Novel water-insoluble, and reduction-responsive nonwoven scaffolds were fabricated from gamma-PGA and tested in cell culture. An electrospinning method was developed to produce scaffolds of fibers with diameters of 0.05-0.5 mu m. Crosslinking of the fibers with cystamine in the presence of EDC resulted in water-insoluble gamma-PGA nonwovens with disulfide crosslinkages. These crosslinked fibers were easily decomposed under physiological conditions using L-cysteine, a biocompatible reductant. In vitro experiments with mouse L929 fibroblasts showed good adhesion onto gamma-PGA-SS fiber matrices and excellent cell proliferation. These gamma-PGA-SS nonwovens can be used as novel biocompatible and biodegradable scaffolds with reduction-responsiveness for biomedical or tissue engineering applications.