Injuries to the peripheral nervous system can cause substantial motor and sensory deficits. In the presented study, self-assembling peptide-based hydrogels are injected into a chitosan nanofiber scaffold and used as an artificial nerve graft.
REPAIRING SCIATIC NERVE INJURY WITH SELF-ASSEMBLING PEPTIDE NANOFIBER SCAFFOLD-CONTAINING CHITOSAN CONDUIT REPAIR OF SCIATIC NERVE INJURY WITH A SELF-ASSEMBLING CHITOSAN NANOFIBER SCAFFOLD
Shen X, Qu F, Pei Y, Lei S, Xia S, Liang J, Li S, Sun X and Liu L (2022) Repairing sciatic nerve injury with self-assembling peptide nanofiber scaffold-containing chitosan conduit. Front. Neurol. 13:867711. doi: 10.3389/fneur.2022.867711
Substantial motor and sensory deficits can result from injuries to the peripheral nervous system. While minor injuries usually heal on their own, more extensive damage often requires nerve grafts for repair. Currently, autologous nerve grafts are the gold standard for treating peripheral nerve defects. However, they are available in limited numbers, often resulting in donor site morbidity and increasing the risk of neuroma. Artificial nerve grafts are considered as an alternative, but so far they are often too simple to promote targeted nerve growth. Ideal properties to be fulfilled are a good biocompatibility and a sufficient similarity to the extracellular matrix (EMC). Thus, in medical research, self-assembling peptide-based hydrogels (SAPs) are considered promising candidates for neural tissue engineering.
Promising peptides include RAD, IKVAV, and KLT. RAD or RADA16-I is able to form very stable β-sheets under physiological conditions, while IKVAV resembles the EMC protein laminin and promotes neuronal adhesion, differentiation, and neurite outgrowth. KLT is a VEGF-like peptide that can also bind into VEGF receptors. This is an endothelial growth factor that triggers polarized vascularization of the bridging region.
In the presented study, two functionalized SAPs RAD/KLT and RAD/IKVAV, as well as their hybrid RAD/KLT/IKVAV, are synthesized, characterized, and evaluated for their neuronal regeneration abilities in vitro in Schwann cells (SCs) and in vivo in rats. In both cases, chitosan was used as a substitute for natural conduction pathways. In addition to its good cytocompatibility and biodegradability, its degradation products, chitosanoligosaccharides (COS), promote cell proliferation and growth.
- All three peptides exhibited a typical β-sheet structure and formed 3D nanofiber gels in the hollow lumen of the chitosan tube under physiological conditions
- Successful attachment of SCs to the surface of the peptide gels with good cell comptability, marked positive effect from SC growth in RAD/IKVAV and RAD/KLT/IKVAV, while RAD/KLT was comparable to the untreated cells
- In vivo: significantly faster functional regeneration of the nerve in RAD/KLT/IKVAV group and autograft compared with hollow chitosan tube, RAD/KLT, and RAD/IKVAV
- Histological analysis showed increased axonal and SCs regeneration in induced nerve injury in therapy with RAD/KLT/IKVAV compared with RAD/KLT and RAD/IKVAV
- Observation of the affected muscle showed marked atrophy in therapy with RAD/KLT and RAD/IKVAV, whereas nothing was seen with autograft and RAD/KLT/IKVAV
Summary: In the presented study, two laminin or VEGF-like peptides were successfully synthesized into a SAP. As a hydrogel in a chitosan tube, the combined peptide RAD/KLT/IKVAV showed a clear positive effect in nerve regeneration. It also promoted axonal regeneration and remyelination.