Search

Background and study aims: Recently, the shielding method with polyglycolic acid (PGA) fabric and fibrin glue (P-F method) has been reported to prevent serious complications after endoscopic submucosal dissection (ESD). However, the effectiveness and mechanism to prevent complications by this method remain unclear and the corresponding basic research has not been fully conducted. Methods and results: We examined the effectiveness and mechanism of the P-F method, using a surgical ESD model of canine stomach and in vitro experiments. In the model experiment treated by P-F method or no treatment (control), ulcer perforation or penetration occurred only in the control group, but not in the P-F group. Microscopically, the P-F group showed less damages of the ulcer lesion than that of the control group, showing thicker granulation tissues including PGA fibers on the third day and excellent mucosal regeneration on the fourteenth day. In vitro culture experiments showed that fibroblasts proliferated at a significantly higher rate on PGA than on fibrin or a complex thereof. However, under hydrochloric acid treatment, fibroblasts were protected by fibrin, followed by the complex of both, and PGA. Conclusion: The P-F method exhibited a protective effect against gastric juice by fibrin glue to reduce tissue damages and a scaffold function of PGA fabric to induce better granulation formation at the earlier phase, resulting in excellent long-term tissue repair, on ulcer lesion following ESD, although the results were based on basic experiments.

Abstract: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. J Biomed Mater Res Part B: Appl Biomater, 103B: 1511-1518, 2015. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a worldwide pandemic. Early data suggest that the prevalence and severity of COVID-19 appear to be higher among patients with underlying cardiovascular risk factors. Despite the expression of angiotensin-converting enzyme 2 (ACE2), a functional receptor for SARS-CoV-2 infection, in cardiomyocytes, there has been no conclusive evidence of direct viral infection although the presence of inflammation and viral genome within the hearts of COVID-19 patients have been reported. Here we transduced A549 lung epithelial cells with lentivirus overexpressing selected genes of the SARS-CoV-2. We then isolated extracellular vesicles (EVs) from the supernatant of A549 cells and detected the presence of viral RNA within the purified EVs. Importantly, we observed that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were able to actively uptake these EVs and viral genes were subsequently detected in the cardiomyocytes. Accordingly, uptake of EVs containing viral genes led to an upregulation of inflammation-related genes in hiPSC-CMs. Thus, our findings indicate that SARS-CoV-2 RNA-containing EVs represent an indirect route of viral RNA entry into cardiomyocytes.