Tunable Biodegradable Methacrylate Gelatin Microspheres Enable Renal Artery Embolization

Renal artery hemorrhage (RAH) is a common and potentially life-threatening medical emergency. Recent advances in interventional devices, including microguidewires and microcatheters, have made super-selective renal artery embolization (SRAE) an important treatment option for RAH because it enables precise localization of bleeding vessels, simplified procedures, reliable hemostasis, and reduced tissue injury. However, currently used embolic agents, including gelatin sponges, microcoils, polyvinyl alcohol (PVA) particles, and N-butyl cyanoacrylate (NBCA) glue, remain associated with limitations such as embolization failure, vascular injury, nontarget embolization, tissue necrosis, permanent material retention, and recurrent bleeding. In this study, we developed biodegradable gelatin methacryloyl (GelMA) microspheres as a tunable embolic agent. Two GelMA formulations with different degrees of substitution (DS), GelMA-DS0.25 and GelMA-DS0.75, were synthesized by reacting gelatin with different amounts of methacrylic anhydride. Uniform GelMA microspheres with an average diameter of 175 ± 4 μm were fabricated using microfluidics combined with photopolymerization. Under in vitro PBS conditions, GelMA-DS0.25 microspheres completely degraded in 60 days, while GelMA-DS0.75 degraded only 30% in 100 days. Incubated with 3T3 cells, the relative cell viability was over 90%, and the in vitro hemolysis rate was less than 3%, demonstrating good biocompatibility. Under digital subtraction angiography (DSA) guidance, a rabbit RAH model was established by micro-guidewire-induced vascular injury and subsequently treated by GelMA microsphere embolization. GelMA-DS0.25 microspheres showed effective embolization, initiated degradation approximately 16 days after embolization, and did not cause irreversible renal injury, as demonstrated by computed tomography (CT) follow-up and histopathological analysis. Overall, these results indicate that GelMA microspheres with uniform size, tunable degradation behavior, and favorable biocompatibility are promising biodegradable embolic candidates for super-selective renal artery embolization.