Simulation of DBS, DBS-COOH, and DBS-CONHNH2 as Hydrogelators.

The organic gelator 1,3(R):2,4(S)-dibenzylidene-d-sorbitol (DBS) self-organizes to form a 3D network at relatively low concentrations in a variety of nonpolar organic solvents and polymer melt. DBS could be transformed into a hydrogelator by introduction of hydrophilic groups, which facilitate its self-assembly in an aqueous medium. In this work, we have investigated the hydrogelators DBS-COOH and DBS-CONHNH2 and the organogelator DBS by molecular modeling. We have used quantum mechanics (QM) to elucidate the preferred geometry of one molecule and a dimer of each of the gelators and molecular dynamics (MD) to simulate the pure gelators and their mixtures with water. The results of the simulation indicate that the interaction between DBS-COOH molecules is the strongest of the three and its water compatibility is the highest. Therefore, DBS-COOH seems to be a better hydrogelator than DBS-CONHNH2 and DBS. Intermolecular H-bonding interactions are formed between DBS, DBS-COOH, and DBS-CONHNH2 molecules as pure substances, and they dramatically decrease in the presence of water. In contrast, the intramolecular interactions increase in water. This result indicates that in aqueous environment the molecular structure tends to be more rigid and fixed in the preferred conformation. The most significant intramolecular interaction is formed between O3 acetal and H-O6 groups. Due to the H-bonds, DBS, DBS-COOH, and DBS-CONHNH2 molecules form a rigid structure similar to that of liquid crystal forming molecules, which might explain their tendency to create nanofibrils. It was found that the aromatic rings do not contribute significantly to the inter- and intramolecular interactions. Their main role is probably to stiffen the molecular structure.

De Novo Design of Functional Coassembling Organic-Inorganic Hydrogels for Hierarchical Mineralization and Neovascularization.

Synthetic nanostructured materials incorporating both organic and inorganic components offer a unique, powerful, and versatile class of materials for widespread applications due to the distinct, yet complementary, nature of the intrinsic properties of the different constituents. We report a supramolecular system based on synthetic nanoclay (Laponite, Lap) and peptide amphiphiles (PAs, PAH3) rationally designed to coassemble into nanostructured hydrogels with high structural integrity and a spectrum of bioactivities. Spectroscopic and scattering techniques and molecular dynamic simulation approaches were harnessed to confirm that PAH3 nanofibers electrostatically adsorbed and conformed to the surface of Lap nanodisks. Electron and atomic force microscopies also confirmed an increase in diameter and surface area of PAH3 nanofibers after coassembly with Lap. Dynamic oscillatory rheology revealed that the coassembled PAH3-Lap hydrogels displayed high stiffness and robust self-healing behavior while gas adsorption analysis confirmed a hierarchical and heterogeneous porosity. Furthermore, this distinctive structure within the three-dimensional (3D) matrix provided spatial confinement for the nucleation and hierarchical organization of high-aspect ratio hydroxyapatite nanorods into well-defined spherical clusters within the 3D matrix. Applicability of the organic-inorganic PAH3-Lap hydrogels was assessed in vitro using human bone marrow-derived stromal cells (hBMSCs) and ex vivo using a chick chorioallantoic membrane (CAM) assay. The results demonstrated that the organic-inorganic PAH3-Lap hydrogels promote human skeletal cell proliferation and, upon mineralization, integrate with the CAM, are infiltrated by blood vessels, stimulate extracellular matrix production, and facilitate extensive mineral deposition relative to the controls.

Supramolecular Self-Assembly To Control Structural and Biological Properties of Multicomponent Hydrogels.

Self-assembled nanofibers are ubiquitous in nature and serve as inspiration for the design of supramolecular hydrogels. A multicomponent approach offers the possibility of enhancing the tunability and functionality of this class of materials. We report on the synergistic multicomponent self-assembly involving a peptide amphiphile (PA) and a 1,3:2,4-dibenzylidene-d-sorbitol (DBS) gelator to generate hydrogels with tunable nanoscale morphology, improved stiffness, enhanced self-healing, and stability to enzymatic degradation. Using induced circular dichroism of Thioflavin T (ThT), electron microscopy, small-angle neutron scattering, and molecular dynamics approaches, we confirm that the PA undergoes self-sorting, while the DBS gelator acts as an additive modifier for the PA nanofibers. The supramolecular interactions between the PA and DBS gelators result in improved bulk properties and cytocompatibility of the two-component hydrogels as compared to those of the single-component systems. The tunable mechanical properties, self-healing ability, resistance to proteolysis, and biocompatibility of the hydrogels suggest future opportunities for the hydrogels as scaffolds for tissue engineering and drug delivery vehicles.