3D打印USPIO/EGCG功能化双层水凝胶胆道支架的构建及体外功能评价OA

Background and Aims:Biliary stricture remains challenging to treat because of limitations related to stent mechanical performance,restenosis,and postoperative monitoring.This study aimed to develop a 3D-printed ultrasmall superparamagnetic iron oxide(USPIO)/epigallocatechin gallate(EGCG)functionalized bilayer hydrogel biliary stent integrating mechanical support,local drug delivery,and MRI visibility,and to evaluate its physicochemical and in vitro biological properties. Methods:Polycaprolactone methacrylate(PCLMA)was used to construct the mechanically supportive inner layer,while gelatin methacryloyl(GelMA)was used as the bioactive outer layer.Mesoporous silica nanoparticles(MSN)loaded with EGCG and USPIO were incorporated into the hydrogel system.A PCLMA/GelMA/MSN@USPIO@EGCG bilayer hydrogel biliary stent was fabricated by 3D printing and photocrosslinking.The structural and physicochemical properties of the materials were characterized using transmission electron microscopy,scanning electron microscopy,Fourier-transform infrared spectroscopy,proton nuclear magnetic resonance spectroscopy,dynamic light scattering,and rheological analysis.In vitro degradation and EGCG release were evaluated,and MRI was used to assess the imaging capability conferred by USPIO.The cytocompatibility,cell proliferation,reactive oxygen species(ROS),mitochondrial membrane potential,and cellular senescence of human adipose-derived mesenchymal stem cells(hADSC)were evaluated.Hemolysis and coagulation assays were performed to assess hemocompatibility. Results:The prepared MSN and composite nanoparticles exhibited relatively uniform spherical morphology and good dispersion,while the PCLMA/GelMA/MSN@USPIO@EGCG stent showed a regular porous grid-like structure.The PCLMA inner layer exhibited high compressive strength,whereas the GelMA-based composite hydrogel showed favorable viscoelastic properties.The composite stent exhibited controllable degradation and sustained EGCG release in vitro.USPIO incorporation conferred a distinct T2-weighted negative MRI contrast effect,with a strong linear relationship between the relaxation rate and iron concentration.All stent groups showed good cytocompatibility and supported hADSCs adhesion and spreading.EGCG incorporation further enhanced cell proliferation,reduced oxidative stress,and helped maintain mitochondrial membrane potential.The composite stent caused no obvious hemolytic or coagulation abnormalities over the tested concentration and incubation ranges. Conclusion:A 3D-printed bilayer hydrogel biliary stent with mechanical support,sustained EGCG release,and MRI visibility was successfully developed.The stent exhibited favorable biodegradability,cytocompatibility,and cytoprotective properties in vitro,providing a potential biomaterial strategy for local microenvironment modulation and imaging-assisted monitoring of biliary strictures.Its in vivo safety and anti-restenotic efficacy require further investigation.