|In Vitro and In Vivo
Evaluation of the Biocompatibility and Cytotoxicity of Local
(Department of Cardiovascular Surgery and Department
of Anesthesiology*, Tokyo Women's Medical University, Tokyo, Japan)
|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)