Skip to main content
Log in

Experimental Liver Embolization with Four Different Spherical Embolic Materials: Impact on Inflammatory Tissue and Foreign Body Reaction

  • Laboratory Investigation
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

We sought to describe and compare material specific inflammatory and foreign body reactions after porcine liver embolization with spherical embolic agents. In 40 animals, superselective liver embolization was performed with four different spherical embolic agents of various sizes: 40–120 μm (Embozene, Embosphere), and 100–300 μm, 500–700 μm, and 700–900 μm (Embozene, Embosphere, Bead Block, and Contour SE, respectively). After 4 or 12 weeks, inflammatory reactions were evaluated microscopically according to the Banff 97 classification. For investigation of foreign body reactions, a newly designed giant cell score was applied. Banff 97 and giant cell scores closely correlated. At 4 weeks, small Embosphere particles (100–300 μm) had a significantly higher Banff 97 score than Embozene, Bead Block, and Contour SE of the corresponding size. After 12 weeks, the calculated differences were not statistically significant. Comparison between the 4-week results and the 12-week results revealed a statistically higher Banff 97 score for Embosphere 100–300 μm after 4 weeks than after 12 weeks (P = 0.02). The overall foreign body reaction was pronounced after embolization with smaller particles, especially in small Embosphere particles. Giant cell numbers with Embosphere 100–300 μm were statistically higher compared with the other materials of corresponding size (P < 0.0001). Inflammatory and giant cell reactions after embolization procedures depend on the embolic material. The overall inflammatory reaction was low. However, marked inflammation was associated with small Embosphere particles at 4 weeks, a finding that might be caused by the allogeneic overcoat. Correspondingly, giant cells indicating a foreign body reaction were more frequently associated with small particle sizes, especially after embolization with small Embosphere particles.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37:429–442

    Article  PubMed  CAS  Google Scholar 

  2. Beaujeux R, Laurent A, Wassef M et al (1996) Trisacryl gelatin microspheres for therapeutic embolization, II: preliminary clinical evaluation in tumors and arteriovenous malformations. AJNR Am J Neuroradiol 17:541–548

    PubMed  CAS  Google Scholar 

  3. Pelage JP, Le Dref O, Soyer P et al (2000) Fibroid-related menorrhagia: treatment with superselective embolization of the uterine arteries and midterm follow-up. Radiology 215:428–431

    PubMed  CAS  Google Scholar 

  4. Richter GM, Radeleff B, Rimbach S et al (2004) Uterine fibroid embolization with spheric micro-particles using flow guiding: safety, technical success and clinical results. Rofo 176:1648–1657

    PubMed  CAS  Google Scholar 

  5. Sun S, Lang EV (1998) Bone metastases from renal cell carcinoma: preoperative embolization. J Vasc Interv Radiol 9:263–269

    Article  PubMed  CAS  Google Scholar 

  6. Siskin GP, Dowling K, Virmani R et al (2003) Pathologic evaluation of a spherical polyvinyl alcohol embolic agent in a porcine renal model. J Vasc Interv Radiol 14:89–98

    PubMed  Google Scholar 

  7. Borovac T, Pelage JP, Kasselouri A et al (2006) Release of ibuprofen from beads for embolization: in vitro and in vivo studies. J Control Release 115:266–274

    Article  PubMed  CAS  Google Scholar 

  8. Colgan TJ, Pron G, Mocarski EJ et al (2003) Pathologic features of uteri and leiomyomas following uterine artery embolization for leiomyomas. Am J Surg Pathol 27:167–177

    Article  PubMed  Google Scholar 

  9. Stampfl S, Stampfl U, Rehnitz C et al (2007) Experimental evaluation of early and long-term effects of microparticle embolization in two different mini-pig models. Part II: liver. Cardiovasc Intervent Radiol 30:462–468

    Article  PubMed  CAS  Google Scholar 

  10. Bayne K (1996) Revised Guide for the Care and Use of Laboratory Animals available. American Physiological Society. Physiologist 39:199, 208–111

  11. Racusen LC, Solez K, Colvin RB et al (1999) The Banff 97 working classification of renal allograft pathology. Kidney Int 55:713–723

    Article  PubMed  CAS  Google Scholar 

  12. Khankan AA, Osuga K, Hori S et al (2004) Embolic effects of superabsorbent polymer microspheres in rabbit renal model: comparison with tris-acryl gelatin microspheres and polyvinyl alcohol. Radiat Med 22:384–390

    PubMed  Google Scholar 

  13. Jones JA, Chang DT, Meyerson H et al (2007) Proteomic analysis and quantification of cytokines and chemokines from biomaterial surface-adherent macrophages and foreign body giant cells. J Biomed Mater Res A 83:585–596

    PubMed  Google Scholar 

  14. Luttikhuizen DT, Harmsen MC, Van Luyn MJ (2006) Cellular and molecular dynamics in the foreign body reaction. Tissue Eng 12:1955–1970

