translated to functional properties such as propensity to crystallize and dissolution rate.
Primary Advisor: Prof. D. Bhattacharyya, Chemical and Materials Engineering
Co-Advisor: Prof. Yinan Wei– College of Arts and Sciences – Chemistry
Graduate student mentors: Andrew Colburn and Saiful Islam
Membranes are finding wide applications in the area of bio to water related separations. The need for creating specific surface functionality for metal capture to creating antifouling surfaces is of high importance. This project will allow synthesis and evaluation of cellulosic and other polymeric membranes. The REU student will work on: (1) membrane preparation and functionalization (2) permeability and separation studies with model compounds (3) functionalized membrane regeneration aspects. Advanced characterization will include use of zeta potential and contact angle analyzer, SEM/TEM to look at membrane structures. Andrew Colburn and Saiful Islam will be the graduate student mentors for membrane synthesis and experimental aspects.
Primary Advisor: Dr. Tom Dziubla – College of Engineering – Chemical & Materials Engineering
Co-Advisor: Dr. Zach hilt – College of Engineering – Chemical & Materials Engineering
Lab Mentor: Kelley Wiegman – College of Engineering – Chemical & Materials Engineering
Despite rapid advances in the pharmaceutical and biotechnology fields and an increase in the frequency of melanoma and other skin cancers, there have been no new sunscreen ingredients approved by the FDA in the past 20 years. Natural polyphenols, such as apigenin, quercetin and resveratrol, show high in vitro UV absorbances as well as antioxidant effects. The goal of my summer research will be to synthesize and characterize polymers of apigenin, quercetin, and resveratrol using poly (ß-amino ester).
Polymers will be synthesized by replacing the -OH groups on the polyphenols with reactive acrylate groups via acrylation by acryloyl chloride. The acrylated polyphenols will be analyzed through high performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance spectroscopy (NMR) to ensure complete reaction. After the polyphenols have been acrylated, they will be synthesized into polymer networks by reaction with an amine and an additional ‘blank’ monomer (polyethylene glycol diacrylate). Polymer networks with varying weight loadings of polyphenol will be characterized by their degradation profiles in a 7.4 pH phosphate buffer solution at standard conditions, as well as after UV-exposure to determine if UV light from the sun would impact the polymer’s effectiveness as a sunscreen ingredient. The identity of degradation byproducts will be determined through HPLC; product concentration will be analyzed through UV-visible light spectroscopy.
Primary Advisor: Jonathan Pham – College of Engineering, Chemical and Materials Engineering
Lab Mentor: Justin Glover - College of Engineering, Chemical and Materials Engineering
Biological systems are able to move at amazingly high rates that provide certain functions necessary for life. For example, some seedpods explode to disperse their seeds at a rate of ~5 m/s, to a sufficiently far distance for reproduction purposes. The accelerations can be as high as ~50x that of the fastest accelerating commercially available car. Mantis shrimps are another example of fast motion, which are able to strike the shells of their prey at ~20 m/s in a fluid, allowing them to crack open shells for feeding. Although there are fantastic demonstrations in nature, engineering fast motions in synthetic systems is a challenge. This project will explore the potential to develop fast moving structures by balancing elastic deformations of soft materials and their adhesive boundaries. This will be done by preparing model materials with different elastic moduli, characterizing their deformations, and exploring different possible boundary conditions, such as capillarity or magnetism. The results may lead to unique routes for cargo delivery containers, soft actuators, or soft robotics.