Browsing by Author "Popat, Ketul C., committee member"

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Open Access
Biopolymer nanomaterials for growth factor stabilization and delivery
(Colorado State University. Libraries, 2014) Place, Laura Walker, author; Kipper, Matt J., advisor; James, Susan, committee member; Popat, Ketul C., committee member; Miller, Benjamin, committee member
Biopolymers are useful in tissue engineering due to their inherent biochemical signals, including interactions with growth factors. There are six biopolymers used in this work, the glycosaminoglycans (GAGs), heparin (Hep), chondroitin sulfate (CS), and hyaluronan (HA), chitosan (Chi), a GAG-like molecule derived from arthropod exoskeletons, a Chi derivative N,N,N¬-trimethyl chitosan (TMC), and an extracellular matrix (ECM)-derived material, demineralized bone matrix (DBM). The direct delivery of growth factors is complicated by their instability. GAG side chains of proteoglycans stabilize growth factors. GAGs also regulate growth factor-receptor interactions at the cell surface. The majority of proteoglycan function is derived from its GAG side chain composition. Here we report the development of nanoparticles, proteoglycan-mimetic graft copolymers, incorporation of nanoparticles into electrospun nanofibers, and processing methods for electrospinning demineralized bone matrix to fabricate bioactive scaffolds for tissue engineering. The nanoparticles were found to show similar size, composition, and growth factor binding and stabilization as the proteoglycan aggrecan. We use basic fibroblast growth factor (FGF-2) as a model heparin-binding growth factor, demonstrating that nanoparticles can preserve its activity for more than three weeks. Graft copolymers were synthesized with either CS or Hep as the side chains at four different grafting densities. Their chemistry was confirmed via ATR-FTIR and proton NMR. They were shown to increase in effective hydrodynamic diameter with grafting density, resulting in a size range from 90-500 nm. Graft copolymers were tested for their ability to deliver FGF-2 to cells. The CS conditions and the Hep 1:30 performed equally as well as when FGF-2 was delivered in solution. Preliminary dynamic mechanical testing demonstrated that hydrogels containing the copolymers exhibit changes in compressive modulus with cycle frequency. Two electrospinning techniques were developed, using an emulsion and a coaxial needle, for incorporating growth factor into electrospun nanofibers. We bound FGF-2 to aggrecan-mimetic nanoparticles for stabilization throughout electrospinning. The two techniques were characterized for morphology, nanoparticle and FGF-2 incorporation, cytocompatibility, and FGF-2 delivery. We demonstrated that both techniques result in nanofibers within the size range of collagen fiber bundles and dispersion of PCNs throughout the fiber mat, and exhibit cytocompatibility. We determined via ELISA that the coaxial technique is superior to the emulsion for growth factor incorporation. Finally, FGF-2 delivery to MSCs from coaxially electrospun nanofibers was assessed using a cell activity assay. We developed a novel method for tuning the nanostructure of DBM through electrospinning without the use of a carrier polymer. This work surveys solvents and solvent blends for electrospinning DBM. The effects of DBM concentration and dissolution time on solution viscosity are reported and correlated to observed differences in fiber morphology. We also present a survey of techniques to stabilize the resultant fibers with respect to aqueous environments. Glutaraldehyde vapor treatment is successful at maintaining both macroscopic and microscopic structure of the electrospun DBM fibers. Finally, we report results from tensile testing of stabilized DBM nanofiber mats, and preliminary evaluation of their cytocompatibility. The DBM nanofiber mats exhibit good cytocompatibility toward human dermal fibroblasts (HDF) in a 4-day culture.
