Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                
Skip to main content
Springer Nature Link
Log in

Biocompatibility screening in cardiovascular implants

Biokompatibilitätsuntersuchungen an kardiovaskulären Implantaten

  • ORIGINAL PAPER
  • Published:
Zeitschrift für Kardiologie Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Zunehmendes Interesse gilt der Biokompatibilität kardiovaskulärer Implantate. Ziel dieser Arbeit ist die Vorstellung von Methoden und Ergebnissen der pathologischen Aufarbeitung von explantierten Implantaten.

Methoden

Die Standardeinbettung von Implantaten zur histologischen Beurteilung in Paraffin ist nur eingeschränkt geeignet, da metallische Anteile vor der Einbettung unter Beschädigung der Grenzfläche Gewebe/Implantat entfernt werden müssen. Alternativ kommt eine Einbettung in Kunstharze in Frage, wobei histologische Schnitte mittels Schneiden und Schleifen angefertigt werden. Dies ermöglicht die Untersuchung lokaler entzündlicher Vorgänge an der Oberfläche des Implantates. Zusätzlich interessieren bei der Aufarbeitung der Implantate die Reaktion und Struktur des umgebenden Gewebes sowie der benachbarten Grenzfläche zum Blutstrom. Neben der Histologie kommen immunhistochemische Verfahren sowie die Elektronenmikroskopie zum Einsatz. Unter Verwendung der genannten Methoden demonstrieren wir Befunde von Implantatpräparaten aus Tierversuchen und entsprechende Ergebnisse von Implantaten, die bei Patienten im Rahmen von Korrekturoperationen bei angeborenen Herzfehlern entfernt wurden.

Ergebnisse

Nach der Implantation kommt es unabhängig vom Implantattyp zu einer raschen Re-Endothelialisierung der Gefäßoberfläche. In das nach Okkluder-Implantation initial gebildete Thrombusgewebe sprossen fibromuskuläre Zellen ein, wie sie auch nach Stentimplantation in der Intimahyperplasie gesehen werden. Entzündliche Reaktionen sind in Qualität und zeitlichem Verlauf materialabhängig.

Zusammenfassung

Mit einer vollständigen pathologischen Aufarbeitung kardiovaskulärer Implantate nach Explantation können Informationen über Einwachsen, Endothelialisierung und Entzündungsreaktionen gewonnen werden.

Summary

Background

Interest in information on biocompatibility of implants is increasing. The purpose of this paper is to discuss methods and results of pathological biocompatibility screening of explanted cardiovascular implants.

Methods

Use of standard histology after embedding in paraffin is limited since metallic implants have to be removed during workup with disruption of the specimen. Alternatively, tissue blocks containing an implant can be embedded in methylmethacrylate or hydroxyethylmethacrylate and processed by sectioning with a diamond cutter and grinding, thus leaving the implant in situ and saving the tissue/implant interface for detection of local inflammatory reactions. Another important aspect of evaluation is the progress of thrombus organisation after initial fibrin clotting on the metal surface or in the inner part of occlusion devices. New methacrylate resins and embedding techniques allow for specific immunohisto-chemical staining of the specimen thus enabling characterisation of tissues surrounding the implant. Information on endothelialisation of the vascular surface of the implant can be obtained by means of immunohistochemistry or by scanning electron microscopy.

Results

Illustrating the use of these technologies, we demonstrate findings in tissue specimens from animal studies with different types of devices (i.e. stents, occlusion devices). We present corresponding findings in human specimens with implants that were removed during corrective surgery for congenital heart defects. Early endothelialisation of the vascular surface was seen after implantation in all types of devices. Cells within occlusion devices could be characterised histologically and immunohistochemically as fibromuscular cells as seen in intimal hyperplasia after stent implantation. Inflammatory implant-host reactions ranged from mild to moderate (medical grade stainless steel, nitinol) to severe (polytetrafluoroethylene [PTFE]).

Conclusions

With an optimal work-up of cardiovascular implants, ingrowth and endothelialisation as well as inflammatory reactions in the surrounding tissue can be assessed. This information allows evaluation of individual tissue reactions to the implant and may serve as valuable basis for optimisation of biocompatibility by implant modification.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Anderson JM (1988) Inflammatory response to implants. ASAIO Trans 34:101–107

    CAS  PubMed  Google Scholar 

  2. Asahara T, Bauters C, Pastore C, Kearney M, Rossow S, Bunting S, Ferrara N, Symes JF, Isner JM (1995) Local delivery of vascular endothelial growth factor accelerates reendothelialization and attenuates intimal hyperplasia in balloon-injured rat carotid artery. Circulation 91:2793–2801

    CAS  PubMed  Google Scholar 

  3. Barth KH, Strandberg JD, Kaufman SL, White RI Jr (1978) Chronic vascular reactions to steel coil occlusion devices. AJR Am J Roentgenol 131:455–458

    CAS  PubMed  Google Scholar 

  4. Bellon JM, Bujan J, Contreras LA, Hernando A, Jurado F (1996) Similarity in behavior of polytetrafluoroethylene (ePTFE) prostheses implanted into different interfaces. J Biomed Mater Res 31:1–9

