A Fibrous and Porous Nature of Hydrogels Promotes Directed Migration of Schwann Cells

Introduction: Hydrogel fillings have been successful in enhancing artificial conduits for nerve injuries, but the ideal hydrogel is yet to be found. Its discovery is impeded by an overflow of available products as well as a lack of in vitro experiments that fully analyze the effects of these hydrogels on cells crucial for nerve regeneration. Materials and Methods: This study investigated various hydrogels advertised for peripheral nerve regeneration. Schwann cells were seeded on the hydrogels and their morphology, viability, proliferation and migration were examined in vitro. Results: Our results demonstrated that the basement membrane extract hydrogel Cultrex® 3D Culture Matrix® (Trevigen) promoted elongated morphology and directed migration in SCs. To elucidate the possible reasons behind this, detailed material characterizations of the hydrogels were conducted and identified highly bundled networks of fibres in Cultrex® 3D Culture Matrix® as well as strain-stiffening. In a next step, we further analyzed two more hydrogels consisting of solely one component of Cultrex® 3D Culture Matrix® respectively namely laminin and collagen and found that the SCs also migrated more directed in the laminin hydrogel but not in the collagen hydrogel. Interestingly, out of the two hydrogels only the laminin hydrogel showed a similar fibrous surface roughness to Cultrex® 3D Culture Matrix® and also exhibited strain-stiffening. This indicates a correlation between a fibrous nature of hydrogels, strain-stiffening and directed migration in Schwann cells. Conclusion: These experiments provide a unique systematic assessment of various hydrogels in respect to their material properties and their effect on cells thereby paving the path for the future manufacturing of tailored biomaterials.