Biomaterials are widely used in medical practice to help maintain, improve or restore diseased tissues or organs. The successful integration of biomaterials with host tissue depends on substratum surface properties, as well as host tissue quality and its regulatory environment. The overall goal of this dissertation is to incorporate these three factors to achieve better biomaterial-host tissue interactions. Important surface properties include surface topography, surface energy, chemical composition and surface charge. We designed a new titanium (Ti) substratum with modified surface chemical composition by preventing the contamination when in contact with the atmosphere. The new Ti surface has lower carbon contamination and promotes osteoblast differentiation phenotype. The osteogenic effect is synergistic with micrometer and sub-micrometer scale surface structures. To further investigate the effects of bone quality on peri-implant bone formation, we developed a novel mouse femoral medullary bone formation model. This new model will facilitate research evaluating the effects of biomaterial surface treatments in host animals with deficient bone development, including genetically engineered mice. Finally, we studied sexual dimorphism in the response of osteoblasts to systemic regulatory hormones 1¦Á,25-dihydroxyvitamin D3 and 17¦Â-estradiol. The results showed intrinsic differences in male and female osteoblasts with respect to their differentiation and their responses to hormones, suggesting that host chromosomal sex should be considered in biomaterial research. Taken together, this research provides fundamental information on biomaterial surface properties and the regulation of host tissue response, which are important in guiding biomaterial design and evaluation.

Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009. / Committee Chair: Dr. Uwe H.F. Bunz; Committee Member: Dr. Andrew Lyon; Committee Member: Dr. Laren Tolbert; Committee Member: Dr. Nicholas Hud; Committee Member: Dr. Sherry Michele Owen. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Studies have shown that tumor cells are susceptible to pharmacological targeting of their altered glycolytic metabolism with a variety of compounds that result in apoptosis. One such compound, 3-bromopyruvate (3-BP), has been shown to eradicate cancer in an animal model. However, no studies have shown whether the apoptotic fragments resulting from 3-BP treatment have the capacity to elicit an immunogenic cell death that activates dendritic cells, the primary antigen presenting cell in the immune system. Immunogenic cell death is critical to eliciting an effective adaptive immune response that selectively kills additional target cells and generates immunological memory. We demonstrated that 3-bromopyruvate induced apoptosis in a number of different murine breast cancer cell lines, including the highly metastatic 4T1 line. The dying tumor cells stimulated immature dendritic cells (DCs) of the immortal JAWS II cell line to produce high levels of the pro-inflammatory cytokine IL-12, and increased their expression of key co-stimulatory molecules CD80 and CD86. The activated dendritic cells showed increased uptake of fragments from dying tumor cells that correlated with the increased levels of calreticulin on the surface and release of high group motility box 1 (HMGB1) of the latter following 3-BP treatment. Additionally, the anti-phagocytic signal CD47 present on breast cancer cells was reduced by treatment with 3-bromopyruvate when compared to the levels on untreated 4T1 cells. 3-BP treated breast cancer cells were able to activate dendritic cells through TLR4 signaling. Signaling was dependent on both the expression of surface calreticulin and on the extracellular release of high mobility group box 1 protein (HMGB1) during the process of immunogenic cell death. Killing by 3-BP was compared to mitoxantrone and doxorubicin, among the few chemotherapeutics that induce immunogenic cell death. 3-BP killing was likewise compared to camptothecin, a compound that fails to induce immunogenic cell death. Importantly, 3-BP did not markedly decrease the levels of the key peptide presenting molecule MHC I on DCs that were co-cultivated with dying tumor cells. Treatment of the highly aggressive triple negative BT-20 human breast cancer cell line with 3-BP also induced an immunogenic cell death, activating human dendritic cells in vitro. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2017. / FAU Electronic Theses and Dissertations Collection

The miniaturization of electronics is a technique that holds a lot of potential in improving system performance in a variety of applications. The simultaneous miniaturization of sensors into the nano-scale has provided new ways to probe biological systems. Careful co-design of these electronics and sensors can unlock measurements and experiments that would otherwise be impossible to achieve. This thesis describes the design of two such instrumentation amplifiers and shows that significant gains in temporal resolution and noise performance are possible through careful optimization. A custom integrated amplifier is developed for improving the temporal resolution in nanopore recordings. The amplifier is designed in a commercial 0.18 μm complementary metal-oxide-semiconductor (CMOS) process. A platform is then built with the amplifier at its core that integrates glass-passivated solid-state nanopores to achieve measurement bandwidth over an order of magnitude greater than the state of the art. The use of wavelet transforms for denoising the data and further improving the signal-to-noise ratio (SNR) is then explored. A second amplifier is designed in a 0.18 μm CMOS process for intracellular recordings from neurons. The amplifier contains all the compensation circuitry required for canceling the effects of the electrode non-idealities. Compared to equivalent commercial systems and the state of the art, the amplifier performs comparably or better while consuming orders of magnitude lower power. These systems can inform the design of extremely miniaturized application-specific integrated amplifiers of the future.

