The physical and chemical properties of tissue engineering scaffolds have considerable effects on the inflammatory response at the implant site in soft tissue repair. The development of inflammation-modulating polymer scaffolds for soft tissue repair is attracting increasing attention. In this study, in order to regulate the inflammatory response at the implant site, a series of waterborne polyurethane (WPU) scaffolds with different properties were synthesized using polyethylene glycol (PEG), polycaprolactone (PCL) and poly (lactic acid)–glycolic acid copolymers (PLGAs) with three lactic acid/glycolic acid (LA/GA) ratios as the soft segments. Then, scaffolds were obtained using freeze-drying. The WPU scaffolds exhibited a porous cellular structure, high porosity, proper mechanical properties for repairing nerve tissue and an adjustable degradation rate. In vitro cellular experiments showed that the degradation solution possessed high biocompatibility. The in vitro inflammatory response of C57BL/6 mouse brain microglia (immortalized) (BV2) cells demonstrated that the LA/GA ratio of the PLGA in WPU scaffolds can regulate the external inflammatory response by altering the secretion of IL-10 and TNF-α. Even the IL-10/TNF-α of PU5050 (3.64) reached 69 times that of the control group (0.053). The results of the PC12 culture on the scaffolds showed that the scaffolds had positive effects on the growth, proliferation and differentiation of nerve cells and could even promote the formation of synapses. Overall, these scaffolds, particularly the PU5050, indeed prevent BV2 cells from differentiating into a pro-inflammatory M1 phenotype, which makes them promising candidates for reducing the inflammatory response and repairing nerve tissue. Furthermore, PU5050 had the best effect on preventing the transformation of BV2 cells into the pro-inflammatory M1 phenotype.