Polyurethane-based tissue fillers useful for treating and/or augmenting tissue, as well as acting as a biological scaffold that promotes cell in-ingrowth and tissue integration, are disclosed, as are quick-setting, injectable precursors of such tissue fillers. Such tissue fillers generally comprise (1) a polyurethane and (2) a particulate acellular tissue matrix. Also disclosed are methods of treating and/or augmenting tissues using such tissue fillers, particularly voids in human tissue such as anal fistulae or hernias.