A significant problem affecting electrospun nanofibrous tissue scaffolds is poor infiltration of cells into their three-dimensional (3D) structure. Environmental and physical manipulation, however, can enhance cellular infiltration into electrospun scaffolds. In this work, RGD-modified alginate mats with increased thickness and porosity were achieved by pairing high humidity electrospinning with post-processing ultra-sonication. RGD-modified alginate, polyethylene oxide (PEO), and an FDA-approved, nonionic surfactant blends were electrospun in 20 and 50% relative humidity conditions. Mats electrospun in high humidity conditions resulted in significantly increased mat thickness and decreased fiber diameters. The mats' alginate content was then isolated via ionic crosslinking and PEO/surfactant extraction. Finally, the alginate-only mat was post-processed by ultrasonication to further enhance its cross-sectional thickness. Cell morphology, proliferation, and infiltration into the scaffolds were evaluated by seeding fibroblasts onto the alginate mat. Cell spreading, growth and infiltration improved with increased humidity and ultrasonication. This approach shows great promise for the design of cellpermeable nanofibrous scaffolds for tissue-engineering applications.