1,721,111 research outputs found
Bio-Synthetic Hybrid Materials and Bionanoparticles: A Biological Chemical Approach Towards Material Science
No full textThere is much interest in using biological structures for the fabrication of new functional materials. Recent developments in the particle character and behaviour of proteins and viral particles have had a major impact on the development of novel nanoparticle systems with new functions and possibilities. Bio-Synthetic Hybrid Materials and Bionanoparticles approaches the subject by covering the basics of disciplines involved as well as recent advances in new materials. The first section of the book focusses on the design and synthesis of different bionanoparticles and hybrid structures including the use of genetic modification as well as by organic synthesis. The second section of the book looks at the self-assembling behaviour of bionanoparticles to form new materials. The final section looks at bionanoparticle-based functional systems and materials including chapters on biomedical applications and electronic systems and devices. Edited by leading scientists in bionanoparticles, the book is a collaboration between scientists with different backgrounds and perspectives which will initiate the next generation of bio-based structures, materials and devices
Quaternary ammonium-functionalized carbon nanotubes/alginate nanocomposite hydrogels support myoblast growth and differentiation
Full text linkCarbon nanotube (CNT) composite hydrogels are promising materials for tissue engineering due to the biocompatibility of the matrix and the electrical conductivity of the filler, which is crucial for promoting the growth and functions in electroactive tissues. While pristine CNTs are insoluble, we synthesized and fully characterized a water-soluble CNT derivative (fCNT) bearing quaternary ammonium groups, and we homogeneously dispersed it within alginate-based hydrogels. Through external and internal gelation we obtained two plain and two fCNT-filled hydrogels (HG1 and HG2 and HG1-fCNT and HG2-fCNT, respectively), and we compared the physical properties of the four different materials. A measurement setup and an approach were specifically designed for the electrical characterization of our hydrogel samples, showing that the addition of a low amount (0.1 mg mL−1) of fCNT enhanced the conductivity of the hydrogel from internal gelation (HG2-fCNT) by more than one order of magnitude, from 5.7 × 10−10 to 2.8 × 10−8 S cm−1. Even more interestingly, HG2-fCNT featured a faster transmission of low frequency signals (with time scales from 1 ms to 100 ms, typical of electroactive biological tissues) than the other samples. Finally, the behavior of the four hydrogels as scaffolds for muscle tissue engineering was compared through studies of myoblast viability, proliferation, and differentiation. A relevant improvement in differentiation (more than doubling the number and area of myotubes and the fusion index) was obtained by adding the fCNT in the case of HG2-fCNT, in line of its superior electrical properties. These outcomes hint at the feasibility of using the fCNT combined with the alginate hydrogel in order to support the myoblast growth and proliferation
Site-selective modification of aminoglycoside antibiotics for therapeutic and diagnostic applications
Full text linkAminoglycosides are a potent class of broad-spectrum bactericidal antibiotics and promising starting building blocks for the development of new leads. However, their further use requires a better understanding of the drug modes of action and their derivatives and getting more insights into mechanisms of bacterial resistance. In Chapter 1, the structures, mode of action, and currently known mechanisms of bacterial resistance to aminoglycosides and some of the most potent strategies to overcome bacterial resistance are described. Chapter 2 describes the design and chemical modification of the aminoglycoside neomycin B to improve its antimicrobial function against resistant bacteria. Moreover, we crystalized and resolved the structure of the previously unknown AAC(3)IIIa enzyme, in complex with its natural substrates and the newly developed, most potent derivative. We proposed the mechanism of enzymatic modification catalyzed by the enzyme in the presence of the substrate neomycin B and showed that the newly developed derivative binds to the enzyme in a changed configuration. In Chapter 3, we aimed to achieve spatial and temporal control over aminoglycoside activity by transforming the drug to a temporarily inactivated derivative, which can be re-activated by light. In Chapter 4, we synthesised a library of fluorescently labelled aminoglycosides and investigated their photophysical properties, structure related function, activity and the uptake in E. coli. In Chapter 5, we applied developed fluorescent aminoglycosides conjugates as probes for imaging of Gram-negative bacteria in vitro and in vivo in mouse models rendering the developed fluorescent aminoglycoside conjugates very promising tracers for in-situ diagnostics of infections induced by Gram-negative bacteria
Nanogel: a versatile bioactive drug delivery system
Full text linkDrug delivery system (DDS) is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect inside the human body. Nanogels, a nano-sized hydrogel-like polymeric material, has gained increasing attention for their application as drug delivery carriers due to their excellent colloidal stability in water, tunable chemical and physical structures, good mechanical properties, high loading capability, and good biocompatibility. This thesis developed a versatile drug delivery system based on nanogels. In Chapter I, a brief introduction on drug delivery systems is given and the features of nanogels as DDS are discussed. Chapter II discusses the synthesis and properties of nanogels, the current state-of-art in the field of nanogels in terms of efficiency and applicability for combating infections in the biomedical field are addressed. In Chapter III, a multimodal nanogel was developed to selectively allow molecular conjugated species to either be released inside the cell or remain connected to the polymer network selected by the intracellular environment. Chapter IV describes the development of a hydrophobic antimicrobial agent loaded nanogel for combating planktonic bacteria. Chapter V provides a stable hierarchical nanogel–GelMA composite hydrogel system by covalently embedding nanogels inside the network of GelMA hydrogel. Although this thesis has probed different application potentials of nanogels, there is still some work to do to bring nanogel to the clinical application. The limitation that holds back the process will be discussed in Chapter VI
Macrophage-matrix interactions: orchestrating the fibrotic response?