Open Access
Development of a hierarchical electrospun scaffold for ligament replacement
(Colorado State University. Libraries, 2018) Pauly, Hannah Marie, author; Haut Donahue, Tammy L., advisor; Easley, Jeremiah, committee member; Kelly, Daniel J., committee member; Palmer, Ross, committee member; Popat, Ketul C., committee member
The anterior cruciate ligament (ACL) is a dense collagenous structure that connects the femur to the tibia and is vital for joint stability. The ACL possesses complex time-dependent viscoelastic properties and functions primarily to prevent excessive translations and rotations of the tibia relative to the femur. It is estimated that 400,000 ACL tears occur in the United States annually and the monetary burden of these injuries and their subsequent treatment is approximately $1 billion annually. After injury allografts and autografts are commonly implanted to reconstruct the torn ACL in an attempt to restore joint stability, prevent pain, and limit damage to surrounding tissues. However surgical reconstructions fail to completely restore knee functionality or prevent additional injury and regardless of intervention technique radiographic osteoarthritis is present in 13% of patients 10 years after ACL rupture. Drawbacks to traditional treatments for ACL ruptures motivate the development of a synthetic ACL replacement. Tissue engineering is the use of a scaffold, cells, and signaling molecules to create a replacement for damaged tissue. The goal of this work is to develop a polymer scaffold that can be utilized as a replacement for the ACL. A tissue engineered ACL replacement should replicate the hierarchical structure of the native ACL, possess reasonable time zero mechanical properties, and promote the deposition of de novo collagenous tissue in vitro. Additionally, the scaffold should be implantable using standard surgical techniques and should maintain in situ tibiofemoral contact mechanics. Thus, four specific aims are proposed: 1) Fabricated and characterize an aligned 3-dimensional electrospun scaffold for ACL replacement. 2) Assess the in vitro behavior of ovine bone marrow-derived stems cells seeded on the scaffold in the presence of conjugated growth factor. 3) Evaluate the performance of the electrospun scaffold using uniaxial mechanical testing. 4) Assess the effect of the electrospun scaffold on ovine stifle joint contact mechanics. Development of a tissue engineered ACL replacement that mimics the structure and function of the native ACL would provide a novel treatment to improve outcomes of ACL injuries.
Open Access
Engineering effective fibrocartilage replacement technologies using nanostructure-driven replication of soft tissue biomechanics in thermoplastic elastomer hydrogels
(Colorado State University. Libraries, 2018) Lewis, Jackson Tyler, author; Bailey, Travis S., advisor; Haut Donahue, Tammy L., advisor; James, Susan P., committee member; Popat, Ketul C., committee member; Li, Yan, committee member
Synthesis of hydrogel networks capable of accurately replicating the biomechanical demands of musculoskeletal soft tissues continues to present a formidable materials science challenge. Current systems are hampered by combinations of limited moduli at biomechanically relevant strains, inefficiencies driven by undesirable hysteresis and permanent fatigue, and recovery dynamics too slow to accommodate rapid cycling prominent in most biomechanical loading profiles. This dissertation presents a new paradigm in hydrogel design based on prefabrication of an efficient nanoscale network architecture using the melt-state self-assembly of amphiphilic block copolymers. Rigorous characterization and preliminary mechanical testing reveal that swelling of these preformed networks produce hydrogels with physiologically relevant moduli and water compositions, negligible hysteresis, sub-second elastic recovery rates, and unprecedented resistance to fatigue over hundreds of thousands of compressive cycles. By relying only on simple thermoplastic processing to form these nanostructured networks, the synthetic complexities common to most solution-based hydrogel fabrication strategies are completely avoided. Described within this dissertation are a range of efforts, broadly focused on refining synthetic and post-synthetic processing techniques to improve the modulus, surface hydrophilicity, fatigue resistance and cytocompatibility of these thermoplastic elastomer hydrogels, with the ultimate goal of producing a material viable as a meniscal replacement.
