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

Lihui Weng, Davis Seelig, Omid Souresrafil

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: 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. Materials and Methods: Six rabbits were embolized with CMC/CN microspheres (300–500 µm) in one kidney via an inferior renal artery branch. Angiography was performed immediately before and after embolization and prior to killing at 6 months (180 ± 7 days, n = 3) and 12 months (365 ± 10 days, 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. Results: 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 6 months to 1.9% ± 0.4% at 12 months. 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. Conclusion: No systemic toxicity was observed in the animals 6 and 12 months after CMC/CN microspheres delivery. The local tissue response was mild.

Original languageEnglish (US)
Pages (from-to)951-958
Number of pages8
JournalCardioVascular and Interventional Radiology
Volume41
Issue number6
DOIs
StatePublished - Jun 1 2018

Fingerprint

Carboxymethylcellulose Sodium
Microspheres
Rabbits
Kidney
Infarction
Tissue and Organ Harvesting
Inflammation
Renal Artery
Dissection
Regeneration
Angiography
Fibrosis
Necrosis
Body Weight
carboxymethyl-chitosan
Guidelines
Pathology
Wounds and Injuries

Keywords

  • Arterial embolization
  • Bioresorbable microspheres
  • Implantability
  • Local effect
  • Systemic toxicity

PubMed: MeSH publication types

  • Journal Article

Cite this

Long-Term Implantability of Resorbable Carboxymethyl Cellulose/Chitosan Microspheres in a Rabbit Renal Arterial Embolization Model. / Weng, Lihui; Seelig, Davis; Souresrafil, Omid.

In: CardioVascular and Interventional Radiology, Vol. 41, No. 6, 01.06.2018, p. 951-958.

Research output: Contribution to journalArticle

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abstract = "Purpose: 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. Materials and Methods: Six rabbits were embolized with CMC/CN microspheres (300–500 µm) in one kidney via an inferior renal artery branch. Angiography was performed immediately before and after embolization and prior to killing at 6 months (180 ± 7 days, n = 3) and 12 months (365 ± 10 days, 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. Results: 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 6 months to 1.9{\%} ± 0.4{\%} at 12 months. 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. Conclusion: No systemic toxicity was observed in the animals 6 and 12 months after CMC/CN microspheres delivery. The local tissue response was mild.",
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N2 - Purpose: 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. Materials and Methods: Six rabbits were embolized with CMC/CN microspheres (300–500 µm) in one kidney via an inferior renal artery branch. Angiography was performed immediately before and after embolization and prior to killing at 6 months (180 ± 7 days, n = 3) and 12 months (365 ± 10 days, 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. Results: 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 6 months to 1.9% ± 0.4% at 12 months. 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. Conclusion: No systemic toxicity was observed in the animals 6 and 12 months after CMC/CN microspheres delivery. The local tissue response was mild.

AB - Purpose: 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. Materials and Methods: Six rabbits were embolized with CMC/CN microspheres (300–500 µm) in one kidney via an inferior renal artery branch. Angiography was performed immediately before and after embolization and prior to killing at 6 months (180 ± 7 days, n = 3) and 12 months (365 ± 10 days, 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. Results: 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 6 months to 1.9% ± 0.4% at 12 months. 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. Conclusion: No systemic toxicity was observed in the animals 6 and 12 months after CMC/CN microspheres delivery. The local tissue response was mild.

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KW - Local effect

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