Biodegradable and anti-swelling peptide-based supermolecule hydrogel for eliminating ROS and inhibiting inflammation in acute spinal cord injury repair.

The treatment of spinal cord injury (SCI) presents a significant global medical challenge, as the difficulties associated with neuronal regeneration are compounded by elevated levels of reactive oxygen species (ROS) and an inflammatory microenvironment that ensues following SCI. Peptide-based supramolecular hydrogels exhibit robust advantages in repairing SCI due to their natural amino acid composition and biomimetic extracellular matrix characteristics following self-assembly. However, the potential for sequence designability remains underexplored, presenting an opportunity to develop highly bioactive peptide-based biomaterials. In this study, the tripeptide GHK, which is naturally present in human plasma, was incorporated into the peptide sequence (FFFGHK) to self-assembled to injectable, biodegradable and anti-swelling supramolecular hydrogel, and concurrently, endowed the supramolecular hydrogel with powerful antioxidant and anti-inflammatory functions. In vitro experiments demonstrated that FFFGHK supramolecular hydrogel was capable to eliminating ROS, inhibiting inflammatory response, saving cell apoptosis, accelerating the adhesion and proliferation of neurons, and promoting the differentiation of neural stem cells into neurons. It is noteworthy that the FFFGHK hydrogel exhibits a promising therapeutic effect in the treatment of SCI in rats. This has been shown to significantly enhance the recovery of autonomic motor functions and signal transduction, as well as promote neuronal regeneration at the SCI site in these animals. This work presents a single-component peptide self-assembled supermolecular hydrogel system, incorporating the bioactive peptide GHK in conjunction with phenylalanine. It offers critical insights into the design of peptide-based supermolecular hydrogels for bioactive applications. STATEMENT OF SIGNIFICANCE.