In Vitro and In Vivo Evaluation of the Biocompatibility and Cytotoxicity of Local Hemostatic Agents

(Department of Cardiovascular Surgery and Department of Anesthesiology*, Tokyo Women's Medical University, Tokyo, Japan)

Yasuko Tomizawa Makiko Komori* Katsumi Takada*
Hiroshi Nishida Masahiro Endo Hiromi Kurosawa
When local hemostatic agents are used in surgery, rapid dissolution followed by prompt absorption without adverse effect after successful hemostasis are essential qualities. Residual hemostatic materials greatly influence host cells during the wound healing process. Biocompatibility of material is also essential. Furthermore, hemostatic agents also should be free of cytotoxicity that may block mitosis and migration of host cells, so that wound healing can proceed smoothly. For the evaluation of biocompatibility and cytotoxicity, 4 commercially available hemostatic agents; oxidized regenerated cellulose (Surgicel¨), gelatin sponge (Spongel¨), microfibrillar collagen (Avitene¨) and cotton type collagen (Integran¨) were tested in vitro and in vivo. The hydrogen ion concentration (pH) of culture medium containing hemostatic agents was measured. Fibroblasts were cultured with the hemostatic agents in petri dishes for 5 days. A rabbit ear chamber (REC) model was used to evaluate tissue compatibility and the healing process. Each hemostatic agent was placed in the REC and evaluated macroscopically once a week up to 5 weeks. At 72 h, the pH of the culture medium containing Surgicel was low at 7.2, while they stayed between 7.7-7.8 with the other agents. In the fibroblast culture containing Surgicel, cell detachment occurred and the cell numbers decreased, while no particular changes occurred with other hemostatic agents. In the REC model, after 5 weeks Surgicel was dissolved and remained in the effusion, and the healing process was disturbed by inflammation. Spongel was dissolved and absorbed, with normal vasculature. Avitene was dissolved and remained in the effusion, but did not induce strong inflammation. With Integran, the healing process was prompt but the material was still recognizable at 5 weeks. The 4 hemostatic materials tested showed differences in biocompatibility and cytotoxicity. The ability of hemostasis is important; however, after hemostasis is achieved, unused hemostatic material should be eliminated, leaving as little hemostatic agent as possible to avoid postoperative complications.
@Jpn. J. Cardiovasc. Surg. 33: 382-386 (2004)