Main-Chain Liquid Crystalline Networks Synthesized by Click Chemistry as 2D/3D Cell Scaffolds

Liquid crystalline (LC) polymer networks (LCNs) couple polymer chain organization to molecular ordering, the switching of which has been shown to impart stimuli-responsive properties, including actuation and one-way shape memory, to the networks. Here, main- chain LCNs were prepared with hydrophilic spacers using alkyne-azide cycloaddition chemistry to promote interaction with water, and the resulting LCNs were found to order into liquid crystalline phases in the dry and hydrated states. The use of low molecular weight polyether spacers was found to prevent their crystallization within the LC network, and adjusting mesogen composition to enhance its LC phase stability allowed the use of spacers with larger molecular weights and pendant groups. The click chemistry approach led to high gel fraction materials, the workup of which resulted in networks that displayed no difference in cellular toxicity compared to tissue culture plastic control materials. This work led to the hypothesis that tuning strength of the LC phase with hydrophilicity of the spacer could result in water soluble polymers that could be crosslinked in an aqueous medium to generate LC hydrogels. To that end, linear main-chain LC polymers were prepared with azide-terminated polyethylene oxide spacers using alkyne-azide cycloaddition click chemistry. The resulting polymers were water-soluble and were found to organize into LC phases when dry. The water-soluble polymers were then crosslinked in aqueous media by strain-promoted alkyne-azide cycloaddition, which enabled crosslinking without the addition of catalyst or generation of by-products. The resulting networks showed LC ordering in both dry and hydrated states with high water content. Importantly, the chemistry was found to be compatible with cell encapsulation, and human mesenchymal stem cells (hMSCs) cultured within the networks showed excellent viability. hMSC proliferation proceeded at a faster rate in LC hydrogels compared to non-LC hydrogels, enabling applications as anisotropic and responsive substrates for tissue engineering and regenerative medicine.