Promotion of dermal tissue engineering in a rat model using a composite 3D-printed scaffold with electrospun nanofibers and recipient-site preconditioning with an external volume expansion device.

We hypothesized that use of a composite three-dimensionally (3D) printed scaffold with electrospun nanofibers in conjunction with recipient-site preconditioning with an external volume expansion (EVE) device would enable successful dermal tissue regeneration of a synthetic polymer scaffold. Cell viability, cell infiltration, extracellular matrix deposition, scaffold contraction, and mRNA expression by dermal fibroblasts cultured on three different scaffolds, namely, 3D-printed scaffold with a collagen coating, 3D-printed scaffold with an electrospun polycaprolactone nanofiber and collagen coating, and 3D-printed scaffold with an electrospun polycaprolactone/collagen nanofiber, were measured. Before scaffold implantation, rats were treated for 2 h with an EVE device to evaluate the effect of this device on the recipient site. Cell proliferation rates were significantly higher on the 3D-printed scaffold with electrospun polycaprolactone nanofiber and collagen coating than on the other scaffolds. In cell invasion studies, the 3D-printed scaffold with electrospun polycaprolactone nanofiber and collagen coating showed better cell integration than the other scaffolds. Under stereomicroscopy, fibroblasts adhered tightly to the electrospun area, and the fibroblasts effectively produced both collagen and elastin. Rat skin treated with an EVE device exhibited increased HIF-1α protein expression and capillary neoformation compared with control skin. Invasion of CD8 cytotoxic lymphocytes surrounding the scaffold decreased when the recipient site was preconditioned with the EVE device. The composite 3D printed scaffold with electrospun nanofibers provided a favorable environment for proliferation, migration, and extracellular matrix synthesis by fibroblasts. Recipient-site preconditioning with an EVE device allowed for scaffold incorporation with less inflammation due to improved angiogenesis.