    Article  PubMed  CAS  Google Scholar 

  15. Ratner BD, Bryant SJ (2004) Biomaterials: where we have been and where we are going. Annu Rev Biomed Eng 6:41–75

    Article  PubMed  CAS  Google Scholar 

  16. Anderson JM (2001) Biological responses to materials. Annu Rev Mater Res 31:81–110

    Article  CAS  Google Scholar 

  17. Miller KM, Anderson JM (1989) In vitro stimulation of fibroblast activity by factors generated from human monocytes activated by biomedical polymers. J Biomed Mater Res 23:911–930

    Article  PubMed  CAS  Google Scholar 

  18. Miller KM, Rose-Caprara V, Anderson JM (1989) Generation of IL-1-like activity in response to biomedical polymer implants: a comparison of in vitro and in vivo models. J Biomed Mater Res 23:1007–1026

    Article  PubMed  CAS  Google Scholar 

  19. Bonfield TL, Colton E, Anderson JM (1991) Fibroblast stimulation by monocytes cultured on protein adsorbed biomedical polymers. I. Biomer and polydimethylsiloxane. J Biomed Mater Res 25:165–175

    Article  PubMed  CAS  Google Scholar 

  20. Gretzer C, Emanuelsson L, Liljensten E et al (2006) The inflammatory cell influx and cytokines changes during transition from acute inflammation to fibrous repair around implanted materials. J Biomater Sci Polym Ed 17:669–687

    Article  PubMed  CAS  Google Scholar 

  21. Bonfield TL, Colton E, Marchant RE et al (1992) Cytokine and growth factor production by monocytes/macrophages on protein preadsorbed polymers. J Biomed Mater Res 26:837–850

    Article  PubMed  CAS  Google Scholar 

  22. Bonfield TL, Anderson JM (1993) Functional versus quantitative comparison of IL-1 beta from monocytes/macrophages on biomedical polymers. J Biomed Mater Res 27:1195–1199

    Article  PubMed  CAS  Google Scholar 

  23. Luttikhuizen DT, Dankers PY, Harmsen MC et al (2007) Material dependent differences in inflammatory gene expression by giant cells during the foreign body reaction. J Biomed Mater Res A 83:879–886

    PubMed  CAS  Google Scholar 

  24. Huang Y, Liu X, Wang L et al (2003) Long-term biocompatibility evaluation of a novel polymer-coated stent in a porcine coronary stent model. Coron Artery Dis 14:401–408

    Article  PubMed  Google Scholar 

  25. Richter GM, Stampfl U, Stampfl S et al (2005) A new polymer concept for coating of vascular stents using PTFEP (poly(bis(trifluoroethoxy)phosphazene) to reduce thrombogenicity and late in-stent stenosis. Invest Radiol 40:210–218

    Article  PubMed  CAS  Google Scholar 

  26. Stampfl S, Stampfl U, Bellemann N et al (2008) Biocompatibility and recanalization characteristics of hydrogel microspheres with polyzene-F as polymer coating. Cardiovasc Intervent Radiol 31:799–806

    Article  PubMed  Google Scholar 

  27. Stampfl S, Bellemann N, Stampfl U et al (2008) Inflammation and recanalization of four different spherical embolization agents in the porcine kidney model. J Vasc Interv Radiol 19:577–586

    Article  PubMed  Google Scholar 

  28. Laurent A, Beaujeux R, Wassef M et al (1996) Trisacryl gelatin microspheres for therapeutic embolization, I: development and in vitro evaluation. Am J Neuroradiol 17:533–540

    PubMed  CAS  Google Scholar 

  29. Anderson JM, Rodriguez A, Chang DT (2008) Foreign body reaction to biomaterials. Semin Immunol 20:86–100

    Article  PubMed  CAS  Google Scholar 

  30. Anderson JM, Defife K, McNally A et al (1999) Monocyte, macrophage and foreign body giant cell interactions with molecularly engineered surfaces. J Mater Sci Mater Med 10:579–588

    Article  PubMed  CAS  Google Scholar 

  31. Moreira PL, An YH (2003) Animal models for therapeutic embolization. Cardiovasc Intervent Radiol 26:100–110

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was sponsored in part by CeloNova BioSciences Inc., Newnan, GA. Drs. Stampfl, Lopez, and Richter have had sponsored research agreements with CeloNova. Dr. Richter has a consultant agreement with CeloNova.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Goetz M. Richter.

Additional information

Ulrike Stampfl and Sibylle Stampfl contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stampfl, U., Stampfl, S., Bellemann, N. et al. Experimental Liver Embolization with Four Different Spherical Embolic Materials: Impact on Inflammatory Tissue and Foreign Body Reaction. Cardiovasc Intervent Radiol 32, 303–312 (2009). https://doi.org/10.1007/s00270-008-9495-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-008-9495-1

Keywords

Navigation