Characteristics and efficacy of fish-derived gelatin microparticles as an embolic agent in a rabbit renal model: regulation of the degradation period by molecular weight.

Abstract

To evaluate the embolic effect of fish-derived gelatin microparticles (GMPs) and compare the degradation periods and biocompatibilities of different molecular weight (MW) GMPs in a rabbit model. GMPs were designed to degrade within 21 days (high MW GMP, 15-30 kDa) and 2 days (low MW GMP, 5-15 kDa) in vivo. Renal arteries of 24 rabbits were embolized using both high and low MW GMPs (155-350 µm). Rabbits were sacrificed either immediately after embolization, or after follow-up (F/U) angiogram on days 2 and 21 of embolization, respectively (4 rabbits in each of the 6 subgroups). Pathological changes of recanalized vessels were evaluated using the Banff classification. For the in vitro study, each type of GMP was mixed with normal saline and morphological changes were compared for 14 days. Fish-derived GMPs showed effective embolization. On 2-day F/U angiography, occluded vessels were more recanalized to the peripheral branches in low MW group. On day 21, a parenchymal perfusion defect recovered to a greater extent in low MW group than that in high MW group. Mean Banff scores for intimal arteritis on 2-day F/U and interstitial fibrosis on 21-day F/U were higher in high MW group (1.75 ± 0.58 vs. 0.19 ± 0.4 and 2.56 ± 0.63 vs. 0.88 ± 0.89; P < .001). On in vitro assessment, low MW GMP lost the spherical shape and degraded, and was invisible on microscopy on day 6, whereas high MW GMP was only partially degraded after 2 weeks. Fish-derived GMPs showed effective embolization in a rabbit model. Low MW GMPs degraded within 2 days with a low inflammatory response.