Open Access
From meniscus to bone: structure and function of human meniscal entheses and deleterious effects of osteoarthritis
(Colorado State University. Libraries, 2013) Abraham, Adam Christopher, author; Haut Donahue, Tammy L., advisor; Kaufman, Kenton R., committee member; Puttlitz, Christian M., committee member; Popat, Ketul C., committee member; Goodrich, Laurie R., committee member
Knee osteoarthritis plagues millions of people in the U.S. alone, yet the mechanisms of initialization are not well understood. Recent work suggests that there are a myriad of potential disease inducing routes that may give rise to this debilitating condition. Understanding and elucidating the potential pathways leading to osteoarthritis may result in novel methods of prevention and/or treatment. Human meniscus are C-shaped fibrocartilaginous structures contained within the diathroidal knee joint, the primary function of which are to provide support and lubrication between the femur and the tibia. Each knee incorporates two menisci, lateral and medial, affixed at the anterior and posterior attachment sites to the tibial plateau. Meniscal attachments, or entheses, are unique graded tissue interfaces comprised of four distinct zones that diffuse longitudinal loads transmitted via hoop stresses of collagen fibrils in the meniscal body. The attachments must remain firmly rooted to the tibial plateau to effectively attenuate joint loads. If the attachments become structurally compromised, either through direct or indirect means, excessive transverse meniscal translation results. Such joint extrusion of the meniscal body is a known precursor to developing osteoarthritis. To date there have been no investigations of integrity of meniscal attachments in the aged arthritic knee. A proposed treatment modality for meniscus degeneration is engineered replacements which focus solely on the meniscal body, disregarding the specialized tissue interface. However, the efficacy of these replacements likely remains dependent on restoring the meniscus to bone transition. Previous literature has shown that each meniscal attachment is biochemically and mechanically unique and thus should be independently examined. Therefore, the overall goal of this work is to examine the loading environment of each attachment in both a healthy and injured knee, as well as characterize the structure-function relationship. This knowledge can then be utilized to develop novel preventative strategies in order to deter the onset of osteoarthritis, thereby reducing the burden on individuals as they age. Therefore, the goal of this work was to: • Determine the transverse mechanical properties of the attachment sites and couple with current literature to aid in numerical modeling • Determine the native loading environment for each attachment under physiological and pathlogical loading conditions • Examine the structure and function of the native attachment sites • Examine the deleterious effects of osteoarthritis on the attachment sites.
Open Access
Hyaluronic acid enhancement of expanded polytetrafluoroethylene for small diameter vascular grafts
(Colorado State University. Libraries, 2014) Lewis, Nicole R., author; James, Susan P., advisor; Popat, Ketul C., committee member; Bailey, Travis, committee member
Cardiovascular disease is the leading cause of mortality and morbidity in the United States and other developed countries. In the United States alone, 8 million people are diagnosed with peripheral arterial disease per year and over 250,000 patients have coronary bypass surgery each year. Autologous blood vessels are the standard graft used in small diameter (<6mm) arterial bypass procedures. Synthetic small diameter grafts have had limited success. While polyethylene (Dacron) and expanded polytetrafluoroethylene (ePTFE) are the most commonly used small diameter synthetic vascular graft materials, there are significant limitations that make these materials unfavorable for use in the low blood flow conditions of the small diameter arteries. Specifically, Dacron and ePTFE grafts display failure due to early thrombosis or late intimal hyperplasia. With the shortage of tissue donors and the limited supply of autologous blood vessels available, there is a need for a small diameter synthetic vascular graft alternative. The aim of this research is to create and characterize ePTFE grafts prepared with hyaluronic acid (HA), evaluate thrombogenic potential of ePTFE-HA grafts, and evaluate graft mechanical properties and coating durability. The results in this work indicate the successful production of ePTFE-HA materials using a solvent infiltration technique. Surface interactions with blood show increased platelet adhesion on HA-modified surfaces, though evidence may suggest less platelet activation and erythrocyte lysis. Significant changes in mechanical properties of HA-modified ePTFE materials were observed. Further investigation into solvent selection, uniformity of HA, endothelialization, and dynamic flow testing would be beneficial in the evaluation of these materials for use in small diameter vascular graft bypass procedures.
