Narita Takefumi, Yunoki Shunji, Ohyabu Yoshimi, Yahagi Naohisa, Uraoka Toshio
Biotechnology Group, Tokyo Metropolitan Industrial Technology Research Institute, Koto-ku.
Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Shinjuku-ku.
Med Devices (Auckl). 2016 Dec 15;9:429-439. doi: 10.2147/MDER.S116633. eCollection 2016.
We investigated the potential of collagen-genipin sols as biomaterials for treating artificial ulcers following endoscopic submucosal dissection. Collagen sol viscosity increased with condensation, allowing retention on tilted ulcers before gelation and resulting in collagen gel deposition on whole ulcers. The 1.44% collagen sols containing genipin as a crosslinker retained sol fluidity at 23°C for >20 min, facilitating endoscopic use. Collagen sols formed gel depositions on artificial ulcers in response to body temperature, and high temperature responsiveness of gelation because of increased neutral phosphate buffer concentration allowed for thick gel deposition on tilted ulcers. Finally, histological observations showed infiltration of gels into submucosal layers. Taken together, the present data show that genipin-induced crosslinking significantly improves the mechanical properties of collagen gels even at low genipin concentrations of 0.2-1 mM, warranting the use of in situ gelling collagen-genipin sols for endoscopic treatments of gastrointestinal ulcers.
我们研究了胶原-京尼平溶胶作为内镜下黏膜下剥离术后治疗人工溃疡生物材料的潜力。胶原溶胶的粘度随着缩合而增加，使其在凝胶化前能保留在倾斜的溃疡面上，并导致胶原凝胶沉积在整个溃疡面上。含有京尼平作为交联剂的1.44%胶原溶胶在23°C下保持溶胶流动性超过20分钟，便于内镜使用。胶原溶胶在体温作用下在人工溃疡上形成凝胶沉积物，由于中性磷酸盐缓冲液浓度增加导致的凝胶化高温响应性使得在倾斜溃疡面上形成厚凝胶沉积物。最后，组织学观察显示凝胶渗入黏膜下层。综上所述，目前的数据表明，即使在0.2-1 mM的低京尼平浓度下，京尼平诱导的交联也能显著改善胶原凝胶的机械性能，这使得原位凝胶化的胶原-京尼平溶胶可用于胃肠道溃疡的内镜治疗。
