Biological evaluation and in vivo degradation steady-state endpoint exploration of a sodium alginate/poloxamer composite temperature-sensitive embolic gel for tumors.

In the regulatory science of absorbable medical devices, traditional in vivo degradation evaluations are often hindered by lengthy evaluation cycles and ambiguous standards. This restricts the research, development, and translation of novel embolic materials. The lack of an evaluation system to determine whether tissue responses have reached a "degradation steady-state endpoint" is particularly critical. This study systematically evaluated the biological efficacy and in vivo degradation steady state of a composite temperature-sensitive embolic agent based on sodium alginate and poloxamer. This gel undergoes a spontaneous phase transition at body temperature. Combined with a dual-lumen microcatheter delivery technique, it achieves instant crosslinking with calcium ions, exhibiting excellent resistance to blood flow washout. The embolization results in canine hepatic and renal artery models and rabbit renal tumor in situ models confirmed the efficacy of this composite gel as a tumor embolic agent. Its ability to induce coagulation necrosis and apoptosis in tumor tissues outperformed current clinical lipiodol and polyvinyl alcohol (PVA) microspheres. A six-month porcine hepatic/renal artery study examined residual implant-like material, recanalization, local histopathology, selected endothelial markers, and systemic observations. Under the tested protocols, the PS gel occluded target vessels and showed good biological safety. In pigs, implant-like material remained at six months, while selected histological injury and inflammatory measures were lower than at earlier terminal time points. Histopathological results indicated that local macrophage phagocytosis and inflammatory responses in the target vessels were active between 1 and 3 months. By 6 months, the inflammation level had significantly subsided to a mild state, with concurrent reductions in fibrosis and fatty infiltration. This was accompanied by prominent tissue repair and remodeling, marking a smooth transition of the tissue response toward a steady state. The results support a candidate criteria-based framework for future prospective evaluation. The results justify further formulation characterization, controlled long-term studies, and component-resolved degradation analysis.