Biodegradable Polydioxanone Microspheres for Transcatheter Arterial Embolization: Proof of Principle.

PURPOSE: To evaluate feasibility, embolization success, biodegradability, reperfusion, and biocompatibility of biodegradable microspheres (MS) made from polydioxanone (PDO) for transcatheter arterial embolization. MATERIALS AND METHODS: Unilateral selective renal embolization of a segmental artery was performed in 16 New Zealand White rabbits with PDO-MS (100-150 µm and 90-315 µm). Animals were randomly assigned to different observation periods and underwent control digital subtraction angiography (DSA) and MR imaging immediately (n = 3), 1 week (n = 2), 4 weeks (n = 2), 8 weeks (n = 2), 12 weeks (n = 5), and 16 weeks (n = 2) after embolization. Kidneys were harvested for macroscopic and histologic analysis of embolization success, biodegradability, and biocompatibility. RESULTS: Embolization was technically successful in 15 of 16 animals. One animal died of anesthesia-related circulatory failure. The 100-150 µm MS were injected easily through 3-F catheters; the 90-315 µm MS tended to clog with intermittent catheter obstruction. DSA and MR imaging showed successful target embolization in 13 of 15 animals. In 2 animals, the entire kidney was affected owing to catheter clogging, including a reflux of MS while flushing. Control DSA and MR imaging showed increasing vascular reperfusion with time. Macroscopic and histologic analysis revealed necrosis/infarction in areas in which embolization was achieved. MS were extensively degraded after 16 weeks, and overall inflammatory reaction was mild. CONCLUSIONS: Biodegradable PDO-MS induced effective embolization of target vessels while demonstrating good biocompatibility. MS increasingly dissolved at 16 weeks, partial reperfusion started at week 1, and complete reperfusion started at week 8, thus offering possible advantages as a temporary embolic agent.

Novel MR-Visible, Biodegradable Microspheres for Transcatheter Arterial Embolization: Experimental Study in a Rabbit Renal Model.

PURPOSE: To assess feasibility, embolization success, biodegradability, reperfusion, biocompatibility and in vivo visibility of novel temporary microspheres (MS) for transcatheter arterial embolization. MATERIAL AND METHODS: In 9 New Zealand white rabbits unilateral superselective embolization of the lower kidney pole was performed with biodegradable MS made of polydioxanone (PDO) (size range 90-300 and 200-500 µm) impregnated with super-paramagnetic iron oxide (SPIO). Magnetic resonance imaging (MRI) was performed post-interventionally to assess in vivo visibility. Embolization success was assessed on digital subtraction angiography, MRI and gross pathology. One animal was killed immediately after embolization to assess original particle appearance. 8 animals were randomly assigned to different observation periods (1, 4, 8, 12 and 16 weeks), after which control angiography and MRI were obtained to determine recanalization. Histopathological analysis was performed to determine biodegradability and biocompatibility by using dedicated quantitative assessment analysis. RESULTS: Ease of injection was moderate. Embolization was technically successful in 7 of 8 animals, one rabbit received non-selective embolization of the whole kidney and abdominal off-target embolization. Arterial occlusion was achieved in all kidneys, infarct areas in macro- and microscopic analysis confirmed embolization success. Control angiograms showed evidence of partial reperfusion. The microspheres showed extensive degradation over the course of time along with increasing inflammatory response and giant cell formation. SPIO-loaded MS were visible on MRI at all time points. CONCLUSIONS: SPIO-impregnated biodegradable PDO-MS achieved effective embolization with in vivo visibility on MRI and increasing biodegradation over time while demonstrating good biocompatibility, i.e., a physiologically immune response without transformation into chronic inflammation. Further studies are needed to provide clinical applicability.

Genotyping-By-Sequencing (GBS) Detects Genetic Structure and Confirms Behavioral QTL in Tame and Aggressive Foxes (Vulpes vulpes).

The silver fox (Vulpes vulpes) offers a novel model for studying the genetics of social behavior and animal domestication. Selection of foxes, separately, for tame and for aggressive behavior has yielded two strains with markedly different, genetically determined, behavioral phenotypes. Tame strain foxes are eager to establish human contact while foxes from the aggressive strain are aggressive and difficult to handle. These strains have been maintained as separate outbred lines for over 40 generations but their genetic structure has not been previously investigated. We applied a genotyping-by-sequencing (GBS) approach to provide insights into the genetic composition of these fox populations. Sequence analysis of EcoT22I genomic libraries of tame and aggressive foxes identified 48,294 high quality SNPs. Population structure analysis revealed genetic divergence between the two strains and more diversity in the aggressive strain than in the tame one. Significant differences in allele frequency between the strains were identified for 68 SNPs. Three of these SNPs were located on fox chromosome 14 within an interval of a previously identified behavioral QTL, further supporting the importance of this region for behavior. The GBS SNP data confirmed that significant genetic diversity has been preserved in both fox populations despite many years of selective breeding. Analysis of SNP allele frequencies in the two populations identified several regions of genetic divergence between the tame and aggressive foxes, some of which may represent targets of selection for behavior. The GBS protocol used in this study significantly expanded genomic resources for the fox, and can be adapted for SNP discovery and genotyping in other canid species.