Open Access
Improving hydrophilicity of silicone elastomer by IPN formation with hyaluronan
(Colorado State University. Libraries, 2016) Koch, Richard L., author; James, Susan P., advisor; Bailey, Travis, committee member; Popat, Ketul C., committee member
Soft contact lenses have been available to consumers for the past several decades. By far, the most popular form on the market today is the silicone hydrogel, with nearly 70% of the market share. However, many contact lens wearers still have issues which cause them to discontinue lens use. It is estimated that between 25-35% of people discontinue use permanently. This can be traced back to two main issues with modern hydrogel lenses: a lack of adequate oxygen permeability across the lens; and lens-induced dehydration of the cornea. The corneal epithelium lining the lens of the eye is an avascular environment. As such, the cells must get their oxygen by diffusion through the tear film, or any material covering the lens. The silicone hydrogel SCLs have reduced oxygen gas permeability compared to traditional silicone elastomers. Additionally, when the hydrogel lenses lose water to evaporation, they pull water from the wearer's eye, contributing to dryness. Beyond simple discomfort, these issues can lead to pathologies such as hyperemia and even corneal cell death in severe cases. It was determined that a solution to these issues would be a new ocular lens material which had superior oxygen gas permeability and was hydrophilic without containing water in its bulk. The aim of this research was to create an interpenetrating polymer network (IPN) materials of poly(dimethyl siloxane) (PDMS) and hyaluronan (HA) with such properties. The results in this work indicate the successful synthesis of these HA-PDMS IPN materials. These elastomeric materials had improved hydrophilicity compared to untreated PDMS. Additionally, new chemical species (ATR/FTIR and XPS spectroscopy) and surface morphologies (SEM imaging) indicated the introduction of HA into the PDMS. Furthermore, analysis of the oxygen gas permeability showed no significant change for the treated samples as compared to the PDMS base material. As silicone materials have use in many biomedical fields, the material was also tested for platelet adhesion/activation and whole blood clotting. However, studies showed unfavorable results as the treated samples still caused platelet activation and blood clotting. Additionally, overall optical transmittance of the treated materials was significantly decreased. Further refinement of the treatment methods may yield more favorable results in the areas of thrombogenicity and platelet adhesion.
Open Access
Improving thin-film polycrystalline CdSeTe/CdTe solar cell efficiencies through statistical design of experiments
(Colorado State University. Libraries, 2022) Lustig, Zachary F., author; Sampath, Walajabad S., advisor; Sites, James R., committee member; Popat, Ketul C., committee member
In recent decades, cadmium telluride (CdTe) solar photovoltaic (PV) technology has become increasingly popular to meet global energy demands. Its high throughput industrial fabrication methods, low material usage, recyclability, longevity, and theoretical maximum efficiency have led to its widespread integration in the PV sector. Most of the CdTe PV research reported in literature utilizes one-factor-at-a-time (OFAT) experiments. This work leverages statistical design of experiments (DOE) and statistical analysis of data to study the relationships between multiple processing factors and solar cell performance metrics. OFAT only indicates the primary effect of the chosen variable, whereas DOE determines the primary effect as well as the interaction effects. DOE determines both critical and insignificant factors, whereas OFAT assumes everything is a critical factor. DOE also requires fewer experiments, has more sophisticated predictive capabilities, and streamlines process optimization in comparison to OFAT. Since DOE is most effective with large data sets, the unique high throughput capability of the Advanced Research Deposition System (ARDS) at Colorado State University makes our lab a perfect candidate to utilize DOE for CdTe solar cell research. In this study, DOE and statistical analysis were used to investigate copper (Cu) doping, electrode painting, absorber deposition rate and temperature, p-doping of CdSe0.4Te0.6 (CST40) through arsenic (As) incorporation and tellurium (Te) overpressure, and oxide deposition at the back of the cell. Multiple linear regression (MLR) and analysis of variance (ANOVA) were conducted on all DOE's. An improved process was identified for the baseline high efficiency Cu-doped solar cells in which total process time was reduced by 33%. A thick 6µm structure of 18.5%+ efficiency was developed following statistical model suggestions. A standard procedure for electrode painting was developed. As a result of DOE, several 19%+ cells were fabricated achieving the highest efficiency of 19.44%. The best performing As doped CST40 graded CdTe cells of 18.5%+ were also fabricated using these methods. Carrier concentration versus voltage plots indicated successful p-doping of CST40 with As. Annealing the absorber with cadmium arsenide (Cd3As2) and depositing tellurium oxide (TeOx) at the back of the cell improved performance, yielding 80%+ fill factors. Decreasing thickness of CdTe behind CST40:As increased short-circuit current density to 30 mA/cm2+. Lastly, thinner absorbers yielded higher performance when backed with NiO:Cu.
