Stimuli-responsive drug delivery materials release their payloads in response to physiological or external cues and are widely reported for stimuli such as pH, temperature, ionic strength, electrical potential, or applied magnetic field. While a handful of reports exist on materials responsive to mechanical stimuli, this area receives considerably less attention. This dissertation therefore explores three-dimensional networks and polymer-metal composites as mechanoresponsive biomaterials by using mechanical force to either trigger the release of entrapped agents or change the conformation of implants. At the nanoscale, shear is demonstrated as a mechanical stimulus for the release of a monoclonal antibody from nanofibrous, low molecular weight hydrogels formed from bio-inspired small molecule gelators. Using their self-healing, shear-thinning properties, mechanoresponsive neutralization of tumor necrosis factor alpha (TNFα) in a cell culture bioassay is achieved, suggesting utility for treating rheumatoid arthritis. Reaching the microscale, mechanical considerations are incorporated within the design of cisplatin-loaded meshes for sustained local drug delivery, which are fabricated through electrospinning a blend of polycaprolactone and poly(caprolactone-co-glycerol monostearate). These meshes are compliant, amenable to stapling/suturing, and they exhibit bulk superhydrophobicity (i.e., extraordinary resistance to wetting), which sustains release of cisplatin >90 days in vitro and significantly delays tumor recurrence in an in vivo murine lung cancer resection model. This polymer chemistry/processing strategy is then generalized by applying it to the poly(lactide-co-glycolide) family of biomedical polymers. As a macroscopic approach, a tunable, tension-responsive multilayered drug delivery device is developed, which consists of a water-absorbent core flanked by two superhydrophobic microparticle coatings. Applied strain initiates coating fracture to cause core hydration and subsequent drug release, with rates dependent on strain magnitude. Finally, macroscopic, shape-changing polymer-composite materials are developed to improve the current functionality of breast biopsy markers. This shape change provides a means to prevent marker migration from its intended site—a current clinical problem. In summary, mechanoresponsive systems are described, ranging from the nano- to macroscopic scale, for applications in drug delivery and biomedical devices. These studies add to the nascent field of mechanoresponsive biomedical materials and the arsenal of drug delivery techniques required to combat cancer and other medical ailments. / 2017-10-27T00:00:00Z

This dissertation presents the fabrication of a silicate-based nanocomposite hydrogel with outstanding shear-thinning properties, viscoelastic behaviour, and water retention capacity. Due to their adaptable mechanical properties, bioavailability, and water retention capacity, these nanocomposite hydrogels have been extensively used for biomedical applications. Laponite nanoparticles are among the most utilized silicate-based minerals. These clay nanoparticles are composed of platelets that are positively charged on the edges and negatively charged on the surface. The high aspect ratio of the polyanionic surface of the Laponite nanoparticles can absorb and trap ionic functional groups with non-covalent interactions. These silicate-based nanocomposite hydrogels are produced by dispersing Laponite nanoparticles in deionized water, forming a homogenous colloid. The uniform dispersion of these nanoparticles in aqueous solutions forms a “house of cards” structure, which eliminates particle aggregation and improves their surface interaction with ionic compounds. The fabrication process is followed by the addition of the stable colloid to various organic and inorganic mixtures including, chitosan, alginate, graphene oxide, and gelatin. The chemical, physical, and mechanical properties of these nanocomposites are experimentally evaluated. Silicate-based nanocomposite hydrogels offer unique rheological characteristics, which facilitate the injection process while preserving the mechanical integrity of the construct following extrusion. The injectability of these nanocomposites was assessed by evaluating their shear-thinning properties through multiple rheological analyses. As per the definition of shear-thinning, the viscosity of nanocomposites is directly affected by the applied shear stress; the viscosity of these compositions decreases under shear stress and reverts to the original viscosity after removal of the force. Accordingly, nanocomposite hydrogels with shear-thinning properties can be utilized for extrusion-based 3D printing and for depositing drugs in localized tissue without the jeopardy of being washed away by circulating blood. In addition, the large number of surface interactions and cationic exchange capacity of Laponite nanoparticles improve electrostatic interactions between the nanocomposite components and a wide range of ionic compounds. Accordingly, these chemical properties facilitate the incorporation of stimuli-responsive materials into the polymeric structure of the nanocomposite, allowing for the utilization of these hydrogels in on-demand drug delivery applications. These properties of the silicate-based nanocomposite hydrogels are investigated through swelling and release studies, Fourier transforms infrared spectroscopy (FTIR), and zeta potential measurements. The results of these experiments indicate that the non-covalent electrostatic interactions and chemical properties of these hydrogels improve the solubility and loading efficiency of therapeutic agents. Silicate-based nanocomposite hydrogels may also be utilized for developing electrical conductive bioinks for extrusion-based three-dimensional (3D) printing. Adjusting the viscosity and shear-thinning properties of the hydrogel plays a significant role in the printability of a bioink. For instance, a highly viscous bioink disrupts extrusion, while a bioink with a low viscosity results in the formation of droplets instead of the desired cylindrical filaments. Optimized formulations of the nanocomposite hydrogels are investigated by conducting various mechanical property measurements. Consequently, the unique chemical and rheological properties of the proposed hydrogels make them superior candidates for drug delivery and tissue engineering applications. / Graduate / 2022-03-30

No description available.

