Temperature-responsive poly(N-isopropylacrylamide) (PNIPAM)/ poly(2,2,6,6-tetramethylpiperidin-1-oxyl-4-yl methacrylate) (PTMA) copolymer are synthesiszed by radical polymerization and atom transfer radical polymerization. The catalytic oxidation of alcohols to aldehydes and ketones using the NIPAM/PTMA copolymer as a catalyst was investigated. The copolymer were characterized by nuclear magnetic resonance spectroscopy, infrared spectroscopy, and gel permeation chromatography. The results of temperature-dependent UV/Vis absorption show that the lower critical solution temperature (LCST) is around 32-42 ¢J as the molecular percentage of PTMA is 0-6%. When the molecular percentage of PTMA is high than 6%, the LCST is not observed. The yield of the catalytic oxidation using the PNIPAM/PTMA copolymer as a catalyst is high than 99% within 30 min. The temperature-responsive PNIPAM/PTMA copolymer can be precipitated and purified by increasing temperature of the reaction solution higher than the LCST.

Yes / Thermal desolvation of poly(N‐isopropylacrylamide) (PNIPAM) in the presence of a low concentration of gold nanoparticles incorporates the nanoparticles resulting in suspended aggregates. By covalently incorporating <1% acenaphthylene into the polymerization feed this copolymer is enabled to be used as a model to study the segmental mobility of the PNIPAM backbone in response to gold nanoparticles both below and above the desolvation temperature, showing that there is a physical conformational rearrangement of the soluble polymer at ultralow nanoparticle loadings, indicating low affinity interactions with the nanoparticles. Thermal desolvation is capable of extracting >99.9% of the nanoparticles from their solutions and hence demonstrates that poly(N‐isopropylacrylamide) can act as an excellent scrubbing system to remove metallic nanomaterial pollutants from solution. / Science Foundation Ireland's ETS. Grant Number: 11/W.I/12085; MRC. Grant Number: MR/N501888/2

No description available.

<p>The papermaking industry uses a large amount of starch each year, both as a wet-end additive and as a rheological modifier in surface sizing and coating colors. It is important to be able to reduce the amount of chemicals used in the papermaking and surface treatment process, to reduce costs and to make the process even more efficient. Interest in new high-performance starches is great. By using these new types of starches, improved recycling of barrier products may be obtained as well as a reduction in the use of synthetic sizing agents. The objectives of this work were to understand the behavior of temperature-responsive hydrophobically modified starches, where the solubility in water simply can be adjusted by temperature or by polymer charge, to improve the barrier properties, like the water vapor permeability, mechanical properties and water resistance (Cobb and contact angle) of papers surface sized by starch-containing solutions, and to investigate the potential for industrial use of these temperature-responsive starches. It was demonstrated that the temperature-responsive starches phase separate upon cooling and, depending on the charge density of the starch, a particulate precipitation or a gel-like structure was obtained. The starch with zero net charge showed a larger increase in turbidity than the starch with a cationic net charge, indicating that particulate precipitation is favored by a zero net charge and that the formation of a gel network is favored by charged starch molecules. Further, the starches formed inclusion complexes with surfactants, giving stabilization to the starches in the presence of surfactants. The net charge density of the starch and the charge of the surfactant determined whether or not an inclusion complex would form between them. Important mechanisms for the stability of the starch seemed to be formation of mixed micellar-like structures between the hydrophobic chain of the starch and the surfactant along the starch backbone in addition to formation of inclusion complexes between the starch and the surfactant. The hydrophobically modified starches showed higher hydrophobic surface character when applied to the paper surface above the critical phase separation temperature than with application at room temperature. Free films of the temperature-responsive starches showed good barrier against oxygen, but no barrier against water vapor. The mechanical properties decreased with addition of glycerol to the films.</p>