Open Access
Investigation of Group V doping and passivating oxides to reduce the voltage deficit in CdTe solar cells
(Colorado State University. Libraries, 2022) Danielson, Adam H., author; Sampath, W. S., advisor; James, Susan P., committee member; Popat, Ketul C., committee member; Sites, James R., committee member
Thin film cadmium telluride is one of the most successful photovoltaic technologies on the market today. Second only to silicon in yearly output and accounting for 40% of U.S. utility-scale photovoltaic installation, CdTe is known for its ease of manufacture, ideal bandgap, and low levelized cost of energy. Despite its commercial success, CdTe underperforms compared to its theoretical potential. The current world record CdTe device is only 21.0% compared to a theoretical maximum of 33.1%. This significant discrepancy in efficiencies can mostly be attributed to the poor open-circuit voltage of CdTe devices. Compared to silicon technologies, CdTe has a large voltage deficiency, exceeding 250 mV. While copper doping has traditionally been used for CdTe devices, it has proven to be incapable of sufficiently doping CdTe. Copper typically dopes CdTe in the 1014 to 1015 holes/cm3 range where most models predict that 1016–1017 is needed. Additionally, interstitial copper is a fast diffuser in CdTe, and can lead to numerous stability issues. As an alternative to copper, this work explores arsenic as a dopant for CdTe. Using a novel arsenic doping technique, hole concentrations greater than 1015 cm-3, microsecond lifetimes, and increased radiative efficiency are achieved. These are important prerequisites to achieving higher voltages. Achieving high doping levels alone is not sufficient to achieve higher device performance. A well-passivated and carrier selective contact is needed to ensure that electron-hole pairs do not recombine and are extracted as useable energy. Aluminum oxide has been shown to passivate CdTe surfaces. This work illustrates the explorations of using Al2O¬3 as a passivation layer, pairing it with highly doped amorphous silicon as a hole contact, resulting in excess-carrier lifetimes up to 8 µs, the highest reported to date for polycrystalline Cd(Se)Te. Although the inclusion of arsenic doping and an aluminum oxide back contact are each explored separately, the combination of both methods result in massive improvements to the carrier lifetime, interface passivation and radiative efficiency. Through this combination, microsecond lifetime and External Radiative Efficiency of over 4% are achieved. The excellent ERE values measured here are indicative of large quasi-Fermi level splitting, leading to an implied voltage with multiple device structures of nearly 1 V and an implied voltage of 25%. Finally, while CdSeTe serves as a more promising photovoltaic absorber candidate compared to CdTe, certain difficulties remain which must be addressed. Careful selection of processing conditions is shown to create a dense and large-grained film while eliminating wurtzite-phase crystal growth, which has been shown to degrade device performance. Surprisingly, as-deposited CdSeTe is shown to be n-type or nearly intrinsic rather than the previously supposed p-type. This necessitates additional steps to account for very poor hole conductivity, which can produce zero-current devices if not addressed. Challenges notwithstanding, CdSeTe absorbers are shown to be a key component in devices capable of a photovoltaic conversion efficiency of greater than 25%.
