Engineering vascularized dermal grafts by integrating a biomimetic scaffold and Wharton's jelly MSC-derived endothelial cells

Tissue engineering aims to generate functional tissue constructs with the necessary scaffold properties for cell colonization and the establishment of a vascular network. However, treatment of tissue defects using synthetic scaffolds remains a challenge mainly due to insufficient and slow vascularization. Our previous study developed a macroporous silk fibroin scaffold with a nanofibrous microstructure, and demonstrated that the nanofibrous structure can promote the viability of endothelial cells (ECs) and guide cell migration. Further studies are needed to clarify the effect of scaffold microstructures on cell-mediated vascularization. Here, we investigated the efficacy of EC-seeded nanofibrous scaffolds in improving vascularization in vivo. ECs derived from induced human Wharton's Jelly mesenchymal stem cells served as a potential source for cell transplantation. The cell-seeded scaffolds were implanted into dermal defects of SD rats, demonstrating that the multiscale hierarchical design significantly improved the capacity of transplanted cells to promote and accelerate neovascularization and dermal reconstruction via enhancing cell infiltration, collagen deposition and growth factor expression. Our findings provide new insight into the development of degradable macroporous composite materials with 3D microstructures as tissue engineering scaffolds with enhanced vascularization functions, and also provide new treatment options for cell transplantation.