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To create anti-adhesive materials to be more effective and safer, we developed a thermally cross-linked gelatin film that showed superior anti-adhesive effects with excellent peritoneal regeneration. However, it may act as a convenient scaffold for tumor cell growth, thereby accelerating peritoneal dissemination when used in surgery for abdominal tumors. In this study, we tried to clarify this issue using mouse carcinomatous peritonitis models. First, we examined the in vitro tumor cell growth of mouse B16 melanoma or Colon26 cells on the gelatin film or the conventional hyarulonate/carboxymethylcellulose film. Tumor cell growth on each film was significantly lower than that of the control (no film). Next, we conducted the following in vivo experiments: After the parietal peritoneum was partially removed and covered with each film or without any film, mice were inoculated intraperitoneally with B16 melanoma or Colon26/Nluc cells expressing NanoLuc luciferase gene. At 7 days after the operation, we measured the weight of B16 melanoma tumors or the NanoLuc activity of Colon26/Nluc cells using in vivo imaging at the injured sites. There were no significant differences in the weight of the tumors and the NanoLuc activity among the three groups. We also observed the survival time of mice receiving the same operation and treatments. There was no significant difference in the survival time among the three groups. These results suggest that the gelatin film will likely not accelerate peritoneal dissemination as a convenient scaffold for tumor cell growth when used in surgery for abdominal tumors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2122-2130, 2018., (© 2017 Wiley Periodicals, Inc.)

To create more useful, effective and safer anti-adhesion materials, we developed a thermally cross-linked gelatin film. In this study, we examined the physical properties of the film such as the physical strength and the adhesiveness to reveal the handling properties and biological properties, such as the anti-adhesion effect, the influence on cell proliferation, and the cytotoxicity to reveal the anti-adhesion mechanism, especially in comparison with the conventional hyaluronic acid and carboxymethylcellulose film (the conventional film). A tensile test under dry and wet conditions and shearing stress test showed that the gelatin film has significant higher maximum tensile stress and fracture strain than the conventional film. In the study using a rat model of cecum adhesion, the anti-adhesion effect of the gelatin film was significantly superior to that of the conventional film. In the cell proliferation test, the number of fibroblast cells on the gelatin film increased at each time point, while no cell proliferation was observed on the conventional film. Furthermore, in the cytotoxicity test using a colony assay and Live/Dead assay, the extract of the gelatin film had no cytotoxicity, while the extract of the conventional film had cytotoxicity considerably. These results suggest that the gelatin film provides better handling than the conventional film, due to better physical strength and ductility of the film. In addition, the gelatin film has a significantly greater anti-adhesion effect than the conventional film without any cytotoxicity. Therefore, the gelatin film is quite favorable as an anti-adhesion material. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 689-696, 2018., (© 2017 Wiley Periodicals, Inc.)

Aim: Adhesion after pelvic surgery causes infertility, ectopic pregnancy, and ileus or abdominal pain. The materials currently available for clinical use are insufficient. The purpose of this study was to develop an anti-adhesive material that overcomes the limitations of conventional anti-adhesive agents., Methods: The adhesion prevention effects of three methods - a two-layered sheet composed of gelatin film and gelatin sponge, Seprafilm and INTERCEED - were evaluated in 37 dogs. Anti-adhesive effects were investigated macroscopically and microscopically in a cauterized uterus adhesion model. Cell growth on the materials in vitro using human peritoneal mesothelial cells, fibroblasts and uterine smooth muscle cells were also evaluated., Results: The two-layered gelatin sheet had significantly superior anti-adhesive effects compared to the conventional materials (Seprafilm and INTERCEED). A single-cell layer of mature mesothelium formed three weeks after surgery in the gelatin group. Peritoneum regeneration in the Seprafilm and INTERCEED groups was delayed and incomplete in the early phase. Little inflammation around the materials occurred and cell growth was significantly proliferated with the gelatin sheet., Conclusion: The anti-adhesive effects of a two-layered gelatin sheet were superior to conventional agents in a cauterized canine uterus model, demonstrating early regeneration of the peritoneum, little inflammation and material endurance. The newly developed two-layered gelatin sheet is a useful option as an anti-adhesive agent for deeply injured and hemorrhagic sites., (© 2017 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

In order to prevent postoperative adhesion and the related complications, a thermally crosslinked gelatin (TCG) film was developed and the basic biological properties were examined, paying special attention to the relationship between these properties and the extent of crosslinking of the film. The gelatin films crosslinked thermally for five different time periods (0, 1, 3, 8, and 14 hours) were developed and the following tests were performed. Regarding the material characterization of the films, the water content, the water solubility, and the enzymatic degradation for collagenase were found to be closely related to the duration of thermal crosslinking. In an in vitro study conducted to examine the cell growth of fibroblasts cultured on the films, the degree of cell growth, except no crosslinked film, was less than that observed in the control group, thus suggesting that such effects of the films on fibroblast cell growth may be related with their anti-adhesive effects. In in vivo tests, the films crosslinked for longer time periods (3, 8, and 14 hours) were retained for longer after being implanted into the abdominal cavity in rats and showed a significant anti-adhesive effect in the rat cecum adhesion models, indicating that the biodegradability and anti-adhesive effects of the TCG films depend on the duration of thermal crosslinking. In order to develop useful and effective anti-adhesive gelatin film, it is very important to optimize duration of the thermal crosslinking., (© 2014 Wiley Periodicals, Inc.)