IKVAV peptide-containing hydrogel decreases fibrous scar after spinal cord injury by inhibiting fibroblast migration and activation

Abstract

Fibrous scar is one of the major factors that hinder functional recovery in patients with spinal cord injury (SCI). Studies have shown that the laminin α1 peptide chain ile-les-val-ala-Val (IKVAV) promoted axonal growth and motor function recovery in rats after SCI. However, whether IKVAV could ameliorate SCI via reducing the formation of fibrous scar was not clear. A SCI model was constructed by transecting the rat spinal cord with a scalpel and implanting poly (N-propan-2-ylprop-2-enamide) (PNIPAM)-b-poly (AC-PEG-COOH) (PNPP) or PNIPAM-b-poly (AC-PEG-IKVAV) (PNPP-IKVAV) hydrogel. 14 days later hematoxylin-eosin staining and immunohistochemical staining were used to assess the effect of PNPP-IKVAV on scar formation. The effect of PNPP-IKVAV on endoplasmic reticulum (ER) stress was investigated by immunohistochemical staining. NIH-3T3 cells were used for in vitro scratching experiments and a transforming growth factor 1 (TGF-β1) activation model was constructed to assess the role of PNPP-IKVAV. In this study, PNPP-IKVAV inhibited fibroblast migration and suppressed TGF-β1 activation and ER stress (ERS) to reduce the extracellular matrix secretion by fibroblasts.