Long-Term Implantability of Resorbable Carboxymethyl Cellulose/Chitosan Microspheres in a Rabbit Renal Arterial Embolization Model.

Abstract

To determine the physiologic response to resorbable carboxymethyl cellulose/chitosan (CMC/CN) microspheres in a long-term rabbit model, including the clinical response, gross pathology, and histopathology. Six rabbits were embolized with CMC/CN microspheres (300-500µm) in one kidney via an inferior renal artery branch. Angiography was performed immediately before and after embolization and prior to killing at 6months (180 ± 7days, n = 3) and 12months (365 ± 10days, n = 3). A complete necropsy was performed on each animal with dissection of the kidneys and harvesting of additional tissues as per ISO-10993-part 6 and ISO-10993-part 11 guidelines. All tissues were processed and stained for pathological analysis. The caudal third of target kidneys was successfully embolized with CMC/CN microspheres. Over the course of the study, there were neither notable clinical signs in either embolization group nor significant changes in the tissue/body weight ratio between 6- and 12-month time points. Gross examination revealed that all embolized kidneys had morphologic features consistent with infarction resulted from microsphere delivery. The percentage of infarction decreased from 9.1% ± 5.7% at 6months to 1.9% ± 0.4% at 12months. Microscopically, infarcted areas demonstrated evidence of chronic injury and repair, including loss of renal parenchyma with replacement fibrosis, tubular regeneration, and minimal to mild lymphoplasmacytic inflammation without any active changes such as necrosis or neutrophilic inflammation. No systemic toxicity was observed in the animals 6 and 12months after CMC/CN microspheres delivery. The local tissue response was mild.