Highly Flexible 3D Printed Gelatin-Pluronic F127 Scaffolds Seeded with Schwann Cells toward Nerve Regeneration

Peripheral nerve injury increasingly affects people around the world, leading to very incapacitating conditions with the loss of motor and sensory functions. Combining biomaterials with glial cells is particularly promising to reconnect injured axons to their original target, as they represent a supportive environment facilitating cell and axonal growth. Neural tissue engineering using biomimetic soft scaffolds often faces challenges related to handling, suturability, and integration into the host tissue. This study aimed to develop a soft and flexible biomimetic scaffold that supports colonization with a high density of glial Schwann cells (SCs). The strategy consists of printing tubular multichannel (500 to 1000 μm channels) nerve guides (NG) (5 × 5 mm) presenting an anisotropic architecture using a high-resolution stereolithography printing process. To this aim, the synthesis of photosensitive methacrylated gelatin (GelMA) inks was optimized and combined with various ratios of dimethacrylated F127 Pluronic. We showed that the physicochemical and mechanical properties of the printed hydrogels can be controlled by polymer concentrations and ratios. Specifically, in a 12:3 GelMA:F127DMA ratio, Pluronic provides enhanced flexibility while maintaining softness similar to nerve tissues. Importantly, gelatin-Pluronic scaffolds better withstand handling than gelatin scaffolds, as demonstrated by a higher strain at break in compression assays. Moreover, strain at break in suturing experiments was more than doubled with GelMA:F127DMA (35%) hydrogels in contrast to fragile and brittle gelatin-only scaffolds (15%). Schwann cells adhere, proliferate, and remain viable over 7 days within the channels demonstrating that these cellularized gelatin-Pluronic nerve guides hold significant promise for nerve regeneration.