    Article  CAS  PubMed  Google Scholar 

  5. Crook MF, Akyurek LM (2003) Gene transfer strategies to inhibit neointima formation. Trends Cardiovasc Med 13:102–106

    Article  CAS  PubMed  Google Scholar 

  6. Farb A, Sangiorgi G, Carter AJ, Walley VM, Edwards WD, Schwartz RS, Virmani R (1999) Pathology of acute and chronic coronary stenting in humans. Circulation 99:44–52

    CAS  PubMed  Google Scholar 

  7. Fingerle J, Au YP, Clowes AW, Reidy MA (1990) Intimal lesion formation in rat carotid arteries after endothelial denudation in absence of medial injury. Arteriosclerosis 10:1082–1087

    CAS  PubMed  Google Scholar 

  8. French MH, Faxon DP (2002) Current anticoagulation options in percutaneous intervention: designing patient-specific strategies. Rev Cardiovasc Med 3:176–182

    Article  PubMed  Google Scholar 

  9. Harnek J, Zoucas E, Carlemalm E, Cwikiel W (1999) Differences in endothelial injury after balloon angioplasty, insertion of balloon-expanded stents or release of self-expanding stents: An electron microscopic experimental study. Cardiovasc Intervent Radiol 22:56–61

    Article  CAS  PubMed  Google Scholar 

  10. Hart CE, Kraiss LW, Vergel S, Gilbertson D, Kenagy R, Kirkman T, Crandall DL, Tickle S, Finney H, Yarranton G, Clowes AW (1999) PDGFbeta receptor blockade inhibits intimal hyperplasia in the baboon. Circulation 99:564–569

    CAS  PubMed  Google Scholar 

  11. Haynes DR, Crotti TN, Haywood MR (2000) Corrosion of and changes in biological effects of cobalt chrome alloy and 316L stainless steel prosthetic particles with age. J Biomed Mater Res 49:167–175

    Article  CAS  PubMed  Google Scholar 

  12. Hoffmann R, Mintz GS (2000) Coronary in-stent restenosis—predictors, treatment and prevention. Eur Heart J 21:1739–1749

    Google Scholar 

  13. Jux C, Bertram H, Wohlsein P, Bruegmann M, Fink C, Wueboldt P, Paul T, Hausdorf G (2001) Experimental preseeding of the STARFlex atrial septal occluder device with autologous cells. J Interv Cardiol 14:309–312

    CAS  PubMed  Google Scholar 

  14. Jux C, Bertram H, Wohlsein P, Brugmann M, Wuboldt P, Fink C, Paul T, Hausdorf G (2002) Experimental ASD closure using autologous cell-seeded interventional closure devices. Cardiovasc Res 53:181–191

    Article  CAS  PubMed  Google Scholar 

  15. Kong X, Grabitz RG, van Oeveren W, Klee D, van Kooten TG, Freudenthal F, Qing M, von Bernuth G, Seghaye MC (2002) Effect of biologically active coating on biocompatibility of Nitinol devices designed for the closure of intra-atrial communications. Biomaterials 23:1775–1783

    Article  CAS  PubMed  Google Scholar 

  16. Kretschmar O, Dahnert I, Berger F, Ewert P, Lange PE (2000) [Interventional treatment of congenital heart defects in infants with a body weight up to 2500 grams]. Z Kardiol 89:1126–1132

    Article  CAS  PubMed  Google Scholar 

  17. Krumsdorf U, Ostermayer S, Billinger K, Trepels T, Zadan E, Horvath K, Sievert H (2004) Incidence and clinical course of thrombus formation on atrial septal defect and patient foramen ovale closure devices in 1000 consecutive patients. J Am Coll Cardiol 43:302–309

    PubMed  Google Scholar 

  18. Kumar V (1999) Thrombosis. 6th ed. Saunders Company, Philadelphia, pp 124–138

  19. Kumazawa R, Watari F, Takashi N, Tanimura Y, Uo M, Totsuka Y (2002) Effects of Ti ions and particles on neutrophil function and morphology. Biomaterials 23:3757–3764

    Article  CAS  PubMed  Google Scholar 

  20. Laube HR, Duwe J, Rutsch W, Konertz W (2000) Clinical experience with autologous endothelial cellseeded polytetrafluoroethylene coronary artery bypass grafts. J Thorac Cardiovasc Surg 120:134–141

    Article  CAS  PubMed  Google Scholar 

  21. Lee JS, Adrie C, Jacob HJ, Roberts JD, Jr., Zapol WM, Bloch KD (1996) Chronic inhalation of nitric oxide inhibits neointimal formation after balloon-induced arterial injury. Circ Res 78:337–342

    CAS  PubMed  Google Scholar 

  22. Michel-Behnke I, Akinturk H, Schranz D (1999) [Reopening of a persistent left superior vena cava in the early postoperative period following bidirectional cavopulmonary anastomosis–treatment by coil embolization]. Z Kardiol 88:555–558

