Engineering integrin signaling for promoting embryonic stem cell self-renewal in a precisely defined niche.

We present development and use of a 3D synthetic extracellular matrix (ECM) analog with integrin-specific adhesion ligands to characterize the microenvironmental influences in embryonic stem cell (ESC) self-renewal. Transcriptional analysis of 24 integrin subunits followed by confirmation at the translational and functional levels suggested that integrins alpha(5)beta(1), alpha(v)beta(5), alpha(6)beta(1) and alpha(9)beta(1) play important roles in maintenance of stemness in undifferentiated mouse ESCs. Using the well-defined matrix as a tool to activate integrins alpha(5)beta(1) plus alpha(v)beta(5), alpha(6)beta(1) and alpha(9)beta(1), individually and in combination, differential integrin activation was demonstrated to exert exquisite control over ESC fate decisions.

Micelles for delivery of nitric oxide.

We designed block copolymer pro-amphiphiles and amphiphiles for providing very long-term release of nitric oxide (NO). A block copolymer of N-acryloylmorpholine (AM, as a hydrophile) and N-acryloyl-2,5-dimethylpiperazine (AZd, as a hydrophilic precursor) was synthesized. The poly(N-acryloyl-2,5-dimethylpiperazine) (PAZd) is water-soluble, but chemical reaction of the secondary amines with NO to form a N-diazeniumdiolate (NONOate) converts the hydrophilic PAZd into a hydrophobic poly(sodium-1-(N-acryloyl-2,5-dimethylpiperazin-1-yl)diazen-1-ium-1,2-diolate) (PAZd.

Biomimetic PEG hydrogels crosslinked with minimal plasmin-sensitive tri-amino acid peptides.

Semi-synthetic, proteolytically degradable polymer hydrogels have proven effective as scaffolds to augment bone and skin regeneration in animals. However, high costs due to expensive peptide building blocks pose a significant hurdle towards broad clinical usage of these materials. Here we demonstrate that tri-amino acid peptides bearing lysine (or arginine), flanked by two cysteine residues for crosslinking, are adequate as minimal plasmin-sensitive peptides in poly(ethylene glycol)-based hydrogels formed via Michael-type addition.

Thermosensitive nanospheres with a gold layer revealed as low-cytotoxic drug vehicles.

In this paper, the positive effect of a gold layer on cell viability is demonstrated by examining the results given by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfop henyl)-2H-tetrazolium (MTS) assay and two-color cell fluorescence viability (TCCV) assay. These cytotoxicity tests were performed with human cervical adenocarcinoma cells (HeLa cell line) and transformed African green monkey kidney fibroblast cells (Cos-7 cell line). To fabricate the nanostructures as drug vehicles, first, poly(l,l-lactide-co-ethylene glycol) (PLLA-PEG) and poly(N-isopropylacrylamide-co-D,D-lactide) (PNIPAAm-PDLA) were synthesized, and then two kinds of thermosensitive nanospheres comprising "shell-in-shell" structures without a gold layer (PLLA-PEG@PNIPAAm-PDLA) and with a gold layer (Au@PLLA-PEG@PNIPAAm-PDLA) were constructed by a modified double-emulsion method (MDEM).