Intrinsically disordered protein condensate-based coating on ureteral stents for anti-fouling and anti-encrustation

Ureteral stents are among the most frequently used devices in urology, yet their high susceptibility to biofilm and encrustation continues to evade current surface-coating strategies. The development of emerging coatings faces significant challenges due to the complex physiological environment of the urinary tract, featuring high salinity, continuous shear stress, fluctuating pH, and microbial contamination. Here, we report an effective anti-fouling and anti-encrustation surface-engineering strategy by developing a coating from intrinsically disordered protein condensates of fused in sarcoma (FUS) protein (IDP_FUS) and applying it to ureteral stents via a polydopamine-assisted two-step modified method. The IDP_FUS-modified surface exhibited markedly enhanced hydrophilicity and demonstrated strong resistance to nonspecific protein adsorption, urinary tract infection-related bacteria adhesion, and ureteral epithelial cell attachment, significantly outperforming the benchmark polyethylene glycol (PEG) coating. In a rat model of infection-induced urolithiasis, the IDP_FUS coating reduced stent encrustation by over 80% compared to clinical polyurethane and Percuflex™ stents, and markedly mitigated local tissue inflammation. Mechanistically, IDP_FUS is thought to form a hydrating, densely entangled network through coacervation, which can help minimize surface contamination. This dynamic network could also inhibit stone nucleation near the stent surfaces by regulating local pH and ionic strength through charge neutralization and non-ionic interactions. These findings address the long-standing challenge of biofilm and encrustation on urinary implants by leveraging the integrated capabilities of IDP_FUS condensate, including strong hydration, fouling resistance, and dynamic buffering, highlighting its translational potential for use in complex biofluids. STATEMENT OF SIGNIFICANCE: Ureteral stent encrustation remains a major clinical problem that is inadequately addressed by current hydrophilic coatings in the challenging urinary environment. This work introduces a bioinspired anti-encrustation coating made from intrinsically disordered proteins that forms highly hydrated, tightly tangled networks. Unlike conventional materials, this protein-based layer can spontaneously coacervate and locally regulate pH and ionic strength, preventing the initial attachment of proteins, bacteria and cells, while reducing stone formation. By demonstrating over 80% reduction of infection-induced encrustation compared with clinical stents, this study establishes intrinsically disordered proteins as a promising class of functional biomaterials with broad potential for improving urinary implants and other medical devices exposed to harsh biological environments.