Chen Hong, Wu Pan, Xu Hong, Wang Changchun
Children's Hospital of Fudan University, Shanghai, China.
State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, and Laboratory of Advanced Materials, Fudan University, Shanghai, China.
Front Bioeng Biotechnol. 2021 Oct 7;9:746609. doi: 10.3389/fbioe.2021.746609. eCollection 2021.
Vesicoureteral reflux (VUR) is one of the most common congenital anomalies in the kidney and the urinary tract. Endoscopic subureteral injection of a bulking agent has become popular in VUR treatment due to its high success rates, few complications, and a straightforward procedure. In this study, a novel magnetic bulking agent was prepared by embedding FeO magnetic nanoparticles in cross-linked agarose microspheres with diameters of 80-250 μm and dispersing the magnetic microspheres in a hyaluronic acid hydrogel. The bulking agent has good biocompatibility and biosecurity validated by the tests of cytotoxicity, genotoxicity, animal irritation, skin sensitization, acute systemic toxicity, and pathological analysis after the injection of the bulking agent extract solution into healthy mice as well as injection of the bulking agent into VUR rabbits. The VUR rabbits were created by incising the roof of the intravesical ureter to enlarge the ureteral orifice. The success rate of the bulking agent in treating VUR rabbits using a subureteral transurethral injection technique was 67% (4/6) or 80% (4/5, excluding the unfinished rabbit), and no migrated particles were found in the organs of the rabbits. The transverse relaxation rate of the bulking agent was 104 mMs. After injection, the bulking agent was long-term trackable through magnetic resonance imaging that can help clinicians to inspect the VUR treatment effect. For the first time, this study demonstrates that the bulking agent with a long-term stable tracer is promising for endoscopic VUR treatment.
膀胱输尿管反流（VUR）是肾脏和尿路最常见的先天性异常之一。内镜下输尿管下注射填充剂因其成功率高、并发症少且操作简单，在VUR治疗中已变得流行。在本研究中，通过将FeO磁性纳米颗粒嵌入直径为80 - 250μm的交联琼脂糖微球中，并将磁性微球分散在透明质酸水凝胶中，制备了一种新型磁性填充剂。通过细胞毒性、遗传毒性、动物刺激性、皮肤致敏性、急性全身毒性测试以及将填充剂提取液注射到健康小鼠体内和将填充剂注射到VUR兔体内后的病理分析，验证了该填充剂具有良好的生物相容性和生物安全性。VUR兔通过切开膀胱内输尿管顶部以扩大输尿管口来创建。使用输尿管下经尿道注射技术，填充剂治疗VUR兔的成功率为67%（4/6）或80%（4/5，不包括未完成的兔子），且在兔子器官中未发现迁移颗粒。填充剂的横向弛豫率为104 mM/s。注射后，可通过磁共振成像对填充剂进行长期追踪，这有助于临床医生检查VUR治疗效果。本研究首次表明，具有长期稳定示踪剂的填充剂在内镜下VUR治疗中具有前景。