Water remediation utilizing sorption has found strong interest due to its inexpensiveness, universal nature and ease of operation. In particular, thermo-responsive sorbents consisting of N-isopropylacrylamide (NIPAAm) offer significant potential as “smart” and advanced materials to remove multiple aqueous pollutants. NIPAAm exhibits excellent thermo-responsiveness, which senses the external temperature variation and changes its swelling and sorption behaviors in a sharp and rapid manner. At the beginning of this work, an extensive review of literature has been compiled to provide a summary of NIPAAm-based thermo-responsive sorbents in water/wastewater remediation applications. Initially, we developed a novel approach to synthesize and characterize NIPAAm copolymeric hydrogels. Four different polyphenolic crosslinkers including curcumin multiacrylate (CMA), quercetin multiacrylate (QMA), 4,4’-dihydroxybiphenyl diacrylate (44BDA) and chrysin multiacrylate (ChryMA) were successfully incorporated into crosslinked hydrogels. Their temperature responsiveness and lower critical solution temperature (LCST) were characterized using swelling studies and differential scanning calorimetry (DSC). Increasing the crosslinker content resulted in a significant decrease in the swelling ratio and LCST, which was due to the increased crosslinking and hydrophobicity introduced by the polyphenolic crosslinkers. We also demonstrated the application of two sets of aforementioned crosslinked hydrogels (NIPAAm-co-CMA and NIPAAm-co-44BDA) as effective gel sorbents to capture phenol as a model contaminant. Temperature-dependent sorption was evaluated through a binding study of phenol at 10°C and 50°C. Significant enhancement in the sorption was observed at 50°C, and this can be attributed to the phase transition induced hydrophobic interactions between the copolymer gel and phenol. Moreover, the obtained hydrogels possessed facile and efficient regeneration ability in water at 10°C, without requiring harsh solvent treatment or high energy input. Building on the sorption behavior observed with crosslinked NIPAAm hydrogels, we extended the investigation to linear copolymer systems, and these were demonstrated as a temperature responsive flocculants. Here, NIPAAm copolymers consisting of 2-phenylphenol monoacrylate (2PPMA) were successfully developed as smart flocculants to remove metal oxide nanoparticles (e.g., Fe3O4, CeO2, TiO2). The incorporation of 2PPMA enhanced the flocculation at temperatures above the LCST (e.g., 50°C), which was due to the combined hydrophobicity of 2PPMA and NIPAAm. Overall, NIPAAm-based sorbents have a variety of applications in aqueous pollutant removal and are a promising class of materials for cost-effective water remediation technology.

The papermaking industry uses a large amount of starch each year, both as a wet-end additive and as a rheological modifier in surface sizing and coating colors. It is important to be able to reduce the amount of chemicals used in the papermaking and surface treatment process, to reduce costs and to make the process even more efficient. Interest in new high-performance starches is great. By using these new types of starches, improved recycling of barrier products may be obtained as well as a reduction in the use of synthetic sizing agents. The objectives of this work were to understand the behavior of temperature-responsive hydrophobically modified starches, where the solubility in water simply can be adjusted by temperature or by polymer charge, to improve the barrier properties, like the water vapor permeability, mechanical properties and water resistance (Cobb and contact angle) of papers surface sized by starch-containing solutions, and to investigate the potential for industrial use of these temperature-responsive starches. It was demonstrated that the temperature-responsive starches phase separate upon cooling and, depending on the charge density of the starch, a particulate precipitation or a gel-like structure was obtained. The starch with zero net charge showed a larger increase in turbidity than the starch with a cationic net charge, indicating that particulate precipitation is favored by a zero net charge and that the formation of a gel network is favored by charged starch molecules. Further, the starches formed inclusion complexes with surfactants, giving stabilization to the starches in the presence of surfactants. The net charge density of the starch and the charge of the surfactant determined whether or not an inclusion complex would form between them. Important mechanisms for the stability of the starch seemed to be formation of mixed micellar-like structures between the hydrophobic chain of the starch and the surfactant along the starch backbone in addition to formation of inclusion complexes between the starch and the surfactant. The hydrophobically modified starches showed higher hydrophobic surface character when applied to the paper surface above the critical phase separation temperature than with application at room temperature. Free films of the temperature-responsive starches showed good barrier against oxygen, but no barrier against water vapor. The mechanical properties decreased with addition of glycerol to the films.

