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

Abstract

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 the polymer polyethylene oxide (PEO) forming a dense hydrophilic shell around the fibers. Hydrogels are created through addition of a bifunctional crosslinker (CL). Rheological studies revealed that shorter hydrophobic n-hexyl spacers (BTP-C6) lead to stronger hydrogels than the BTP-C12 comprising n-dodecyl chains. All hydrogels recover 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 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 calculation of extrusion parameters confirms that the hydrogels can easily be injected even through thin cannulas. Accordingly, we injected a fluorescein containing BTP-C6 sample into chicken breast demonstrating the potential for application as injectable drug depot. Furthermore, BTP-C6 hydrogels prevent 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 particularly the BTP-C6 system has attractive features for applications in tissue engineering or as injectable and biocompatible drug depot.