Chemo-enzymatic synthesis of chiral fluorine-containing building blocks

Contains fulltext : 58912.pdf (publisher's version ) (Open Access)Two complementary strategies for the synthesis of optically active fluorine-containing building blocks have been probed. The first strategy involves either the enzymatic resolution of fluorinated alpha,alpha-disubstituted -alpha-amino acid amides, or the asymmetric hydrogenation of fluorinated clehydroamino acids. The second strategy involves the transition metal-catalyzed introduction of fluorine-containing substituents onto olefin- or acetylene-containing alpha-H-alpha-amino acids. These amino acids in turn are made optically active by enzymatic resolution of the corresponding amides

Fluorous chemistry applications in synthesis and catalysis

Contains fulltext : 83518.pdf (Publisher’s version ) (Open Access)Radboud Universiteit Nijmegen, 13 september 2010Promotor : Rutjes, F.P.J.T. Co-promotor : Delft, F.L. van156 p

Conjugation of nucleosides and oligonucleotides by [3+2] cycloaddition

Contains fulltext : 72080.pdf (publisher's version ) (Closed access)4 p

Labeling of Collagen Type I Templates with a Naturally Derived Contrast Agent for Noninvasive MR Imaging in Soft Tissue Engineering

Contains fulltext : 195606.pdf (publisher's version ) (Closed access)In vivo monitoring of tissue-engineered constructs is important to assess their integrity, remodeling, and degradation. However, this is challenging when the contrast with neighboring tissues is low, necessitating labeling with contrast agents (CAs), but current CAs have limitations (i.e., toxicity, negative contrast, label instability, and/or inappropriate size). Therefore, a naturally derived hemin-L-lysine (HL) complex is used as a potential CA to label collagen-based templates for magnetic resonance imaging (MRI). Labeling does not change the basic characteristics of the collagen templates. When hybrid templates composed of collagen type I reinforced with degradable polymers are subcutaneously implanted in mice, longitudinal visualization by MRI is possible with good contrast and in correlation with template remodeling. In contrast, unlabeled collagen templates are hardly detectable and the fate of these templates cannot be monitored by MRI. Interestingly, tissue remodeling and vascularization are enhanced within HL-labeled templates. Thus, HL labeling is presented as a promising universal imaging marker to label tissue-engineered implants for MRI, which additionally seems to accelerate tissue regeneration

A theranostic dental pulp capping agent with improved MRI and CT contrast and biological properties

Contains fulltext : 177800.pdf (publisher's version ) (Closed access)Different materials have been used for vital dental pulp treatment. Preferably a pulp capping agent should show appropriate biological performance, excellent handling properties, and a good imaging contrast. These features can be delivered into a single material through the combination of therapeutic and diagnostic agents (i.e. theranostic). Calcium phosphate based composites (CPCs) are potentially ideal candidate for pulp treatment, although poor imaging contrast and poor dentino-inductive properties are limiting their clinical use. In this study, a theranostic dental pulp capping agent was developed. First, imaging properties of the CPC were improved by using a core-shell structured dual contrast agent (csDCA) consisting of superparamagnetic iron oxide (SPIO) and colloidal gold, as MRI and CT contrast agent respectively. Second, biological properties were implemented by using a dentinogenic factor (i.e. bone morphogenetic protein 2, BMP-2). The obtained CPC/csDCA/BMP-2 composite was tested in vivo, as direct pulp capping agent, in a male Habsi goat incisor model. Our outcomes showed no relevant alteration of the handling and mechanical properties (e.g. setting time, injectability, and compressive strength) by the incorporation of csDCA particles. In vivo results proved MRI contrast enhancement up to 7weeks. Incisors treated with BMP-2 showed improved tertiary dentin deposition as well as faster cement degradation as measured by microCT assessment. In conclusion, the presented theranostic agent matches the imaging and regenerative requirements for pulp capping applications. STATEMENT OF SIGNIFICANCE: In this study, we combined diagnostic and therapeutic agents in order to developed a theranostic pulp capping agent with enhanced MRI and CT contrast and improved dentin regeneration ability. In our study we cover all the steps from material preparation, mechanical and in vitro characterization, to in vivo study in a goat dental model. To the best of our knowledge, this is the first time that a theranostic pulp capping material have been developed and tested in an in vivo animal model. Our promising results in term of imaging contrast enhancement and of induction of new dentin formation, open a new scenario in the development of innovative dental materials