Collagen-elastin dermal scaffolds enhance tissue regeneration and reduce scarring in preclinical models.

Severe scarring is an inevitable consequence of large full-thickness skin wounds, often leading to long-term complications that affect patients' well-being and necessitate extended medical interventions. While autologous split-thickness skin grafts remain the clinical standard for wound treatment, they frequently result in contractures, excessive scarring, and the need for additional corrective procedures. To address these challenges, bioengineered skin substitutes capable of promoting efficient healing while reducing complications are highly desirable. Elastin, an essential component of the extracellular matrix, plays a crucial role in restoring tissue elasticity and regulating scar formation during wound healing. This study explores the impact of two distinct elastin-derived components, produced through acidic and basic hydrolysis, on wound repair. We developed and characterized collagen-based scaffolds enriched with these elastin hydrolysates and assessed their influence on different types of human skin fibroblasts, including fetal, eschar-derived, and healthy adult dermis-derived fibroblasts. Furthermore, we evaluated their therapeutic potential in a preclinical rat model. Our findings indicated that fetal fibroblasts exhibited the most pronounced extracellular matrix deposition and cellular infiltration within the scaffolds, followed by eschar fibroblasts and, lastly, healthy adult cells. The incorporation of elastin into collagen scaffolds led to a reduction in α-SMA protein expression, a biomarker of fibrosis, compared to collagen-only scaffolds. Notably, collagen scaffolds supplemented with elastin hydrolysate from basic hydrolysis demonstrated the most promising outcomes for scarless healing, characterized by minimal wound contraction, enhanced extracellular matrix formation, and increased neovascularization.