Many important therapeutic agents are associated with significant undesired side effects which often limit treatment duration and dosing. Specifically, most major classes of antitumor chemotherapeutics have deleterious effects on cell division and DNA synthesis throughout the body due to systemic biodistribution. Engineering systems for controlled drug delivery allows for improved quality of life during treatment; as well as higher localized therapeutic concentrations by isolating toxic drugs used in many diseases to specific physiological compartments. An important drug delivery strategy for controlled release of therapeutics is based on responsive polymer matrices, which undergo swelling transitions in response to environmental stimuli. Biologically relevant factors which may trigger the release of therapeutics from responsive polymers include pH, ionic strength, and temperature. Temperature responsive polymers integrated into a composite system with metal nanoparticles allow for on demand drug release via an externally-applied optical or magnetic energy source. The intent of this work was to develop a temperature-responsive drug delivery platform for controlled therapeutic release, as well to expand the toolbox for rational design of responsive hydrogel nanoparticles intended for therapeutic delivery. Temperature-responsive hydrogels were synthesized and examined in the form of nanoparticles and bulk polymer networks. These materials are based on interpenetrating polymer networks (IPNs) of polyacrylamide (PAAm) and poly(acrylic acid) (PAA), which exhibit a positive volume swelling response with respect to temperature. Since this system responds to pH, ionic strength, and temperature, these IPNs were characterized over a wide range of solution conditions. Critical synthesis parameters needed to optimize thermal responses for specific solution conditions were identified, as were the specific effects of pH and ionic strength on network swelling and stability. The reverse emulsion process used to synthesize IPN nanoparticles was characterized to determine how particle growth proceeds during preparation. To enhance biocompatibility, IPN nanoparticles were surface-modified with a corona of poly(ethylene glycol) to reduce protein adsorption, a common strategy to improve in vivo performance. Due to the large amounts of surfactants employed in the preparation of IPN nanoparticles, purification methods needed to improve safety of IPN nanoparticles were optimized, and studied in vitro to ensure cellular compatibility. / text

Scaffold based tissue reconstruction inherently limits regenerative capacity due to inflammatory response and limited cell migration. In contrast, scaffold-free methods promise formation of functional tissues with both reduced adverse host reactions and enhanced integration. Cell-sheet engineering is a well-known bottom-up tissue engineering approach that allows the release of intact cell sheet from a temperature responsive polymer such as poly-N-isopropylacrylamide (pNIPAAm). pNIPAAm is an ideal template for culturing cell sheets because it undergoes a sharp volume-phase transition owing to the hydrophilic and hydrophobic interaction around its lower critical solution temperature (LCST) of 32°C, a temperature close to physiological temperature. Compared to enzymatic digestion via trypsinization, pNIPAAm provides a non-destructive approach for tissue harvest which retains its basal surface extracellular matrix and preserves cell-to-cell junctions thereby creating an intact monolayer of cell sheet suitable for tissue transplantation. The overall thrust of this dissertation is to gain a comprehensive understanding of how tissue precursors are formed, harvested and printed from interactions with shape-changing pNIPAAm hydrogel. A simple geometrical microbeam pattern of pNIPAAm structures covalently bound on glass substrates for culturing mouse embryonic fibroblast and skeletal myoblast cell lines is presented. In order to characterize the cell-surface interactions, three main investigations were conducted: 1) the mechanism of cell detachment; 2) the feasibility of micro-contact printing tissue precursors onto target surfaces; and 3) the assembly of these tissues into three-dimensional (3D) constructs. Detachment of cells from the shape-changing hydrogel was found to correlate with the lateral swelling of the microbeams, which is induced by thermal activation, hydration and shape distortion of the patterns. The mechanism of cell detachment was primarily driven by strain, which occurred almost instantaneously above a critical strain of 25%. This shape-changing pNIPAAm construct allows water penetration from the periphery and beneath the attached cells, providing rapid hydration and detachment within seconds. Cell cultured microbeams were used as stamps for micro-contact printing of tissue precursors and their viability, metabolic activity, local and global organization were evaluated after printing. The formation and printing of intact tissues from the shape-changing hydrogel suggests that the geometric patterning of pNIPAAm directs spatial organization through physical guidance cues while preserving cell functioning. Tissue precursors were sequentially assembled into parallel and perpendicular configurations to demonstrate the feasibility of constructing dense tissues with different organizations such as interconnected cell lines that could induce vascularization to solve perfusion issues in regenerative therapies. The novel approach presented in this dissertation establishes an efficient method for harvesting and printing of tissue precursors that may be applicable for the modular, bottom up construction of complex tissues for organ models and regenerative therapies.