Full text linkEven though years of research have advanced our understanding of idiopathic pulmonary fibrosis (IPF), the expanded knowledge on risk factors and mechanisms has not yet resulted in effective treatments to control or cure this disease. In patients with IPF, an aberrant wound healing response results in an extracellular matrix (ECM) with altered biochemical and biophysical properties. As key regulators of the wound healing response, macrophages should be able to prevent or resolve fibrosis by regulating the production and degradation of ECM proteins. However, the impact of direct interactions between (fibrotic) matrix and macrophages on the macrophages’ ability to orchestrate the wound healing response is still unclear, and therefore the focus of this thesis. A collagen type I-based in vitro model was developed to study the response of alveolar-like macrophages to collagen layers with varying morphology and stiffness. Macrophages were found to change their shape, behavior, and marker expression depending on the morphology of the collagen they were cultured on. To connect the in vitro effect of different collagen morphologies with the in vivo situation, the amount of structurally disrupted collagen was visualized in lung tissue from patients with IPF and controls. Higher levels of structurally disrupted collagen were found in patients with IPF, indicating that extensive collagen remodeling is taking place. Furthermore, to improve our understanding of macrophage polarization, an optical tweezers-based system was used to study macrophage activation upon a single biochemical stimulus on a single-cell level with very high spatiotemporal resolution. In conclusion, it is without doubt that macrophages are able to sense changes in their microenvironment and subsequently change their phenotype. However, a better understanding of fibrosis-related ECM changes and functional macrophage polarization is required to clarify the exact role of macrophage-matrix interactions in orchestrating the fibrotic response
Pre-clinical Development of Nanoparticles and Nanogels for Drug and Gene Delivery to Glioblastoma
Full text linkDespite extensive surgical resection and adjuvant therapy, the median survival of Glioblastoma multiforme (GBM) patients is only about 12-18 months. Also, many patients are not recommended for surgery due to an inoperable location of the tumor or poor physical performance of the patient. Therefore, on the one hand, it is necessary and promising to study and screen more drugs for adjuvant treatment of GBM. On the other hand, the problem of therapeutic agents, e.g., short circulating half-life, difficulty in accumulating in tumor area, controlling drug release, and overcoming the barriers of GBM need to be solved. In Chapter 2 of this thesis, curcumin-loaded zein nanoparticles that were functionalized with the ganglioside GM1-binding G23 peptide efficiently traversed an in vitro BBB model, stimulated 3D tumor spheroid penetration, inhibited glioblastoma cell growth and exhibited the ability to circulate in the blood. Whether curcumin-loaded nanoparticles (CUR-NPs) can sensitize human glioblastoma U87 cells and GBM patient-derived neurospheres to the chemotherapeutic temozolomide TMZ treatment, administered either as free TMZ or as TMZ-cyclodextrin (TMZ@CD) inclusion complexes was investigated in Chapter 3. CUR-NPs enhanced the inhibitory effects of TMZ and TMZ@CD on the proliferation of U87 cells, GG16 and GSC23 neurospheres. In Chapter 4, we evaluated the ability of the tertiary amine-, quaternized ammonium-, and aliphatic quaternized ammonium-functionalized p(NIPAM) nanogels (i.e., NGs, NGs-MI, and NGs-BDD, respectively) to mediate gene transfection. NGs-BDD/pDNA complexes show a notable gene transfer efficiency, which can be ascribed to their ability to facilitate endosomal escape by perturbing the endosomal/lysosomal membrane
Exploring combined influences of material topography, stiffness and chemistry on cell behavior at biointerfaces
Full text linkComplexe materiaalgrensvlakken zijn ontworpen voor het exploreren van cel-materiaal interactions om de relatie tussen biomateriaal eigenschappen en biologische prestatie blood te leggen welke in de toekomst gebruikt kan worden voor geadvanceerde weefselbouw en regeneratieve geneeskunde. Cellen nemen altijd verscheidene signalen op uit hun microomgeving en hierdoor moeten we vele verschillende parameters van de biomaterialen incorporeren zodat we deze gedragingen zo accuraat mogelijk kunnen bestuderen en de toestand van de cel koppelen aan de interactie die wordt aangegaan met de materiaal eigenschappen. Om controle te verkrijgen over cel gedrag en deze te kunnen sturen, is het cruciaal om optimaal celgedrag te bepalen waarbij in detail naar een groot aantal parameterwaardes wordt gekeken binnen een groot spreidingsgebied. Naar verwachting illusteren de bevindingen beschreven in dit proefschrift andere onderzoekers dat celgedrag in een complexere mix van stimuli moet worden bestudeerd. Ons werk zoals hier beschreven gaat niet alleen om het verkrijgen van meer kennis op het gebied van celgedrag omder invloed van materiaaleigenschappen maar ook om het toe te passen als manier om hoogwaardige biomaterialen te ontwikkelen voor commerciele doeleinden
