Mathias Gressenbuch

Biodegradable and adjustable sol-gel glass based hybrid scaffolds from multi-armed oligomeric building blocks

Biodegradability is a crucial characteristic to improve the clinical potential of sol-gel-derived glass materials. To this end, a set of degradable organic/inorganic class II hybrids from a tetraethoxysilane(TEOS)-derived silica sol and oligovalent cross-linker oligomers containing oligo(d,l-lactide) domains was developed and characterized. A series of 18 oligomers (Mn: 1100-3200Da) with different degrees of ethoxylation and varying length of oligoester units was established and chemical composition was determined. Applicability of an established indirect rapid prototyping method enabled fabrication of a total of 85 different hybrid scaffold formulations from 3-isocyanatopropyltriethoxysilane-functionalized macromers. In vitro degradation was analyzed over 12months and a continuous linear weight loss (0.2-0.5wt%/d) combined with only moderate material swelling was detected which was controlled by oligo(lactide) content and matrix hydrophilicity. Compressive strength (2-30MPa) and compressive modulus (44-716MPa) were determined and total content, oligo(ethylene oxide) content, oligo(lactide) content and molecular weight of the oligomeric cross-linkers as well as material porosity were identified as the main factors determining hybrid mechanics. Cytocompatibility was assessed by cell culture experiments with human adipose tissue-derived stem cells (hASC). Cell migration into the entire scaffold pore network was indicated and continuous proliferation over 14days was found. ALP activity linearly increased over 2weeks indicating osteogenic differentiation. The presented glass-based hybrid concept with precisely adjustable material properties holds promise for regenerative purposes. STATEMENT OF SIGNIFICANCE Adaption of degradation kinetics toward physiological relevance is still an unmet challenge of (bio-)glass engineering. We therefore present a glass-derived hybrid material with adjustable degradation. A flexible design concept based on degradable multi-armed oligomers was combined with an established indirect rapid prototyping method to produce a systematic set of porous sol-gel-derived class II hybrid scaffolds. Mechanical properties in the range of cancellous bone were narrowly controlled by hybrid composition. The oligoester introduction resulted in significantly increased compressive moduli. Cytocompatible hybrids degraded in physiologically relevant time frames and a promising linear and controllable weight loss profile was found. To our knowledge, our degradation study represents the most extensive long-term investigation of sol-gel-derived class II hybrids. Due to the broad adjustability of material properties, our concept offers potential for engineering of biodegradable hybrid materials for versatile applications.

Synthesis and structural chemistry of bicyclic hexaaza-dithia macrocycles containing pendant donor groups

A short and efficient synthesis of a series of macrobicyclic aza-thioethers with pendant allyl (8, 13, 14), cyanethyl (15), 3-aminopropyl (16), 2-methoxyacetyl (17, 19), 2-methoxyethyl (18, 20), and tert-butyloxycarbonyl substituents (22, 23) has been achieved. The parent macrobicycles 1 and 2 are readily alkylated without overalkylation and without affecting the masked thiolate functions. The protocol is also feasible for the synthesis of macrobicycles with different alkyl groups on the benzylic and central nitrogen atoms of the linking diethylene triamine units. The identity of the compounds was substantiated using ESI MS, FT-IR, 1H-NMR, and 13C-NMR spectroscopy. The crystal and molecular structures of six compounds (8, 15, 17·3DMSO, 19·2DMSO·2H2O, 20 and 23) were additionally solved. The macrocycles are rather flexible and can adopt folded or stepped conformations. The ability of the compounds to form inclusion complexes with DMSO is also demonstrated. The crystal structures are governed by extensive inter- and intramolecular CH⋯π interactions.