In vitro and in vivo evaluation of electrospun poly (ε-caprolactone)/collagen scaffolds and Wharton's jelly mesenchymal stromal cells (hWJ-MSCs) constructs as potential alternative for skin tissue engineering

Dermal substitutes bear a high clinical demand because of their ability to promote the healing process of cutaneous wounds by reducing the healing time the appearance and improving the functionality of the repaired tissue. Despite the increasing development of dermal substitutes, most of them are only composed of biological or biosynthetic matrices. This demonstrates the need for new developments focused on using scaffolds with cells (tissue construct) that promote the production of factors for biological signaling, wound coverage, and general support of the tissue repair process. Here, we fabricate by electrospinning two scaffolds: poly(ε-caprolactone) (PCL) as a control and poly(ε-caprolactone)/collagen type I (PCol) in a ratio lower collagen than previously reported, 19:1, respectively. Then, characterize their physicochemical and mechanical properties. As we bear in mind the creation of a biologically functional construct, we characterize and assess in vitro the implications of seeding human Wharton's jelly mesenchymal stromal cells (hWJ-MSCs) on both scaffolds. Finally, to determine the potential functionality of the constructs in vivo, their efficiency was evaluated in a porcine biomodel. Our findings demonstrated that collagen incorporation in the scaffolds produces fibers with similar diameters to those in the human native extracellular matrix, increases wettability, and enhances the presence of nitrogen on the scaffold surface, improving cell adhesion and proliferation. These synthetic scaffolds improved the secretion of factors by hWJ-MSCs involved in skin repair processes such as b-FGF and Angiopoietin I and induced its differentiation towards epithelial lineage, as shown by the increased expression of Involucrin and JUP. In vivo experiments confirmed that lesions treated with the PCol/hWJ-MSCs constructs might reproduce a morphological organization that seems relatively equivalent to normal skin. These results suggest that the PCol/hWJ-MSCs construct is a promising alternative for skin lesions repair in the clinic.