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Most topical hemostatic agents are based on animal-derived products like collagen and gelatin. They carry the potential risk of pathogen transmission while adjustments in the production process of these materials are limited. A synthetic hemostatic agent based on polyurethane (PU) and polyethylene glycol (PEG) was developed to overcome these disadvantages. The goal of this study was to compare the degradation process of this biomaterial to collagen and gelatin hemostatic agents. Samples of the test materials were implanted subcutaneously in both rats and rabbits. The animals were sacrificed at certain time intervals up to three years and the explanted samples were microscopically assessed. The histological examination showed a comparable pattern of degradation for the different test materials. Remnants of gelatin and collagen were seen up to 26 and 39 weeks, respectively. For PU, it took up to three years before micro-particles of the material were no longer detected. All biomaterials showed a good biocompatibility and no severe foreign body reactions occurred. The good biocompatibility and predictable pattern of resorption indicate that PU can be used as a topical hemostatic agent. However, a degradation time comparable to collagen and gelatin would be favorable., (© 2015 Wiley Periodicals, Inc.)