Open Access
Optimization of a centrifugal electrospinning process using response surface methods and artificial neural networks
(Colorado State University. Libraries, 2014) Greenawalt, Frank E., author; Duff, William S., advisor; Bradley, Thomas H., committee member; Labadie, John W., committee member; Popat, Ketul C., committee member
For complex system designs involving a large number of process variables, models are typically created for evaluating the system behavior for various operating conditions. These models are useful in understanding the effect that various process variables have on the process response(s). Design of Experiments (DOE) and Response Surface Methodology (RSM) are typically used together as an effective approach to optimize a process. RSM and DOE commonly employ first and second order algebraic models. Artificial Neural Networks (ANN) is a more recently developed modeling approach. An evaluation of these three approaches is made in conjunction with experimentation on a newly developed centrifugal electrospinning prototype. The centrifugal electrospinning process is taken from the exploratory design phase through the pre-production phase to determine optimized manufacturing operating conditions. Centrifugal Electrospinning is a sub platform technology to electrospinning for producing nanofibrous materials with a high surface to volume ratio, significant fiber interconnectivity and microscale interstitial spaces. [131] Centrifugal electrospinning is a potentially more cost effective advanced technology which evolved from traditional electrospinning. Despite there being a substantial amount of research in centrifugal electrospinning, there are still many aspects of this complex process that are not well understood. This study started with researching and developing a functional centrifugal electrospinning prototype test apparatus which, through patent searches, was found to be innovative in nature. Once a functional test apparatus was designed, an exploration of the process parameter settings was conducted to locate an experimental setup condition where the process was able to produce acceptable sub-micron polymeric fibers. At this point, the traditional RSM/DOE approach was used to find a setting point that produced a media efficiency value that was close to optimal. An Artificial Neural Network architecture was then developed with the goal of building a model that accurately predicts response surface values. The ANN model was then used to predict responses in place of experimentation on the prototype in the RSM/DOE optimization process. Different levels of use of the ANN were then formulated using the RSM/DOE and ANN to investigate its potential advantages in terms of time, and cost effectiveness to the overall optimization approach. The development of an innovative centrifugal electrospinning process was successful. A new electrospinning design was developed from the research. A patent application is currently pending on the centrifugal electrospinning applicator developed from this research. Near optimum operating settings for the prototype were found. Typically there is a substantial expense associated with evolving a well-designed prototype and experimentally investigating a new process. The use of ANN with RSM/DOE in the research was seen to reduce this expense while identifying settings close to those found when using RSM/DOE with experimentation alone. This research also provides insights into the effectiveness of the RSM/DOE approach in the context of prototype development and provides insights into how different combinations of RSM/DOE and ANN may be applied to complex processes.
Open Access
Passivation studies on Cd0.6Zn0.4Te films using CdCl2, MgCl2 and ZnCl2 for top cell application in a multijunction solar cell
(Colorado State University. Libraries, 2018) Shimpi, Tushar M., author; Sampath, W. S., advisor; Sites, James R., committee member; Kota, Arun K., committee member; Popat, Ketul C., committee member
Passivation treatment with the chloride compounds is an important step in the fabrication of II-VI solar cells for improving the device performance. In cadmium telluride solar cells, cadmium chloride passivation treatment incorporates chlorine along the grain boundaries and helps in recrystallization, grain growth, removal of stacking faults and doping grain boundaries as n-type. In cadmium zinc telluride solar cells, the retention of zinc after the cadmium chloride passivation treatment is one of the challenges incurred in fabricating the top cell in a multijunction solar cell. During the passivation treatment, the loss of zinc occurs in the form of volatile zinc chloride compound. The depletion or complete loss of zinc reduces the higher band gap ternary alloy into lower