Molecular-Scale Tuning of Low-Molecular-Weight Gelators Controls Supramolecular Assembly and Directs Human...

We report the synthesis and characterization of a simple alcohol-functionalized low-molecular-weight gelator (LMWG) based on a 1,3:2,4-dibenzylidenesorbitol scaffold (DBS-CH₂OH) and explore its self-assembly in comparison to acylhydrazide-functionalized DBS-CONHNH₂. DBS-CH₂OH forms a stiffer, highly organized, less-soluble self-assembled hydrogel, with a different assembly mode and much higher entropy/enthalpy of dissociation. On mixing, the LMWGs co-assemble into gel nanofibers with similar thermodynamics to DBS-CONHNH₂. DBS-CH₂OH is an excellent scaffold for the growth of human mesenchymal stem cells (hMSCs), which exhibit extended spread-shaped morphologies on the gel surface. In contrast, for DBS-CONHNH₂, hMSCs have a rounded morphology and penetrate into the softer gel. A simple functional group change on the LMWG, therefore, leads to a remarkable change in cell growth outcomes. When hMSCs are grown on the co-assembled gel, they have the rounded morphology characteristic of DBS-CONHNH₂ but remain on the gel surface, like DBS-CH₂OH. The multi-component gel thus shares characteristics of the individual LMWGs, with hMSC growth being controlled by factors like structure, stiffness, and dynamics. This work demonstrates how chemical manipulation of gels based on deceptively simple LMWGs can have profound impacts in biomaterials engineering.