Repair of superficial injury to the gastrointestinal mucosa involves the process of restitution, the rapid migration of epithelial cells across damaged areas. The effect of 45S5 bioactive glass on epithelial restitution was assessed using a novel co-culture model incorporating wounded intestinal epithelial cell monolayers and sub-epithelial myofibroblasts to simulate in vivo conditions that occur during superficial mucosal ulceration. Epithelial wound healing was not increased by culture medium conditioned with bioactive glass, with 1% (w/v) bioactive glass inhibiting cell migration. Epithelial wounds co-cultured with myofibroblasts grown on surfaces coated with 0.1% (w/v) bioactive glass increased wound healing compared with co-cultures containing no bioactive glass. Myofibroblasts grown on surfaces coated with bioactive glass secreted significantly increased amounts of basic fibroblast growth factor but did not increase epithelial cell proliferation, indicating the wound healing observed was due to restitution. These data from a model of superficial mucosal injury suggest bioactive glass may function as a stimulant of paracrine mucosal signaling networks that promotes rapid epithelial repair.