Oshima Risa, Yoshihara Kumiko, Nakanishi Ko, Akasaka Tsukasa, Shimoji Shinji, Nakamura Teppei, Okihara Takumi, Nakamura Mariko, Matsukawa Akihiro, Tamada Ikkei, Van Meerbeek Bart, Sugaya Tsutomu, Yoshida Yasuhiro
Department of Periodontology, Faculty of Dental Medicine, Hokkaido University, Sapporo, Japan.
Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan.
Sci Rep. 2025 Jun 12;15(1):20056. doi: 10.1038/s41598-025-99162-x.
Bioabsorbable materials are essential for advanced therapies, including surgical sealing, cell therapy, and drug delivery. Natural bioabsorbable materials, including collagen and hyaluronic acid, have better biocompatibility than synthetic bioabsorbable polymers; however, they are mainly derived from animals, presenting infection risks. Non-animal origin polymers have a lower molecular weight than those of animal origins. Their viscosity increases with increase in molecular weight, making endotoxin removal difficult. Here, using the phosphoryl chloride disposal method, we present a strategy for synthesizing pyrogen-free bioabsorbable adhesives with controlled molecular weight. Phosphopullulan, a polysaccharide derivative, had less than detectable endotoxin levels and controllable average molecular weight of approximately 300,000 to over 1,400,000. Furthermore, it is important to ensure the safety as well as efficacy of bio-implantable materials. We have evaluated the biosafety of polysaccharide derivatives we are developing, and have examined their cell phagocytosis and pharmacokinetics in vitro and in vivo, and have confirmed that they are safe. We have also evaluated their adhesion to wet tissue adhesions and confirmed that they leak less than existing materials.
生物可吸收材料对于包括手术密封、细胞治疗和药物递送在内的先进疗法至关重要。天然生物可吸收材料，包括胶原蛋白和透明质酸，比合成生物可吸收聚合物具有更好的生物相容性；然而，它们主要来自动物，存在感染风险。非动物源聚合物的分子量低于动物源聚合物。它们的粘度随分子量增加而增加，使得内毒素去除困难。在此，我们使用氯化磷处理方法，提出了一种合成具有可控分子量的无热原生物可吸收粘合剂的策略。磷酸普鲁兰多糖，一种多糖衍生物，内毒素水平低于可检测限，平均分子量可控，约为300,000至超过1,400,00。此外，确保生物可植入材料的安全性和有效性很重要。我们评估了正在开发的多糖衍生物的生物安全性，并在体外和体内检查了它们的细胞吞噬作用和药代动力学，证实它们是安全的。我们还评估了它们对湿组织粘连的粘附性，并证实它们的渗漏比现有材料少。
