Bio-inspired materials for spinal cord regeneration

Abstract

This work proposes minimally invasive solutions for spinal cord regeneration after trauma. In particular, injectable biomaterials can be precisely positioned in the lesion site, and eventually repetitively injected until the complete regeneration of the tissue. For this application, a silk fibroin functionalized with collagen type IV and laminin-derived peptides, called bio-inspired multifunctionalized silk fibroin (BMS), possessing piezoelectric properties, has been synthesized. Another approach that avoids damages to the spinal cord is proposed in the thesis as a multilayer hydrogel with piezoelectric properties that acts as a bridge between the healthy parts surrounding the injury. The multilayer hydrogel consists of i) a thin-layer of gelatin and fish collagen functionalized with VEGF for blood vessels formation, which helps the survival of the cells integrating with the pia mater of the spinal cord; ii) a BMS layer, which helps the adhesion, migration of neural stem cells and induces the sprouting of the axons thanks to the presence of Netrin (a chemoattractive protein); and iii) an adhesive layer of polydopamine (PDA) to fix the patch on the injured site. The adhesive patch exhibits a potential larger than an injectable hydrogel that could guarantee a long-term cell survival and help the axons to move towards a direction. The adhesive patch will be located on the surface of the spinal cord and the chemoattractive protein will induce the sprouting of the ascendant or descendant axons in the spinal cord to reach the axons present in the patch, restoring a signal connection. Even if not final, the results indicate that the above strategy could be explored further for the regeneration of the spinal cord.