Engineering cell attachments to scaffolds in cartilage tissue engineering

One of the challenges of tissue engineering, a promising cell-based treatment for damaged or diseased cartilage, is designing the scaffold that provides structure while the tissue regenerates. In addition to the scaffold material’s biocompatibility, mechanical properties, and ease of manufacturing, scaffold interactions with the cells must also be considered. In cartilage tissue engineering, a range of scaffolds with various degrees of cell attachment have been proposed, but the attachment density and type have yet to be optimized. Several techniques have been developed to modulate cell adhesion to the scaffold. These studies suggest that the need for cell attachment in cartilage tissue engineering may vary with cell type, stage of differentiation, culture condition, and scaffold material. Further studies will elucidate the role of cell attachment in cartilage regeneration and enhance efforts to engineer cell-based cartilage therapies.     

Identification and Structure–Activity Relationship Studies of Small‐Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1

The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small‐molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure‐ and ligand‐based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4‐aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series.     

Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) represents a major burden to global health, and refined vaccines are needed. Replication-deficient lymphocytic choriomeningitis virus (rLCMV)-based vaccine vectors against cytomegalovirus have proven safe for human use and elicited robust T cell responses in a large proportion of vaccine recipients. Here, we developed an rLCMV vaccine expressing the Mtb antigens TB10.4 and Ag85B. In mice, rLCMV elicited high frequencies of polyfunctional Mtb-specific CD8 and CD4 T cell responses. CD8 but not CD4 T cells were efficiently boosted upon vector re-vaccination. High-frequency responses were also observed in neonatally vaccinated mice, and co-administration of rLCMV with Expanded Program of Immunization (EPI) vaccines did not result in substantial reciprocal interference. Importantly, rLCMV immunization significantly reduced the lung Mtb burden upon aerosol challenge, resulting in improved lung ventilation. Protection was associated with increased CD8 T cell recruitment but reduced CD4 T cell infiltration upon Mtb challenge. When combining rLCMV with BCG vaccination in a heterologous prime-boost regimen, responses to the rLCMV-encoded Mtb antigens were further augmented, but protection was not significantly different from rLCMV or BCG vaccination alone. This work suggests that rLCMV may show utility for neonatal and/or adult vaccination efforts against pulmonary tuberculosis.     

Komplexchemisches Verhalten von N-substituierten 2-(o?Hydroxyphenyl)-Δ2-imidazolinen als Metallextraktionsmittel

The Coordinative Behaviour of N-Substituted 2-(Δ²-Imidazolin-2-yl)-phenols as Metal Extractants N-Substituted 2-(Δ²-imidazolin-2-yl)-phenols (R⁴NNOH) are obtained by the reaction of N-alkyl diaminoethane-1, 2 and 2-hydroxybenzoic acid esters. In contrast to many other copper(II) complexes with the donor set N₂O₂²⁻( A ), the species Cu(R⁴NNO)₂( B ) are easily soluble in nonpolar solvents. The reason is the monomeric square-planar structure of B , which differs from the polymeric distorted octahedral structure of A . The two maxima in the vis-spectra of Cu(R⁴NNO)₂ and Ni(R⁴NNO)₂ are assigned to the 3 dxy → 3 dx²-y² and the 3 dxz, 3 dyz → 3 dx²-y² electron transitions. The shift of these maxima, which is connected with the dissolution in chloroform, is explained by the formation of hydrogen bonds between the solvent and the N-alkylated nitrogen atoms of the ligands. ¹H-n. m. r.-spectra and solubility of the ligands and the crystal structure of Cu[(C₄H₉)NNO]₂ are described.     

The significance of microcomposites as experimental models

This paper demonstrates the usefulness of careful experimental work with model composite materials, such as thin polymeric films in which single fibers are accurately positioned, in at least two respects: to assess the validity of a theory for a given physical property, and to accurately probe the effects of various parameters on the behavior of composites. Working with such model composites has obvious advantages, such as the full control of experimental parameters, the possibility of introducing perturbative effects in a controlled way, and the possibility of verifying theoretical models in the range of low fiber content. Indeed, macroscopic composite materials contain various types of defects and perturbative effects, such as fiber misalignment or slack, fiber-poor regions, voids, etc., which bias any quantitative assessment of mechanical and physical properties, and preclude the accurate verification of theoretical schemes. One difficulty in working with microcomposite models, also recalled here, is the need for an appropriate “scaling-up” procedure to the level of macroscopic composites.     

Rheotens-mastercurves and drawability of polymer melts

In a Rheotens experiment, the tensile force needed for elongation of an extruded filament is measured as a function of the draw ratio. For thermo-rheologically simple polymer melts, the existence of Rheotens-mastercurves is proven. Rheotens-mastercurves are invariant with respect to changes in melt temperature. Also, for polymer melts with different average molar masses, but similar molar mass distribution and branching structure, Rheotens-mastercurves are invariant to changes in the average molar mass. It is shown, by testing several polyethylenes with different molar mass distribution and different long-chain branching, that Rheotens-mastercurves allow a direct and quantitative assessment of the drawability of polymer melts under actual processing conditions, i.e. under the action of a constant tensile force and including the effects of the rheological prehistory in the extrusion die.