A cellulose-based skin adhesive hydrogel incorporating N-acetyl-seryl-aspartyl-lysyl-proline peptide for enhanced wound healing and scar prevention in rabbit scar ear model in vivo.

Abstract

BACKGROUND: biocompatible hydrogel glue with vigorous wet tissue adhesion has attracted considerable attention for controlling severe hemorrhage and enhancing wound healing process. In this study, anti-scar hemostatic glue was prepared using mussel-inspired catechol-based strategy for bleeding control, healing promotion and scar prevention. METHODS: first, oxidized carboxymethylcellulose (OCMC) encoded with dopamine to obtain Dopa-OCMC polymer. Then, the polyallylamine (PAA) conjugated to OCMC or Dopa-OCMC by Schiff base reaction and then polymerized Dopa-OCMC-PAA strength sealant and OCMC-PAA hydrogel glue, containing anti-fibrotic N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) peptide were fabricated. The properties of hydrogels were fully characterized in vitro and subsequently their antifibrotic effects were evaluated on rabbit ear fibrotic model in vivo by histological analysis of epidermal thickness & scar index, and gene expression. RESULTS: outcomes showed that both adhesives demonstrated proper swelling, degradation rate, appropriate release profile as well as potential for cell proliferation, and promising mechanical strength but Dopa-OCMC-PAA exhibited significantly higher overall performance than the other adhesives. Moreover, hemostatic effect on the hepatic bleeding of mouse model exhibited faster bleeding stop in Dopa-OCMC-PAA glue. Besides, Ac-SDKP treated fibroblast significantly showed elevation of MMP-1 and MMP-3 and reduction of collagen gene expression in vitro. Moreover, molecular and histological evaluations significantly demonstrated that Ac-SDKP and dopamine reduced scar formation in rabbit treated ear by showing decreased scar index (SEI), cellularity and collagen disorganization on stained dermis and upregulation of MMP-1 and MMP-3 and downregulation of collagen genes in treated wounds in vivo. CONCLUSION: the results displayed that Dopa-OCMC-PAA/Ac-SDKP hydrogel glue would be a promising platform for the treatment of hemorrhage and hypertrophic scar in clinical setting.