Phospholipid vesicles are biocompatible, and have potential for intracellular applications, but minimal membrane integrity limits their use in membrane-rich environments. Stabilized membranes overcome this limitation while maintaining biocompatible surface structures. Additionally, the modularity of phospholipid bilayer makes them ideal components when designing biologically inspired sensors. Membrane composition can be tailored to specific applications, transmembrane proteins can provide added functionalities, and the isolated interior can prevent cytotoxic and interfering detection chemistries from altering the cellular environment. This work has focused on expanding the capabilities of stabilized phospholipid membranes, and determining which formulations hold promise in developing stabilized phospholipid vesicle nanosensors.Current membrane stabilization methods suffer from either incomplete stabilization, or irreversible stabilization limiting the applications of vesicle nanosensors. Therefore, a facile method to prepare robust phospholipid vesicles using commonly available phospholipids stabilized via the formation of an interpenetrating, acid-labile, cross-linked polymer network that imparts controlled polymer destabilization and subsequent vesicle degradation was developed. Upon exposure to acidic conditions, the highly cross-linked polymer network was converted to linear polymers, substantially reducing vesicle stability upon exposure to chemical and physical insults. The resultant transiently stabilized vesicles have potential for enhanced drug delivery and chemical sensing applications requiring minimal membrane defects, and allow for improved physiological clearance.Some vesicle nanosensor schemes may require the passive diffusion of low molecular weight species across the membrane in addition to controllable degradation. Therefore, the acid-degradable, polymer-stabilized, phospholipid vesicle production method was extended to bis-SorbPC membranes by simultaneously polymerizing the vesicle with an acetal-containing cross-linker. The vesicles display prolonged stability under physiological conditions, and significant additional stability compared to vesicles composed of naturally occurring phospholipids. The vesicles demonstrated potential utility for sensing and therapeutic applications.Phospholipid vesicles can also serve as labels to observe movement in macromolecular biological assemblies, but a dearth of caged fluorescent labels limits design and function. Therefore, the first caged fluorescent thiol was synthesized, shown to label amines rapidly, and demonstrated the required photolytic properties. The caged fluorescent thiol has potential as a label in observing the movement of macromolecular biological assemblies and as a fluorescent probe for observing endosomal trafficking and release.

The impact of lactate producing direct-fed microbial (DFM) on growth performance and rumen fermentation in beef cattle was explored in four studies. Experiment 1 studied the interaction between DFM and degradable intake protein (DIP) supply in receiving cattle. No differences (P≥0.06) in intake, morbidity, or immune response were observed; however, during the first 28 d gain and efficiency responses to DFM were dependent on DIP (DIP×DFM P≤0.05). Experiment 2 showed that in vitro gas production and select endpoint metabolites differed (P≤0.04) with DFM application. Experiment 3 compared lactate producing DFM to a lactate producing/utilizing DFM in finishing cattle. No differences (P≥0.14) in intake, gain, efficiency, or carcass characteristics were observed between control and lactate DFM; however, gain and growth efficiency differed (P≤0.05) between the lactate producing and lactate producing/utilizing DFM during the later portions of feeding. Experiment 4 studied the impact of DFM on ruminal fermentation, lactate utilization, and total tract digestibility. Ruminal pH and molar proportions of acetate were increased (P≤0.05) with DFM; however, lactate utilization and total tract digestibility did not differ (P≥0.33). The studies suggest that DFM improve growth performance during receiving and responses are at least partly mediated through differences in ruminal fermentation.

A degradable/polar/hydrophobic/ionic (D-PHI) polyurethane with properties intended to promote tissue regeneration in a small diameter peripheral artery vascular graft was evaluated for cell biocompatibility and growth. Films were cast in polypropylene 96 well plates for monocyte/endothelial cell (EC) co-culture in vitro studies and porous scaffold discs were implanted in an in vivo subcutaneous mouse model. After 7 days in culture the co-culture demonstrated cell adhesion and growth, low esterase activity (a measure of degradative potential and cell activation), no detectable release of pro-inflammatory cytokine (tumour necrosis factor -α) but measurable anti-inflammatory interleukin (IL)-10. The EC and the co-culture expressed the EC biomarker CD31, whereas the monocyte monoculture did not. Cytokine array analysis of the in vivo characterization of D-PH supported an anti-inflammatory phenotype of cells at the site of the implant. Levels of IL-6 significantly decreased over time while IL-10 was significantly higher at 6 weeks post implant. TNF-α levels did not change significantly from 24 hours onwards, however the trend was towards lesser amounts following the initial time point. Histological analysis of the explanted scaffolds showed excellent tissue ingrowth and vascularization. A live/dead stain showed that the cells infiltrating the scaffolds were viable. Both the in vitro and in vivo results of this thesis indicate that D-PHI is a good candidate material for tissue engineering a peripheral artery vascular graft.

A degradable/polar/hydrophobic/ionic (D-PHI) polyurethane with properties intended to promote tissue regeneration in a small diameter peripheral artery vascular graft was evaluated for cell biocompatibility and growth. Films were cast in polypropylene 96 well plates for monocyte/endothelial cell (EC) co-culture in vitro studies and porous scaffold discs were implanted in an in vivo subcutaneous mouse model. After 7 days in culture the co-culture demonstrated cell adhesion and growth, low esterase activity (a measure of degradative potential and cell activation), no detectable release of pro-inflammatory cytokine (tumour necrosis factor -α) but measurable anti-inflammatory interleukin (IL)-10. The EC and the co-culture expressed the EC biomarker CD31, whereas the monocyte monoculture did not. Cytokine array analysis of the in vivo characterization of D-PH supported an anti-inflammatory phenotype of cells at the site of the implant. Levels of IL-6 significantly decreased over time while IL-10 was significantly higher at 6 weeks post implant. TNF-α levels did not change significantly from 24 hours onwards, however the trend was towards lesser amounts following the initial time point. Histological analysis of the explanted scaffolds showed excellent tissue ingrowth and vascularization. A live/dead stain showed that the cells infiltrating the scaffolds were viable. Both the in vitro and in vivo results of this thesis indicate that D-PHI is a good candidate material for tissue engineering a peripheral artery vascular graft.

