PROBLEMTo provide a less expensive and more convenient protocol for the treatment of tympanic membrane perforations (TMPs).METHODSSeveral materials were prepared and compared for TMP repair including Carbylan‐SX, Gelatin‐DTPH‐PEGDA (GX), Carbylan‐S/Gelatin‐DTPH (Carbylan‐GSX) (injectable and sponge), Gelfoam, Epifilm, and crosslinked thiolated chondroitin sulfate (CS‐DTPH‐PEGDA [CS‐SX]). Hartley pigmented guinea pigs (Elm Hill) underwent bilateral myringotomy with 1 ear left as a control and the other treated with one of the previously mentioned materials.RESULTSCarbylan‐GSX (injectable and sponge), Gelfoam with saline, and CS‐SX had the shortest time for TMP closure. Epifilm, Carbylan, and gelatin preparations resulted in closure rates similar to controls. CS‐SX showed a marked inflammatory reaction compared with controls and other materials based on neutrophil, lymphocyte, epitheloid counts, and degree of fibrosis.CONCLUSIONSThis study shows the validity of Carbylan‐GSX compared with Gelfoam as a material to promote TMP closure in an acute TMP guinea pig model.