Graduate Student Ajou university Ajou university/SUWON, Republic of Korea
Abstract: Regeneration of skin tissue is vital for wound healing, and endogenous stem cell-based in-situ regeneration has drawn significant attention due to its potential to enhance tissue repair by recruiting the body’s own stem cells. However, existing wound dressings often fail to effectively control the release of bioactive molecules or provide sustained structural support for cellular recruitment. To address these gaps, this study developed SP1-functionalized cross-linked small intestinal submucosa (Cx-SIS) scaffolds to enhance stem cell recruitment and tissue regeneration. SP1, a chemoattractant peptide analog of Substance P, was incorporated into Cx-SIS scaffolds optimized for porosity, surface roughness, and degradation rate by adjusting cross-linker concentrations. Non-cross-linked (N-SIS) scaffolds exhibited rapid SP1 release, resulting in uncontrolled diffusion, while Cx-SIS scaffolds provided a controlled burst release and maintained their structural integrity for 14 days, unlike N-SIS, which degraded within 2 days. In vitro, SP1-functionalized Cx-SIS scaffolds significantly enhanced rat mesenchymal stem cell (rMSC) migration compared to non-functionalized scaffolds and controls. In vivo experiments demonstrated that SP1+Cx-SIS scaffolds accelerated rMSC recruitment, improved tissue regeneration, and reduced scar formation. Histological and immunofluorescence analyses confirmed enhanced collagen deposition, tissue remodeling, and angiogenesis. This study demonstrates that SP1+Cx-SIS scaffolds effectively enhance stem cell recruitment and wound healing by integrating the chemoattractant properties of SP1 with the structural advantages of cross-linked scaffolds. These findings provide a novel approach for regenerative medicine and advanced wound care, offering a clinically relevant platform to improve patient outcomes and support endogenous tissue repair.