abstract: Following diagnosis of a glioblastoma (GBM) brain tumor, surgical resection, chemotherapy and radiation together yield a median patient survival of only 15 months. Importantly, standard treatments fail to address the dynamic regulation of the brain tumor microenvironment that actively supports tumor progression and treatment resistance. Moreover, specialized niches within the tumor microenvironment maintain a population of highly malignant glioblastoma stem-like cells (GSCs). GSCs are resistant to traditional chemotherapy and radiation therapy and are likely responsible for near universal rates of tumor recurrence and associated morbidity. Thus, disrupting microenvironmental support for GSCs could be critical to more effective GBM therapies. Three-dimensional (3D) culture models of the tumor microenvironment are powerful tools for identifying key biochemical and biophysical inputs that may support or inhibit malignant behaviors. Here, we developed synthetic poly(N-isopropylacrylamide-co-Jeffamine M-1000® acrylamide) or PNJ copolymers as a model 3D system for culturing GBM cell lines and low-passage patient-derived GSCs in vitro. These temperature responsive scaffolds reversibly transition from soluble to insoluble in aqueous solution by heating from room temperature to body temperature, thereby enabling easy encapsulation and release of cells in a 3D scaffold. We also designed this system with the capacity for presenting the cell-adhesion peptide sequence RGD for adherent culture conditions. Using this system, we identified conditions that promoted GBM proliferation, invasion, GSC phenotypes, and radiation resistance. In particular, using two separate patient-derived GSC models, we observed that PNJ scaffolds regulated self-renewal, provided protection from radiation induced cell death, and may promote stem cell plasticity in response to radiation. Furthermore, PNJ scaffolds produced de novo activation of the transcription factor HIF2α, which is critical to GSC tumorigenicity and stem plasticity. All together, these studies establish the robust utility of PNJ biomaterials as in vitro models for studying microenvironmental regulation of GSC behaviors and treatment resistance. / Dissertation/Thesis / Doctoral Dissertation Biomedical Engineering 2017

ABSTRACT Effective drug delivery to ocular tissues is an unmet challenge that has significant potential to improve the treatment of ocular diseases. Whether the intended drug delivery target is the anterior or posterior segment, the eye’s efficient natural protection mechanisms prevent effective and sustained drug delivery. Anatomical and physiological barriers including the rapid tear turnover that effectively washes away topically applied drugs, the impermeable characteristics of the cornea, conjunctiva, and sclera, and the tight junctions in the blood-ocular barriers make conventional drug delivery methods ineffective. New materials that are able to overcome these barriers are essential to improving the sustained delivery of ophthalmic therapeutics to the intended targets within the eye. This thesis will explore two polymeric drug delivery systems that have the potential to improve therapeutic delivery to ocular tissues. Chapter 1 will discuss the anatomical and physiological barriers to ophthalmic drug delivery and overview current research in this area. Chapter 2 will discuss the synthesis of N-isopropylacrylamide-based copolymers with adjustable gelation temperatures based on composition and molecular weight. Chapter 3 will discuss further development of these copolymers into an injectable, thermoresponsive, and resorbable polymeric drug delivery system intended for the treatment of diseases in the posterior segment. Chapter 4 will discuss the development of mucoadhesive polymeric micelle nanoparticles based on phenylboronic acid intended for topical administration of ophthalmic therapeutics. Finally, Chapter 5 will provide an overview of potential future work on these materials that could further develop and broaden their therapeutic use. / Thesis / Master of Science in Biomedical Engineering