band gap binary compound of CdTe. This impedes the purpose of fabricating a high band gap top cell in a multijunction solar cell. The focus of this study is on passivating Cd0.6Zn0.4Te (CdZnTe) films using three different chloride compounds separately and understanding the effects by studying the material properties of the passivated films and electrical performance of the fabricated devices. In the preliminary experiments, CdZnTe films were deposited by RF sputtering from a single target. Initial characterization of CdZnTe films deposited on plain glass indicated that the films had a strong preferred orientation along {111} plane with a band gap of ~1.72eV. In the cadmium chloride passivation treatment, loss of zinc from the surface and no chlorine along the grain boundaries was observed from transmission electron microscope images and X ray diffraction measurements. No loss of zinc was observed after the magnesium chloride and zinc chloride passivation treatments. Increase in the grain size of the CdZnTe films after magnesium chloride treatment and decrease of the preferred orientation after zinc chloride treatment were the benefits of the individual passivation treatments. Modifying the test structure by adding a cadmium telluride film as a capping layer on the back of RF sputtered CdZnTe and then carrying out the cadmium chloride passivation treatment helped in retaining the zinc. Heavy diffusion of zinc into cadmium sulphide due to cadmium telluride deposition at high temperature and difficulty to isolate the photo current generated by cadmium telluride were few drawbacks of this test structure. Based on the insights gained from the preliminary experiments, two sets of experiments were conducted. In the first set, cadmium sulphide cap as a barrier was deposited on the back of RF sputtered CdZnTe and co-sublimated cadmium telluride and zinc films with a band gap of 1.72 eV. The bulk composition was maintained after the cadmium chloride passivation treatment in the films deposited by both the methods. However the device performance of co-sublimated films was better than the RF sputtered CdZnTe devices. The transmission electron image obtained from the cross section of co-sublimated film fitted with cadmium sulphide cap and then treated with cadmium chloride showed presence of chlorine along the grain boundaries. The zinc chloride passivation treatments with higher substrate temperature compared to the source were the second set of experiments. The zinc loss from RF sputtered CdZnTe films after the cadmium chloride treatment did not occur. The fabricated devices exhibited diode like behavior. The images under scanning electron microscopy showed that the grain size did not increase after the zinc chloride treatment.
Open Access
The effects of salt on the lower critical solution temperatures of Poly (N-isopropylacrylamide) and its copolymer studied from molecular dynamics simulations
(Colorado State University. Libraries, 2011) Du, Hongbo, author; Qian, Xianghong, advisor; James, Susan P., committee member; Popat, Ketul C., committee member; Wickramasinghe, S. Ranil, committee member
Classical molecular dynamics (MD) simulations were performed to investigate the effects of salt on the lower critical solution temperature (LCST) of Poly (N-isopropylacrylamide) (PNIPAM). PNIPAM is often studied as a protein proxy due to the presence of a peptide bond in its monomer unit. PNIPAM is a temperature sensitive polymer which exhibits hydrophobic-hydrophilic phase transition at its LCST. The presence of salt in the solution will shift its LCST, typically to a lower temperature. This LCST shift follows the so-called Hofmeister series. MD simulations of PNIPAM in 1 M NaCl, NaBr, NaI and KCl solutions were carried out to elucidate the effects of different salts on the LCST and protein stability. The simulation results suggest that direct interactions between the salt cations and the polymer play a critical role in the shift of LCST and subsequently on protein stability. Further, cations have a much stronger affinity with the polymer, whereas anions bind weakly with the polymer. Moreover, the cation-polymer binding affinity is inversely correlated with the cation-anion contact pair association constant in solution. MD simulations were also carried out for PNIPAM in 1 M mixed salt solution containing 0.5 M Na+, K+, Cl- and Br- each. The simulation results further confirmed the conclusions. Additional MD simulations were conducted for PNIPAM-co-PEGMA copolymer in 1 M NaCl solution. Interestingly, Na+ was found to form a complex with multiple O atoms on the PNIPAM-co-PEGMA chain thus greatly enhancing the cationic binding with the copolymer. These results provide significant insight into the effects of salt on protein stability.