The effect of wettability and stiffness on stem cell behavior at bioinerfaces
Full text linkThis thesis shows new approaches to influence known materials to identify optimal physical parameters and parameter combinations at biointerfaces and how these affect early cellular behavior. It is important to carefully test the parameters of the biointerface towards cell response in a systematic way in order to yield strong conclusions from it. Therefore, the generation of systems which allow this kind of testing is the main achievement of this thesis. Here, materials frequently used in the clinics are modified using innovative approaches, which hopefully facilitates a shorter route to actual clinical applications. Surface gradient testing devices, which are capable of elucidating effects of wettability, stiffness and their combination are developed and used for the 2D biointerface testing. In order to test efficiently in a 3D environment as well as the possibility to change three parameters in independent directions, first attempts to manipulate stiffness in a 3D system were made. This material is further facilitated as potential wound healing material. At the end, findings and general conclusions are placed in perspective where system drawbacks are still eminent but great strides are expected to be made in the field of biointerfaces as initial findings presented in this thesis have enabled this. The idea of combining and systematically manipulating physical parameters is presented and possibilities for future improvements are displayed
CHAPTER 9. Virus-Based Systems for Functional Materials
No full textVirus-based bionanotechnology holds the promise of control over the structure, properties and functionality of materials at the nanometre scale. After all, viruses, and by extension virus-like particles (VLPs), represent some of the largest hierarchical protein constructs found in Nature. Their symmetrical architecture and their high degree of monodispersity, compared with other nanoparticles, make them unique as nanobuilding blocks. Furthermore, many of these particles seem to have specific and tuneable physical properties that can be utilized for their further function and manipulation. Viruses and VLPs are therefore highly desirable nanobuilding blocks that could find applications ranging from nanocontainers, for studying reactions in confinement or drug delivery, to modular structural components, that allow for the creation of complex nanoarchitectures, and eventually functional materials. This chapter is intended to generate an understanding of how the structure, modification and organization of viruses enable them to be the key component in these potential, functional materials, a field recently introduced as chemical virology. Ultimately, these functional virus-based materials could allow the construction of novel optical, electronic, catalytic, imaging and other nano-scale precision-based applications.</p
Topography-mediated myofiber formation and endothelial cell sprouting
Full text linkDirectional topography is often used in cell alignment. This thesis explores the influences of directional topography and topography-aligned differentiated myoblasts in combination with endothelial cells in triggering capillary network formation for tissue engineering of skeletal muscle. Directional topography gradients were used to study the optimum alignment of differentiated myoblasts i.e., myotubes. It was shown that human myoblasts aligned and differentiated irrespective of the topography section. Subsequently, endothelial cells (ECs) were added to the same directional topographic systems, showing that ECs formed unstable sprouting networks that aggregated on the smaller topographies and flat parts whereas ECs themselves aligned on the larger topographies. In addition, different coatings were investigated, such as gelatin, fibronectin, and instructive adipose tissue-derived stromal cell (ASC). We identified that the ASC coating stabilized newly the formed sprouting networks. In addition, we tested the hypothesis that “topography-driven aligned human myotubes promote and support vascular network formation as a prelude to in vitro engineered vascularized skeletal muscle”. As a result, we showed that pre-aligned myotubes support early network sprouting of microvascular endothelial cells by providing collagen fibers and laminin but require accessory cells such as pericytes to complete the vascularization process in vitro. In conclusion, our results showed that aligned topography has a tremendous impact on myotube development and endothelial cell guidance. Topographical cues can be stronger than chemical cues and need further study and consideration in tissue engineering of skeletal muscle
- …
