Calibrated Bioresorbable Microspheres as an Embolic Agent: An Experimental Study in a Rabbit Renal Model

Abstract

Purpose To evaluate the time frame of resorption and tissue response of newly developed bioresorbable microspheres (BRMS) and vessel recanalization after renal embolization. Materials and Methods Embolization of lower poles of kidneys of 20 adult rabbits was performed with BRMS (300–500 μm). Two rabbits were sacrificed immediately after embolization (day 0). Three rabbits were sacrificed after follow-up angiography at 3, 7, 10, 14, 21, and 30 days. The pathologic changes in the renal parenchyma, BRMS degradation, and vessel recanalization were evaluated histologically and angiographically. Results Embolization procedures were successfully performed, and all animals survived without complication. Infarcts were observed in all kidneys that received embolization harvested after day 0. Moderate degradation of BRMS (score = 1.07 ± 0.06) was observed by day 3. Of BRMS, 95% were resorbed before day 10 with scant BRMS materials remaining in the arteries at later time points. Partial vessel recanalization was observed by angiography starting on day 3, whereas new capillary formation was first identified histologically on day 7. Vascular inflammation associated with BRMS consisted of acute, heterophilic infiltrate at earlier time points (day 3 to day 10); this was resolved with the resorption of BRMS. Inflammation and fibrosis within infarcted regions were consistent with progression of infarction. Conclusions BRMS were bioresorbable in vivo, and most BRMS were resorbed before day 10 with a mild tissue reaction. Vessel recanalization occurred secondary to the resorption of BRMS.

Polymeric materials for embolic and chemoembolic applications

“…The hydrolyzable starch has a short half-life, minute scale, and the particles have very small diameters, averaging 50 μm, limiting clinical applications. The advancement of degradable embolics has been slower, but several labs are currently developing improved materials [49,110,111]. Treatment of uterine fibroids, for example, requires transient embolization of the uterine artery, particularly in patients who want to remain fertile.…”

“…Inflammatory cell infiltration was observed at all time points, and sometimes microspheres were found encapsulated within a thrombus but at different stages of degradation and phagocytosis. A more comprehensive animal study was later conducted and rabbits were sacrificed at additional points to sufficiently profile in vivo degradation and resultant inflammatory response [110]. Resorbable MSs, size range 300–500 μm, of oxidation degree 25% were used in these studies (in between OC-II and OC-III).…”

Advances in Degradable Embolic Microspheres: A State of the Art Review

“…It may also be possible these spaces resulted from thrombus formation, as the authors noted “visible tissue and blood cells that surrounded the microspheres were erased” prior to analysis [ 42 ]. Although risk assessment was limited in this paper due to its short timeframe, the authors have published a subsequent study, which is considerably more focused on the special controls published by FDA; this follow-up study was not included in the present review as it did not meet the inclusion criteria (lack of commercial control), but is cited so as to direct the readers toward additional data for these materials [ 44 ].…”

Drug-eluting embolic microspheres for local drug delivery – State of the art

“…Most recently developed drug-loaded microspheres were also designed to be biodegradable (or resorbable) and compressible ( [19,[78][79][80]. The rate of degradation may be modulated by polymer crosslinking density and drug loading, ranging from less than 10 days for unloaded microspheres in vivo, to 3 months for doxorubicin-eluting microspheres in vitro [78,80]. showed the most sustained release for sunitinib among the three drugs, with 48-62% of sunitinib released at 6 hours and complete release after 24 hours [84,85].…”