Cell adhesion to extracellular matrix proteins is critical to physiological and pathological processes as well as biomedical and biotechnological applications. Cell adhesion is a highly regulated process involving initial receptor-ligand binding, and subsequent clustering of these receptors and rapid association with the actin cytoskeleton as focal adhesions are assembled. Focal adhesions enhance adhesion, functioning as structural links between the cytoskeleton and the extracellular matrix and triggering signaling pathways that direct cell function. The objective of this thesis research is to develop a mechanical and biochemical analysis of the adhesion strengthening response. Our central hypothesis was that focal adhesion size and position regulate cell adhesion strength by controlling the distribution of mechanical loading. We engineered micropatterned surfaces to control the size and position of focal adhesions in order to analyze the contributions of these specialized adhesive structures to adhesion strengthening. By applying surface micropatterning techniques, we showed robust control over cell-substrate contact area and focal adhesion assembly. Using a hydrodynamic shear assay to quantify adhesion strength to micropatterned substrates, we observed significant adhesive area- and time-dependent increases in adhesion strength. Complimentary biochemical assays allowed us to probe the role of structural proteins recruited to focal adhesions and examine the structure-function relationships between these adhesive structures and adhesion strength. These findings provide insights into the role of focal adhesions in adhesion strengthening, and may contribute to tissue engineering and biomaterials applications.

The synthesis and biological sensing applications of novel water soluble poly(para-phenyleneethynylene)s (PPEs) are presented. The ease of synthesis, synthetic variability, and dramatic chromicity of PPEs makes them well suited for biological and sensing applications. Molecular recognition and signal transduction can be achieved by using PPEs as sensory materials. By incorporating biological functional groups (e.g. sugars), PPEs can efficiently detect the presence of toxic heavy metals, proteins, and bacteria through either fluorescence quenching or enhancement. Rapid, precise, and convenient sensory arrays for the detection of biological analytes are possible through the formation of gold nanoparticle-PPE constructs.

Thesis (Ph.D.)--Flinders University, School of Chemistry, Physics and Earth Sciences. / Typescript bound. Includes bibliographical references and list of publications. Also available online.

The adsorption of biologically active molecules, such as the DNA bases, amino acids, on solid surfaces has been the subject of a number of experimental and theoretical studies in the past years. The understanding of the self-assembly mechanism of bioactive molecules on surfaces not only is fundamentally important in the preparation of bioactive surfaces, but also provides us insight into the origins of life and homo-chirality in nature. In this thesis, the adsorption behaviour of adenine and phenylglycine molecules on the Cu(110) surface has been investigated in order to understand the effect of experimental parameters like coverage, annealing temperature etc. on the molecular orientation and the ordering of the adlayer structures. The thesis is organised in six parts: Chapter I gives an introduction to the relevance of surface sciences studies, describing the phenomena of surface chirality and molecular adsorption behaviours on surfaces. Chapter II gives an overview of the experimental techniques and introduces basic concepts of theoretical calculation. Chapter III investigates the effect of experimental parameters, e.g. surface coverage, annealing temperature and substrate temperature on molecular diffusion, molecular orientation and ordering of the adlayer structures. LT-STM examination of the contrast variations of adenine chains and isolated adsorbate as a function of the tip-sample bias voltage is also presented with the aim to understand the tunnelling mechanism. Chapter IV shows RAIR spectra studies of the evolution of phenylglycine molecular orientation as a function of surface coverage at room temperature. The adsorption geometry and binding nature of phenylglycine is discussed. Chapter V concerns with the adsorption behaviours of phenylglycine and adenine on Cu(110) surface pre-covered with oxygen. Chapter VI summarises the conclusions and describes the outlook of some future work.

Indiana University-Purdue University Indianapolis (IUPUI) / It is increasingly recognized that mechanical properties of substrates play a pivotal role in the regulation of cellular fate and function. However, the underlying mechanisms of cellular mechanosensing still remain a topic of open debate. Traditionally, advancements in this field have been made using polymeric substrates of adjustable stiffness with immobilized linkers. While such substrates are well suited to examine cell adhesion and migration in an extracellular matrix environment, they are limited in their ability to replicate the rich dynamics found at cell-cell interfaces. To address this challenge, we recently introduced a linker-functionalized polymer-tethered multi-bilayer stack, in which substrate stiffness can be altered by the degree of bilayer stacking, thus allowing the analysis of cellular mechanosensitivity. Here, we apply this novel biomembrane-mimicking cell substrate design to explore the mechanosensitivity of C2C12 myoblasts in the presence of cell-cell-mimicking N-cadherin linkers. Experiments are presented, which demonstrate a relationship between the degree of bilayer stacking and mechanoresponse of plated cells, such as morphology, cytoskeletal organization, cellular traction forces, and migration speed. Furthermore, we illustrate the dynamic assembly of bilayer-bound N-cadherin linkers underneath cellular adherens junctions. In addition, properties of individual and clustered N-cadherins are examined in the polymer-tethered bilayer system in the absence of plated cells. Alternatively, substrate stiffness can be adjusted by the concentration of lipopolymers in a single polymer-tethered lipid bilayer. On the basis of this alternative cell substrate concept, we also discuss recent results on a linker-functionalized single polymer-tethered bilayer substrate with a lateral gradient in lipopolymer concentration (substrate viscoelasticity). Specifically, we show that the lipopolymer gradient has a notable impact on spreading, cytoskeletal organization, and motility of 3T3 fibroblasts. Two cases are discussed: 1. polymer-tethered bilayers with a sharp boundary between low and high lipopolymer concentration regions and 2. polymer-tethered bilayers with a gradual gradient in lipopolymer concentration.