精准血液净化介入治疗吸附材料的构建、制备与功能调控

血液透析是肾衰竭患者的生命支持系统，目前因尚缺乏持续有效的甲状旁腺激素（PTH）去除技术，肾衰竭患者面临严重的透析并发症，致残致死率高。针对这一问题，本项目首次提出以抗PTH纳米抗体为功能基研制介入吸附材料实现连续精准血液净化的解决思路。该思路采用留置针静脉插管，利用类笔芯式可更换介入材料实现PTH类痕量毒素的持续有效去除。针对这一思路，提出制备微米梁骨架纳米抗体冰胶整体介入材料的创新技术和方法。其优势在于: 利用不锈钢丝簇微米梁骨架可以显著增强介入材料力学性能；冰胶材料的大孔径、贯通孔特性不仅有效解决了介入材料吸附表面积低的难题，同时具有良好的吸附动力学特性；以定点修饰聚合基团的纳米抗体为单体，发展冰晶微液相浓缩表面聚合技术“一锅法”制备冰胶，能够实现纳米抗体的高密度高活性固载，将显著提升介入材料的吸附容量和血液相容性。本项目研究成果将为痕量毒素便携式血液净化器件研发奠定理论和技术基础。

Hemodialysis serves as a life-support system for the patients with renal failure. The lack of continuously effective tools for the removal of middle molecules such as parathyroid hormone (PTH) has forced the renal failure patients to confront with severe dialysis complications, high disability rate and frequent fatality. To preform long-term precise hemopurification, we propose a novel interventional adsorption system based on anti-Hemodialysis serves as a life-support system for the patients with renal failure. The lack of continuously effective tools for the removal of middle molecules such as parathyroid hormone (PTH) has forced the renal failure patients to confront with severe dialysis complications, high disability rate and frequent fatality. To preform long-term precise hemopurification, we propose a novel interventional adsorption system based on anti-PTH nanobodies. Aiming at developing replaceable functional inserts in venous indwelling needle for the removal of PTH and PTH-like trace toxins, we introduce microfiber reinforced macroporous cyrogel-monolith. This novel system features the following designs: First, stainless steel clusters embedded in the macroporous cyrogel-monolith enhance the mechanical properties of the interventional material. Then, cryogel consists of large-aperture thru holes greatly improves surface area and adsorption dynamics as compared with the traditional interventional material with undesirable low surface area. Meanwhile, the one-pot preparation of cryogel by surface polymerization in unfrozen liquid microphase using site-directed alkene modified nanobodies as monomers ensures the dense and active immobilization of nanobodies, leading to superior adsorption capacity and hemocompatibility of interventional material. In summary, our research provides valuable information that builds a solid foundation for both theory and techniques in the development of portable hemolysis devices for the removal of trace toxins in blood.