Chapter 14 - Self-Assembling Peptides Mediate Neural Regeneration

Abstract

Self-assembling peptides (SAPs) are a special class of ionic-complementary peptides that consist of alternating hydrophilic and hydrophobic amino acid residues. These peptides can assemble into well-ordered nanostructures when they are introduced into solutions of electrolytes. Traumatic brain or spinal cord injury or neurosurgical procedures often result in tissue loss and then the formation of a cavity or gap due to the mechanical forces and a cascade of secondary events. In injured peripheral nerves, the gap formation in the peripheral nerve is not only due to the tissue loss, but also to the elastic retraction of the nerve and the movement of the joint that will increase the final length of the gap. Cavity or gap formation is a major obstacle in neural regeneration. As a kind of novel biomaterial that can create nanofiber scaffolds, SAPs have been widely used for repairing tissue defects and have shown great promise in neural regeneration. Compared with conventional biomaterials, SAPs have several major advantages, including: mimicking the native extracellular matrix, which provides a true three-dimensional microenvironment for tissue regeneration; having excellent physiological compatibility, as well as minimal cytotoxicity; achieving immediate hemostasis without involvement of the blood coagulative cascade; and acting as a cell- and/or drug-delivery system. Initiated by using SAPs nanofiber scaffold in the treatment of injuries of optic tract, a series of research projects in our group has focused on the combinational strategies of SAP-based tissue engineering in the repair of both central and peripheral nervous systems. In brief, modeling with acute traumatic brain injury models in the midbrain or sensory-motor cortex, RADA16-I SAPs nanofiber scaffold was found to bridge the injury gap, to reconstruct the lesion cavity, and/or to promote knitting of the wounded tissues. After being transplanted into the injured spinal cord, SAPs combined with neural progenitor cells, Schwann cells or permeable RhoA inhibitor not only reconnnected the injured cord gap, but also elicited significant axonal regeneration and functional recovery. This SAP conduit also effectively reduced the inflammation and glial scarring in the perilesion area. With respect to the peripheral nerve injury, the SAP-enhanced nerve conduit was tested to repair a 10-mm-long deficit of transected sciatic nerve. When histomorphology, retrograde-labeling, and locomotor functional assessments were examined, the SAPs’ nanofiber conduit demonstrated significant therapeutic effects on the axonal regeneration, remyelination, target reinnervation, and functional recovery.