Enhanced wound healing via stem cell migration using a substance P1-loaded cross-linked small intestinal submucosa scaffold.

This study investigated the potential of enhancing stem cell-mediated wound healing using a novel dressing composed of chemoattractant Substance P1 (SP1), a peptide analog of Substance P, incorporated into a cross-linked small intestinal submucosa (Cx-SIS) scaffold. Cx-SIS scaffolds were optimized for porosity, surface roughness, and degradation rate by adjusting the cross-linker concentration. While SP1 was rapidly released from non-cross-linked (N-SIS) scaffolds, the Cx-SIS scaffolds demonstrated a controlled burst release. Cx-SIS scaffolds maintained structural integrity for 14 days, whereas N-SIS dissolved within 1 days, leading to reduced effectiveness. SP1 + Cx-SIS scaffolds significantly enhanced the migration of human mesenchymal stem cells (hMSCs), surpassing both the Cx-SIS and control groups. In vivo studies revealed that both Cx-SIS and SP1 + Cx-SIS scaffolds effectively migrated stem cells, accelerated wound healing, and reduced scar formation. Histological analysis showed that the SP1 + Cx-SIS scaffold accelerated tissue regeneration and collagen deposition during healing, while immunofluorescence staining indicated improved hMSC migration and angiogenesis. In conclusion, SP1 + Cx-SIS is an effective scaffold for wound healing, particularly when combined with SP1 peptide, offering a promising approach for developing clinical-centered wound healing strategies through enhanced stem cell migration.