Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision

Abstract

Nanotechnology is often associated with materials fabrication, microelectronics, and microfluidics. Until now, the use of nanotechnology and molecular self assembly in biomedicine to repair injured brain structures has not been explored. To achieve axonal regeneration after injury in the CNS, several formidable barriers must be overcome, such as scar tissue formation after tissue injury, gaps in nervous tissue formed during phagocytosis of dying cells after injury, and the failure of many adult neurons to initiate axonal extension. Using the mammalian visual system as a model, we report that a designed self-assembling peptide nanofiber scaffold creates a permissive environment for axons not only to regenerate through the site of an acute injury but also to knit the brain tissue together. In experiments using a severed optic tract in the hamster, we show that regenerated axons reconnect to target tissues with sufficient density to promote functional return of vision, as evidenced by visually elicited orienting behavior. The peptide nanofiber scaffold not only represents a previously undiscovered nanobiomedical technology for tissue repair and restoration but also raises the possibility of effective treatment of CNS and other tissue or organ trauma.

Peptide-based biopolymers in biomedicine and biotechnology

“…It was shown that these self-assembled hydrogels can support cell attachment of a variety of mammalian cells, including endothelial cells [233], osteoblasts [234], neural cells [227,235], hepatocytes [232], and chondrocytes [225]. Kisiday et al used oligopeptides containing leucine, lysine, and aspartic acid ( Figure 19a) to form hydrogel matrices that supported the growth and accumulation of chondrocytes (Figure 19b).…”

“…Zhang et al have synthesized short oligopeptides having 12 to 16 amino acids that spontaneously form stable β-sheet structures under physiological solution conditions [220][221][222][223][224][225][226][227][228][229][230][231][232][233][234][235]. As shown in Figure 19a, these ionic selfcomplementary oligopeptides have amphiphilic character; one face of the molecule consists of nonpolar, hydrophobic amino acids (such as Ala, Phe, or Leu), and the other face consists of alternating oppositely charged amino acids (such as positively charged Lys or Arg and negatively charged Asp or Glu).…”

Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

“…Peptides have recently been used to generate tubular, fibrillar, micellar, or vesicular nanostructures due their amphiphilic nature. [14][15][16][17] For example, peptides with a hydrophilic head and a hydrophobic tail spontaneously self-assemble to form vesicular structures in aqueous solution. 18 Peptide aggregation may alter the overall conformation and presentation of the amino acid sequence that interacts with cell surface receptors, which adversely affects the osteoinductive potential of the peptide.…”

Novel Nanomaterials for Clinical Neuroscience

“…Such networks mimic the neuron-specific extracellular matrix and induce very rapid differentiation of cells into neurons, without stimulation of the growth of astrocytes. In another publication, a nanofiber scaffold of self-assembling peptide (RADA) was shown to induce regeneration of axons with sufficient density to promote functional return of vision (Ellis-Behnke et al 2006). …”