Gels are colloidal states of matter in which a solid matrix is dispersed in a liquid phase. Supramolecular gels are formed due to the self-assembly of small gelator molecules in a suitable solvent as a result of specific weak non-covalent interactions between the gelators. The last several decades have witnessed an upsurge in research activities in the area of supramolecular gels not only for academic interests but also for applications in material science. Gels have been investigated as potential avenues for drug delivery and oil recovery applications. Despite their huge potential, the properties of gels are discovered through trial-and-error approaches, which makes control of properties a challenging task. The control becomes extremely hard in a multicomponent gel system, which is a common model for applications in material science. The aim of this thesis is to design a pathway to gain a fundamental understanding on how multiple components in the gel contribute to new properties. This pathway is an attempt to move away from trial-and-error approaches for the development of gels and allows us to make correlations between structure, dynamics and function. The studies reported in this thesis were performed on a two-component gel system comprising a gelator and an additive. The gelator, sodium deoxycholate (NaDC), is a bile salt known for its ability to form a supramolecular gel within a certain pH range. NaDC gels are made up of aggregates distributed between the aqueous phase and the gel structure. NaDC gels are reversible and considered as promising candidates from a functional point of view. The additive, cucurbit[6]uril (CB[6]), is a macrocycle and is known to affect the mechanical properties of NaDC gels at the macroscopic level. In the first project, I studied the effect of CB[6] on the NaDC gel at the microscopic level using dynamic light scattering and fluorescence microscopy experiments. These techniques were used to determine the effect of CB[6] on the gel’s morphology, size of NaDC aggregates, thermo-reversible properties of NaDC gels and the kinetics of NaDC gel formation. My results showed that the effect of CB[6] on NaDC aggregates begins in solutions and is translated to sols and gels. Thermo-reversibility and kinetic studies showed that the effect of CB[6] on NaDC gels goes beyond changes to the gel’s structure and CB[6] was also shown to affect both the gel-sol transition temperatures and time of the gel formation. In the second project, I studied how the release of dyes of different hydrophobicities from NaDC gels was affected by the addition of CB[6]. The release of the dyes pyrene and rhodamine 6G was investigated using a static diffusion method, which was referred to as the top layer method. My results showed that CB[6] has a different effect on the release kinetics of a hydrophilic dye compared to the release of a hydrophobic dye. The observed difference in the release kinetics was attributed to differences in the localization of the dyes in NaDC gels and the role of CB[6] in affecting the distribution of dyes in different regions in the gel. In the third project, I studied the colocalization of a hydrophobic and a hydrophilic dye in NaDC-CB[6] gels with the goal to confirm my hypothesis from the release studies. Dynamics of diffusion of dyes within NaDC-CB[6] gels was investigated using the fluorescence recovery after photobleaching (FRAP) technique. Results from colocalization experiments showed that the addition of CB[6] changes the distribution of hydrophilic dye in the gel. Through colocalization experiments, I was able to showcase the active role of CB[6] in incorporating aggregates from the aqueous phase into the gel structure. Results from FRAP studies showed that, in the presence of CB[6], recovery after bleaching of a hydrophobic dye in the gel structure is slower compared to the dye in the NaDC gel structure. / Graduate

Corrosion related deterioration of aging aircraft has proven to cause reduced flight availability, service lifetime, costly repairs, and if undetected, can result in potentially unsafe operating conditions. The purpose of this research is to develop, fabricate and test optical fiber-based chemical sensors for monitoring corrosion from early stages through the entire corrosion event. Although there are several preventative methods under development to address the problem of corrosion degradation, new techniques are still needed that are cost-effective and reliable to ensure an acceptable health status determination of aging aircraft and civil infrastructure. In using optical fiber-based sensors to detect corrosion precursors such as moisture, pH, nitrates, sulfates, chlorates and corrosion related metal-ion by-products the severity of the corrosive environment can be determined allowing predictive health evaluation of the infrastructure. The long period grating (LPG) element is highly sensitive to refractive index changes and with appropriate design geometry a variety of target molecules can be detected. Optical fiber long period gratings are designed to act as spectral loss elements that couple a discrete wavelength out of the optical fiber as a function of the surrounding refractive index. By applying special coating that change refractive index with absorption of target molecules to the LPG surface, it becomes a transducer for chemical measurement. Presented in this research is the incorporation of pH-sensitive hydrogels with long period gratings for the development of a fiber optic-based pH sensor. Optical fiber-based pH sensors offer numerous advantages in wastewater monitoring, blood diagnostics, bioremediation, as well as chemical and food processing. Specifically this research focuses on pH sensors that can be multiplexed with other chemical sensors for a complete chemical analysis of the corrosive environment. / Master of Science

