Expanded 3D Nanofiber Scaffolds: Cell Penetration, Neovascularization, and Host Response

Herein, a robust method to fabricate expanded nanofiber scaffolds with controlled size and thickness using a customized mold during the modified gas-foaming process is reported. The expansion of nanofiber membranes is also simulated using a computational fluid model. Expanded nanofiber scaffolds implanted subcutaneously in rats show cellular infiltration, whereas non-expanded scaffolds only have surface cellular attachment. Compared to unexpanded nanofiber scaffolds, more CD68⁺ and CD163⁺ cells are observed within expanded scaffolds at all tested time points post-implantation. More CCR7⁺ cells appear within expanded scaffolds at week 8 post-implantation. In addition, new blood vessels are present within the expanded scaffolds at week 2. The formed multinucleated giant cells within expanded scaffolds are heterogeneous expressing CD68, CCR7, or CD163 markers. Together, the present study demonstrates that the expanded nanofiber scaffolds promote cellular infiltration/tissue integration, a regenerative response, and neovascularization after subcutaneous implantation in rats. The use of expanded electrospun nanofiber scaffolds offers a promising method for in situ tissue repair/regeneration and generation of 3D tissue models/constructs.