目的

输尿管支架作为泌尿外科关键植入器械，在临床应用过程中长期面临术后疼痛、生物污染、表面结壳等并发症挑战。传统表面改性技术受限于材料表面性质，存在涂层稳定性差、制备工艺复杂等瓶颈。本研究基于聚多巴胺（PDA）的普适性粘附机制与FUS蛋白固有无序区（IDP）的界面调控特性，开发新型仿生复合涂层体系，旨在通过分子设计实现输尿管支架表面功能化，提升其抗污染、抗结壳及生物相容性性能，为降低支架相关并发症提供创新解决方案。

方法

1.涂层构建：采用两步法在聚氨酯支架表面构建功能涂层。首先利用多巴胺在碱性条件下通过氧化自聚形成聚多巴胺中间层；随后利用PDA涂层独特的粘附机制，将重组IDPFUS蛋白固载于PDA涂层表面，形成PDA-IDPFUS蛋白涂层。

2.性能表征：采用扫描电镜（SEM）与分析涂层形貌及粗糙度；使用能量色散X射线光谱仪（EDS）验证化学元素组成；通过水接触角测试评估涂层亲水性。

3.功能验证：通过动态监测支架表面亲水性随时间变化情况验证涂层稳定性；以大肠杆菌为模型菌，通过菌落平板计数法评价涂层抗细菌粘附效果；建立大鼠输尿管支架植入模型，评估支架留置14天后的表面结壳程度；动物试验结束后通过组织病理学评估支架组织相容性。

结果

1.理化特性：与未处理的支架相比，IDPFUS蛋白涂层修饰的支架表面平整度有所改善，EDS分析其表面元素分布显示其表面S元素含量明显上升，表明IDPFUS蛋白涂层成功接枝在输尿管支架表面。并且水接触角测试结果显示PDA-IDPFUS涂层修饰支架表面水接触角降至37.1±4.5°，较未修饰支架（113.6±3.0°）亲水性提升67.3%。

2.功能表现：抗菌实验中，PDA-IDPFUS涂层表现出明显的抗细菌粘附的效果；在大鼠实验中，PDA-IDPFUS涂层支架表面结壳质量仅为26.70±27.3mg，较其他各组明显降低；术后病理学分析表明PDA-IDPFUS涂层表现出最优生物相容性，组织切片中仅见轻度炎症，中性粒细胞数量显著减少，且黏膜结构完整，无纤维化或水肿病变。

结论

本研究成功构建了基于PDA-IDPFUS的功能涂层体系，在体外和动物实验中，证明了构建的IDPFUS蛋白涂层具有优异的亲水性、稳定性、生物相容性和防污性能，能够有效提升支架表面润滑度、抑制细菌污染以及防止支架表面结壳。为解决输尿管支架相关并发症，以及长期留置输尿管支架的开发提供了创新解决方案。

Objective

Ureteral stents, as key implantable devices in urology, have long faced the challenges of complications such as biological contamination, crusting and tissue irritation during clinical application. Traditional surface modification techniques are limited by the surface properties of the materials, and there are bottlenecks such as poor coating stability and complicated preparation processes. In this study, we developed a novel biomimetic composite coating system based on the pervasive adhesion mechanism of polydopamine (PDA) and the interfacial regulation properties of the intrinsic disordered region (IDP) of FUS protein, aiming to functionalize the surface of ureteral stents through molecular design, enhance their anti-contamination, anti-crusting and biocompatibility properties, and provide innovative solutions to reduce stent-related complications.

Methods

1. Coating construction: a two-step method was used to construct a functional coating on the surface of polyurethane stents. First, a polydopamine intermediate layer was formed by oxidative self-polymerization of dopamine under alkaline conditions; subsequently, recombinant IDPFUS protein was cemented onto the surface of the PDA coating using the unique adhesion mechanism of PDA coating to form a PDA-IDPFUS protein coating.

2. Performance characterization: Scanning electron microscopy (SEM) was used to analyze the morphology and roughness of the coating; energy dispersive X-ray spectrometry (EDS) was used to verify the composition of the chemical elements; and the hydrophilicity of the coating was evaluated by water contact angle test.

3. Functional verification: The stability of the coating was verified by dynamically monitoring the change of hydrophilicity of the stent surface over time; the anti-bacterial adhesion effect of the coating was evaluated by colony plate counting using Escherichia coli as a model bacterium; the implantation model of ureteral stent in rats was established to evaluate the degree of surface crusting of the stent after leaving it in the stent for 14 days; and the stent's tissue compatibility was evaluated by histopathology at the end of the animal test.

Results

1. Physicochemical properties: Compared with the untreated stent, the surface flatness of the IDPFUS protein-coated modified stent was improved, and the EDS analysis of its surface element distribution showed a significant increase in the surface S element content, indicating that the IDPFUS protein coating was successfully grafted on the surface of the ureteral stent. Moreover, the water contact angle test results showed that the water contact angle of the PDA-IDPFUS coated modified stent surface was reduced to 37.1°±4.5°, which increased the hydrophilicity by 67.3% compared with that of the unmodified stent (113.6°±3.0°).

2. Functional performance: In the antibacterial experiment, PDA-IDPFUS coating showed obvious anti-bacterial adhesion effect; in the rat experiment, the surface crust mass of PDA-IDPFUS coated scaffolds was only 26.70±27.3 mg, which was significantly lower than that of the other groups; postoperative pathology analysis showed that the PDA-IDPFUS coating showed optimal biocompatibility, and only mild inflammation and neutrophilia were seen in the tissue sections. Mild inflammation was seen in the tissue sections, the number of neutrophils was significantly reduced, and the mucosal structure was intact without fibrosis or edema lesions.

Conclusion

In this study, a functional coating system based on PDA-IDPFUS was successfully constructed, and in vitro and animal experiments, it was demonstrated that the constructed IDPFUS protein coating had excellent hydrophilicity, stability, biocompatibility, and antifouling properties, and was able to effectively improve the lubricity of the scaffold surface, inhibit the bacterial contamination, and prevent the scaffold surface from crusting. This provides an innovative solution to address the complications associated with ureteral stents and the development of long-term indwelling ureteral stents.