Injectable biocompatible hydrogels with tunable strength based on crosslinked supramolecular polymer nanofibers

Hydrogels based on supramolecular assemblies offer attractive features for biomedical applications including injectability or versatile combinations of various building blocks. We here investigate a system combining benzenetrispeptides (BTP), which forms supramolecular fibers, with polymer polyethylene oxide (PEO) forming a dense hydrophilic shell around the fibers. Hydrogels are created through the addition of a bifunctional crosslinker (CL). Rheological studies revealed that shorter hydrophobic n-hexyl spacers (BTP-C₆) lead to stronger hydrogels than BTP-C₁₂ comprising n-dodecyl chains. All hydrogels recovered rapidly (<5 s) after deformation in step-strain-measurements. We varied the crosslinker content between 0.1, 1 and 10 mol% and the overall concentration of the gelator. While the shear storage modulus of all BTP-C₁₂ hydrogels remains below 1 kPa independent of the variations, the shear storage modulus of BTP-C₆ hydrogels can be tuned from around 0.2 kPa up to almost 8 kPa. Shear rate dependent viscosity measurements further revealed similar shear thinning behavior of all hydrogels, and the calculation of extrusion parameters confirmed that the hydrogels can be easily injected even through thin cannulae. Accordingly, we injected a fluorescein-containing BTP-C₆ sample into chicken breast demonstrating the potential for application as an injectable drug depot. Furthermore, BTP-C₆ hydrogels prevent the adherence of L929 mouse fibroblasts but preserve their relative metabolic activity (>87%) during incubation on the gel when compared to cells growing on adherent surfaces. Our investigations overall reveal that the BTP-C₆ system in particular has attractive features for applications in tissue engineering or as an injectable and biocompatible drug depot.