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Stiffening and softening of extracellular matrix (ECM) are critical processes governing many aspects of biological processes. The most common practice used to investigate these processes is seeding cells on two-dimensional (2D) surfaces of varying stiffness. In recent years, cell-laden three-dimensional (3D) scaffolds with controllable properties are also increasingly used. However, current 2D and 3D culture platforms do not permit spatiotemporal controls over material properties that could influence tissue processes. To address this issue, four-dimensional (4D) hydrogels (i.e., 3D materials permitting time-dependent control of matrix properties) are proposed to recapitulate dynamic changes of ECM properties. The goal of this thesis was to exploit orthogonal enzymatic reactions for on-demand stiffening and/or softening of cell-laden hydrogels. The first objective was to establish cytocompatible hydrogels permitting enzymatic crosslinking and stiffening using enzymes with orthogonal reactivity. Sortase A (SrtA) and mushroom tyrosinase (MT) were used sequentially to achieve initial gelation and on-demand stiffening. In addition, hydrogels permitting reversible stiffening through SrtA-mediated peptide ligation were established. Specifically, poly(ethylene glycol) (PEG)-peptide hydrogels were fabricated with peptide linkers containing pendent SrtA substrates. The hydrogels were stiffened through incubation with SrtA, whereas gel softening was achieved subsequently via addition of SrtA and soluble glycine substrate. The second objective was to investigate the role of dynamic matrix stiffening on pancreatic cancer cell survival, spheroid formation, and drug responsiveness. The crosslinking of PEG-peptide hydrogels was dynamically tuned to evaluate the effect of matrix stiffness on cell viability and function. Specifically, dynamic matrix stiffening inhibited cell proliferation and spheroid formation, while softening the cell-laden hydrogels led to significant increase in spheroid sizes. Matrix stiffness also altered the expression of chemoresistance markers and responsiveness of cancer cells to gemcitabine treatment. markers and responsiveness of cancer cells to gemcitabine treatment.

This diploma thesis is focused on biocompatible polymers degradation study. Copolymers were studied based on poly(lactic-co-glycolic) acid and poly(ethylene glycol) PLGA-PEG-PLGA and further these copolymers modified with itaconic acid ITA-PLGA-PEG-PLGA-ITA. This paper investigated the influence of pH phosphate solution on the degradation of polymers. Degradation of polymers occurred at 37 °C in phosphate solution with pH 4.2, 7.4 and 9.2. High performance liquid chromatography with UV-VIS detection of diode-array type was used for quantitative determination of lactic acid and glycolic acid as the final degradation products. For qualitative identification of additional degradation products were used tandem connection liquid chromatography and mass spectrometry. Gel permeation chromatography with refractive index detector was used to determine the molecular weight decrease polymer chain after the degradation.

No description available.

A polyelectrolyte complex is formed by mixing two oppositely charged polyelectrolytes in a solution. The electrostatic interactions between partially charged polymeric chains lead to the formation of a stable complex while avoiding the use of covalent cross linkers. Since complex formation can improve the stability of polyelectrolyte and metal ions in polyelectrolyte can provide various functionalities, PECs incorporated with metal ions are promising candidates for manufacturing stable and multifunctional structures. While the coordination of metal ions and polyelectrolytes has been extensively investigated in solutions and multilayer films, to our knowledge, no research has been performed to study the effect of metal ion/polyelectrolyte interactions on PECs structures and properties. The following research demonstrates the impact of different metal ions in controlling PEC structure morphology and applications. These discoveries indicate great potential of metal ions in PECs to fabricate functional PEC nanostructures. The research investigates the effect of the interactions between different metal ions and polyelectrolytes on the morphology and properties of PECs, explore the fabrication of different structures using embedded metal ions and understand the impact of metal ion/polyelectrolyte interactions on the nanoparticle structures. The research concludes: 1) incorporating metal ions of different valence into PECs introduces metal ion/polyelectrolyte interactions that can tune the morphology of PECs; 2) metal ion/polyelectrolyte interactions can be used to control the PECs swelling properties and stability in aqueous solutions; 3) the release of embedded metal ions from PECs to aqueous solutions is affected by metal ion/polyelectrolyte interactions; and 4) the embedded metal ions function as a reagent reservoir for various applications to produce functional structures.