Superficial bladder cancer is often treated by removing the cancerous portion of the bladder wall combined with immuno-chemotherapy; in more extreme cases, it is often necessary to remove the entire bladder wall. This diagnosis brings an obvious need for bladder tissue replacement designs with a high degree of efficacy. Since bladder cells are accustomed to interacting with extracellular matrix proteins having dimensions on the nanometer scale, this study aimed to design the next generation of tissue-engineered bladder replacement constructs with nanometer (less than 100 nm) surface features. For this purpose, porous and biodegradable PLGA and PU scaffolds were treated with various concentrations of NaOH or HNO3, respectively, for various periods of time to create nanometer surface roughness. Resulting surface properties were characterized using SEM (to visualize scaffold properties) and BET. Cell experiments conducted on these polymeric scaffolds provided evidence of enhanced bladder smooth muscle cell attachment, growth, and elastin/collagen production (critical extracellular matrix proteins in the bladder tissue regeneration process) as surface feature dimensions were reduced into the nanometer regime. In vivo augmentation surgeries with nano-structured PLGA and PU patches will provide further information regarding total bladder capacity, anastomotic integrity, burst pressure, epithelialization, muscular ingrowth, and neovascularization. In vitro and in vivo proof of material usefulness and technique would provide urologists with a readily accessible graft for bladder tissue replacement applications.