An Injectable Hybrid Hydrogel with Oriented Short Fibers Induces Unidirectional Growth of Functional Nerve Cells

Abstract

To regenerate soft aligned tissues in living organisms, low invasive biomaterials are required to create 3D microenvironments with a structural complexity to mimic the tissue's native architecture. Here, a tunable injectable hydrogel is reported, which allows precise engineering of the construct's anisotropy in situ. This material is defined as an Anisogel, representing a new type of tissue regenerative therapy. The Anisogel comprises a soft hydrogel, surrounding magneto-responsive, cell adhesive, short fibers, which orient in situ in the direction of a low external magnetic field, before complete gelation of the matrix. The magnetic field can be removed after gelation of the biocompatible gel precursor, which fixes the aligned fibers and preserves the anisotropic structure of the Anisogel. Fibroblasts and nerve cells grow and extend unidirectionally within the Anisogels, in comparison to hydrogels without fibers or with randomly oriented fibers. The neurons inside the Anisogel show spontaneous electrical activity with calcium signals propagating along the anisotropy axis of the material. The reported system is simple and elegant and the short magneto-responsive fibers can be produced with an effective high-throughput method, ideal for a minimal invasive route for aligned tissue therapy.