    Article  CAS  PubMed  Google Scholar 

  23. Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban HE, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, Molnar F, Falotico R (2002) A randomized comparison of a sirolimuseluting stent with a standard stent for coronary revascularization. N Engl J Med 346:1773–1780

    Google Scholar 

  24. Newby AC, Zaltsman AB (2000) Molecular mechanisms in intimal hyperplasia. J Pathol 190:300–309

    Article  CAS  PubMed  Google Scholar 

  25. Pauperio HM, Redington AN, Rigby ML (1996) Closing the patent ductus arterial duct-plugs, umbrellas and coils. Cardiol Young 6:252–254

    Google Scholar 

  26. Pearson JD (1999) Endothelial cell function and thrombosis. Baillieres Best Pract Res Clin Haematol 12:329–341

    Article  CAS  PubMed  Google Scholar 

  27. Peuster M, Reckers J, Fink C (2002) [Interventional therapy of large venovenous collaterals after univentricular palliation for congenital heart disease using the Starflex- and Amplatzer-PDA occluder]. Z Kardiol 91:853–857

    Article  PubMed  Google Scholar 

  28. Radomski MW, Palmer RM, Moncada S (1987) The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol 92:639–646

    CAS  PubMed  Google Scholar 

  29. Rafii S, Meeus S, Dias S, Hattori K, Heissig B, Shmelkov S, Rafii D, Lyden D (2002) Contribution of marrow-derived progenitors to vascular and cardiac regeneration. Semin Cell Dev Biol 13:61–67

    Article  CAS  PubMed  Google Scholar 

  30. Rajagopal V, Rockson SG (2003) Coronary restenosis: a review of mechanisms and management. Am J Med 115:547–553

    Article  PubMed  Google Scholar 

  31. Reul J, Weis J, Spetzger U, Konert T, Fricke C, Thron A (1997) Long-term angiographic and histopathologic findings in experimental aneurysms of the carotid bifurcation embolized with platinum and tungsten coils. Am J Neuroradiol 18:35–42

    CAS  PubMed  Google Scholar 

  32. Ries MW, Kampmann C, Rupprecht HJ, Hintereder G, Hafner G, Meyer J (2003) Nickel release after implantation of the Amplatzer occluder. Am Heart J 145:737–741

    Article  CAS  PubMed  Google Scholar 

  33. Schwartz RS, Henry TD (2002) Pathophysiology of coronary artery restenosis. Rev Cardiovasc Med 3 (Suppl 5):S4–S9

    PubMed  Google Scholar 

  34. Shi Q, Rafii S, Wu MH, Wijelath ES, Yu C, Ishida A, Fujita Y, Kothari S, Mohle R, Sauvage LR, Moore MA, Storb RF, Hammond WP (1998) Evidence for circulating bone marrow-derived endothelial cells. Blood 92:362–367

    CAS  PubMed  Google Scholar 

  35. Sigler M, Handt S, Seghaye MC, von Bernuth G, Grabitz, RG (2000) Evaluation of in vivo biocompatibility of different devices for interventional closure of the patent ductus arteriosus in an animal model. Heart 83:570–573

    Article  CAS  PubMed  Google Scholar 

  36. van der Giessen WJ, van Beusekom HM, Eijgelshoven MH, Morel MA, Serruys PW (1998) Heparin-coating of coronary stents. Semin Interv Cardiol 3:173–176

    CAS  PubMed  Google Scholar 

  37. van Kampen CL, Gibbons DF (1979) Effect of implant surface chemistry upon arterial thrombosis. J Biomed Mater Res 13:517–541

    Article  CAS  PubMed  Google Scholar 

  38. VanBelle E, Chen DH, Tio FO, Maillard L, Passeri J, Isner JM (1996) Accelerated endothelialization improves stent biocompatibility: Feasibility and effects of VEGF-gene transfer. Circulation 94:1517

    Google Scholar 

  39. Wataha JC, O’Dell NL, Singh BB, Ghazi M, Whitford GM, Lockwood PE (2001) Relating nickel-induced tissue inflammation to nickel release in vivo. J Biomed Mater Res 58:537–544

    Article  CAS  PubMed  Google Scholar 

  40. Wilcox JN, Waksman R, King SB, Scott NA (1996) The role of the adventitia in the arterial response to angioplasty: the effect of intravascular radiation. Int J Radiat Oncol Biol Phys 36:789–796

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Herzzentrum Göttingen, Pädiatrische Kardiologie und Intensivmedizin, Georg-August-Universität Göttingen, 37099, Göttingen, Germany

    M. Sigler &  T. Paul

  2. Universitätsklinik und Poliklinik für Kinderkardiologie, Martin-Luther-Universität Halle-Wittenberg, 06097, Halle, Germany

    R. G. Grabitz

Authors
  1. M. Sigler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. G. Grabitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Sigler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sigler, M., Paul, T. & Grabitz, R.G. Biocompatibility screening in cardiovascular implants. ZS Kardiologie 94, 383–391 (2005). https://doi.org/10.1007/s00392-005-0231-4

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-005-0231-4

Schlüsselwörter

Key words

Search

Navigation