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It is effective with ongoing systemic antithrombotic therapy and can be used in all types of bone\u2010related surgery, for example, in dental surgery. Thrombin\u2010loaded poly(<jats:sc>D<\/jats:sc>,<jats:sc>L<\/jats:sc>\u2010lactide\u2010<jats:italic>co<\/jats:italic>\u2010glycolide) microspheres were synthesized by means of complex (w\/o\/w) emulsion evaporation method. The resulting enzyme activity of the serine\u2010protease thrombin was verified by the specific chromogenic substrate S\u20102238. The thrombin release profile depended on four factors: (1) thrombin dosage, (2) polymer concentration in the o\u2010phase, (3) phase quotient w1:0 in the primary emulsion, and (4) the addition of pore\u2010introducing agents. A collagenous sponge containing thrombin\u2010loaded microspheres by means of lyophilization was developed. The impact of several production factors of the (w1\/o\/w2) solvent evaporation method to optimize thrombin encapsulation, morphology of the spheres, and desired drug release profile have been investigated. The <jats:italic>in vitro<\/jats:italic> thrombin release was dependent on the polymer\u2010to\u2010oil phase ratio, the polymer concentration, and the type of solvent and polymer. The porosity of the spheres and release rate of the active agent were enhanced by increasing the inner aqueous w1 phase. With this study, a new biodegradable hemostyptic device could be verified and established for a potentially safe and locally controlled thrombin release to manage postsurgical hemorrhage in patients undergoing anticoagulant therapy. \u00a9 2010 Wiley Periodicals, Inc. 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