Open Access
Tuning the interaction of droplets with liquid-repellent surfaces: fundamentals and applications
(Colorado State University. Libraries, 2018) Movafaghi, Sanli, author; Kota, Arun K., advisor; James, Susan P., committee member; Henry, Charles S., committee member; Popat, Ketul C., committee member
Liquid-repellent surfaces can be broadly classified as non-textured surfaces (e.g., smooth slippery surfaces on which droplets can slide easily) and textured surfaces (e.g., super-repellent surfaces on which liquid droplets can bead up and roll off easily). The liquid repellency of smooth slippery surfaces can be adjusted by tuning the surface chemistry. The liquid repellency of super-repellent surfaces can be adjusted by tuning the surface chemistry and surface texture. In this work, by systematically tuning the surface chemistry and surface texture and consequently the surface wettability of solid surfaces, the interaction of droplets of various liquids on liquid-repellent surfaces has been investigated. Based on this understanding, the following phenomena/applications have been investigated/developed: (i New methodology to sort liquid droplets based on their surface tension: By tuning the surface chemistry and surface texture of solid surfaces, we tuned the mobility of liquids with different surface tension on super-repellent surfaces. Utilizing this, we fabricated a simple device with precisely tailored domains of surface chemistry that can sort droplets by surface tension. (ii) New approach to detect the quality of fuel blends: By tuning the surface chemistry of solid surfaces, we investigated the interaction of fuel blends with liquid-repellent surfaces. Based on the understanding gained, we fabricated a simple, field-deployable, low-cost device to rapidly detect the quality of fuel blends by sensing their surface tension with significantly improved resolution. (iii) Novel materials with improved hemocompatibility: By systematically tuning the surface chemistry and surface texture and consequently the surface wettability of solid surfaces, we investigated the interaction of blood with super-repellent surfaces. Based on the understanding gained, we fabricated super-repellent surfaces with enhanced hemocompatibility. (iv) Advanced understanding of droplet splitting upon impacting a macroscopic ridge: By systematically tuning the ridge geometry, we investigated the interaction of impacting water droplets with super-repellent ridges. Based on the understanding gained, we demonstrated the scaling law for predicting the height from which water droplets should fall under gravity onto a super-repellent ridge for them to split into two smaller droplets.
Embargo
Zwitterionic polymeric nanoparticles for drug delivery
(Colorado State University. Libraries, 2024) Lee, Jeonghun, author; Herrera-Alonso, Margarita, advisor; Bailey, Travis S., committee member; Popat, Ketul C., committee member; Peebles, Christie, committee member
Bottlebrush block copolymers, characterized by their densely grafted side chains stemming from a highly persistent backbone, offer unique advantages for drug delivery, including enhanced micellar stability, reduced critical micelle concentration, and controlled surface topography, setting them apart from traditional linear polymers. This dissertation focuses on zwitterionic bottlebrush block copolymers (ZBCPs) composed of poly(D, L-lactide) (PLA) and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) side chains, synthesized via a combination of ring-opening and controlled radical polymerization using a grafting-from approach. ZBCPs were self-assembled into uniform spherical micelles and nanoparticles through direct dissolution and rapid mixing methods, and these self-assembled nanostructures were systematically evaluated. Compared to non-ionic PEG micelles (standard), zwitterionic bottlebrush micelles (ZBM) demonstrated superior stability under high salt conditions, elevated temperatures cycles, and in the presence of fetal bovine serum, whereas kinetically assembled nanoparticles (ZBNP) exhibited greater drug loading capacity. Both ZBM and ZBNP also showed excellent hemocompatibility, with ZBM displaying exceptional redispersibility in the absence of cryoprotectants. In parallel, this dissertation investigates boronic acid-functionalized zwitterionic polymers for drug delivery. A linear ABC-type amphiphilic copolymer containing poly(3-aminophenylboronic acid) as the central block was synthesized and compared to its non-functional counterpart. The boronic acid-containing nanoparticles exhibited pH- and oxidation-responsive behavior, enabling controlled drug release. Expanding this concept to a bottlebrush architecture, boronic acid-functionalized bottlebrush triblock copolymers were developed to further enhance nanoparticle performance. The inclusion of a boronic acid interlayer in the bottlebrushes significantly improved redispersibility of drug-loaded nanoparticles while maintaining high drug loading capacity, superior stability, and excellent hemocompatibility. This dissertation provides fundamental insights into solution-based self-assembled nanostructures derived from ZBCPs and boronic acid-functionalized polymers, establishing them as promising advanced drug delivery platforms. These systems offer tunable release kinetics, robust colloidal stability in harsh biological environments, excellent hemocompatibility, and superior redispersibility, thereby enhancing their translational potential in the field of nanomedicine.