Se pretende obtener un material semibiodegradable basado en ácido hialurónico químicamente enlazado a cadenas de polímeros acrílicos. Los hidrogeles de ácido hialurónico presentan en general buenas características para su utilización en regeneración del sistema nervioso central: es biodegradable, es un componente importante del tejido neural, sus propiedades mecánicas son semejantes a las del tejido cerebral, promueve la formación de nuevos capilares (angiogénesis), y limita la inflamación. Con este nuevo material se pretende mejorar el excesivo grado de hinchado en medio fisiológico, su rápida degradación, mejorar la adhesión celular, además la matriz permanente de las cadenas acrílicas pueden actuar como un soporte permanente durante el proceso regenerativo sin que se produzca una pérdida brusca de propiedades mecánicas y estructurales. El trabajo consiste en caracterizar este nuevo material así como los productos intermedios necesarios para su obtención final, comparándolo con las propiedades de un hidrogel de ácido hialurónico sin incorporar cadenas acrílicas. Los estudios celulares se llevaran a cabo in vitro, como fase preliminar para futuros implantes en el cortex cerebral, estudiando la capacidad de diferenciación de precursores neurales y de generación de nuevos capilares con el fenotipo típico de la barrera hematoencefálica, mediante el estudio de cocultivos de precursores neurales y células endoteliales. / Perez Garnes, M. (2015). Structures based on semi-degradable biomaterials for neural regeneration in the central nervous system [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/48799 / TESIS

Adhesives are widespread. They hold together the furniture, cars and electronics that we use on a daily basis. The majority of commercially available glues are sourced from petroleum-based monomers and are not degradable in any practical way. The permanent nature of these adhesive materials makes disassembly for recycling difficult. Current bio-based glues such as hide and starch glue are not strong enough to compete with commercial glues. Inspiration from nature is helping us to tackle this problem. Marine mussels achieve strong bonding to underwater surfaces through the use of adhesive plaques containing the uncommon amino acid 3,4-dihydroxyphenylalanine. Incorporating this chemistry into a degradable polylactic acid backbone allows for the development of strong bonding biodegradable glue. Throughout this work, the synthesis of these materials is discussed as well as methods to improve the bonding of these materials to compete with commercial glues. The degradation of these materials as well as their cytocompatibility is discussed.

Quartz Crystal Microbalance (QCM) is a sensitive and effective technique to analyze mass changes at the interface between a solid material and a liquid environment. In this Master thesis, QCM was employed for evaluating the interactions between selected degradable polymers and nanodiamond particles (nDP), fibronectin and the growth factor BMP-2.   Many parameters must be adapted to allow QCM measurements involving degradable polymers. These parameters were then tailored to allow QCM measurements with PLA, poly(LLA-co-CL), poly(TMC-D-LA) and PS.   Moreover, QCM provides quantitative measurements of protein adsorption on degradable polymers. The behavior of PLA and poly(LLA-co-CL) was further evaluated and compared with respect to protein adsorption. This behavior was demonstrated to be different for the two polymers considered and to be dependent on protein concentration in solution.   Eventually, exploiting QCM it was also possible to assess the relationship between nDP and the adsorption of fibronectin and BMP-2 onto PLA and poly(LLA-co-CL).

No description available.

No / Functional, degradable polymers were synthesized via the copolymerization of vinyl acetate (VAc) and 2-methylene-1,3-dioxepane (MDO) using a macro-xanthate CTA, poly(N-vinylpyrrolidone), resulting in the formation of amphiphilic block copolymers of poly(NVP)-b-poly(MDO-co-VAc). The behavior of the block copolymers in water was investigated and resulted in the formation of self-assembled nanoparticles containing a hydrophobic core and a hydrophilic corona. The size of the resultant nanoparticles was able to be tuned with variation of the hydrophilic and hydrophobic segments of the core and corona by changing the incorporation of the macro-CTA as well as the monomer composition in the copolymers, as observed by Dynamic Light Scattering, Static Light Scattering, and Transmission Electron Microscopy analyses. The concept was further applied to a VAc derivative monomer, vinyl bromobutanoate, to incorporate further functionalities such as fluorescent dithiomaleimide groups throughout the polymer backbone using azidation and “click” chemistry as postpolymerization tools to create fluorescently labeled nanoparticles. / University of Warwick, BP, The Royal Society

Yes / Here, we report how the stability of polyion complex (PIC) particles containing Pseudomonas aeruginosa’s elastase (LasB) degradable peptides and antimicrobial poly(ethylene imine) is significantly improved by careful design of the peptide component. Three LasB‐degradable peptides are reported herein, all of them carrying the LasB‐degradable sequence −GLA− and for which the number of anionic amino acids and cysteine units per peptide were systematically varied. Our results suggest that while net charge and potential to cross‐link via disulfide bond formation do not have a predictable effect on the ability of LasB to degrade these peptides, a significant effect of these two parameters on particle preparation and stability is observed. A range of techniques has been used to characterize these new materials and demonstrates that increasing the charge and cross‐linking potential of the peptides results in PIC particles with better stability in physiological conditions and upon storage. These results highlight the importance of molecular design for the preparation of PIC particles and should underpin the future development of these materials for responsive drug delivery. / Wellcome Trust, EPSRC, Birminghan Science City, European Regional Development Fund, University of Birmingham