Construction of self-assembled nanostructure-based tetraphenylethylene dipeptides: supramolecular nanobelts as biomimetic hydrogels for cell adhesion and proliferation.

Supramolecular fluorescent materials with aggregation-induced emission (AIE) characteristics have promising applications as fluorescent probes for bio and chemosensors. In this study, a versatile low molecular weight tetraphenylethylene dipeptide hydrogelator (TPE-YY) with efficient AIE characteristics was developed, which was able to form hydrogels in a broad pH range from 3.7 to 10.2. The self-assembly of this hydrogel is completely pH-dependent, with significant structural transitions from high to low pH. At a relatively high pH value (10.2), a weak transparent hydrogel with an entangled network of nanofibers was obtained, while upon neutralization (pH 7.2) with dilute HCl, a stable semi-transparent gel with twisted nanobelts was formed. When the pH of the hydrogel was reduced to below 5.7, a turbid viscous gel and precipitation appeared with the thickening of the nanobelts. Surprisingly, the hydrogel resulting from the glucono-δ-lactone triggered gel showed only nanofibers independent of pH. The nature of the hydrogels and the nanostructures at different pH values were thoroughly examined and discussed via oscillatory rheology, electron microscopy and various spectroscopic techniques {1HNMR, 2D-NMR, Fourier transform infrared (FTIR) and Circular dichroism (CD)}. Interestingly, the self-assembled hydrogel exhibited excellent biocompatibility over 95% using hydrogel leachables on two different cell lines, 3A6 (human MSCs) and L929 (mouse fibroblast cells). Moreover, the self-assembled nanobelts formed at neutral pH showed excellent cell adhesion and proliferation of 3A6 cells, whereas the nanofibers showed poor cell adhesion and proliferation. Overall, we demonstrate the importance of chemical design for the formation of self-assembled nanobelts and supramolecular hydrogels at physiological pH with selective cell adhesion and proliferation, presenting a promising applications in tissue engineering and regenerative medicine.

Glucosamine-Based Supramolecular Nanotubes for Human Mesenchymal Cell Therapy.

Herein, we demonstrate an example of glucosamine-based supramolecular hydrogels that can be used for human mesenchymal cell therapy. We designed and synthesized a series of amino acid derivatives based on a strategy of capping d-glucosamine moiety at the C-terminus and fluorinated benzyl group at the N-terminus. From a systematic study on chemical structures, we discovered that the glucosamine-based supramolecular hydrogel [pentafluorobenzyl (PFB)-F-Glu] self-assembled with one-dimensional nanotubular structures at physiological pH. The self-assembly of a newly discovered PFB-F-Glu motif is attributed to the synergistic effect of π-π stacking and extensive intermolecular hydrogen bonding network in aqueous medium. Notably, PFB-F-Glu nanotubes are proven to be nontoxic to human mesenchymal stem cells (hMSCs) and have been shown to enhance hMSC proliferation while maintaining their pluripotency. Retaining of pluripotency capabilities provides potentially unlimited source of undifferentiated cells for the treatment of future cell therapies. Furthermore, hMSCs cultured on PFB-F-Glu are able to secrete paracrine factors that downregulate profibrotic gene expression in lipopolysaccharide-treated human skin fibroblasts, which demonstrates that PFB-F-Glu nanotubes have the potential to be used for wound healing applications. Overall, this article addresses the importance of chemical design to generate supramolecular biomaterials for stem cell therapy.