title: Nanocoating with titanium reduces iC3b- and granulocyte-activating immune response against glutaraldehyde-fixed bovine pericardium: a new technique to improve biologic heart valve prosthesis durability?
abstract: OBJECTIVE
  An IgG and granulocyte-activating immune response with secondary dystrophic calcification might be the reason glutaraldehyde (GA)-fixed xenograft valves fail, especially in young patients, who are more immunocompetent than the elderly. Titanium nanocoating on GA-fixed bovine pericardium was tested for its ability to prevent major immunoreactions.
  
  
  METHODS
  The immune activity of platelets from GA-fixed bovine pericardium with different treatment procedures was evaluated using the blood from 5 human donors: group I (n = 5), GA fixed as the control; group 2 (n = 5), detoxified with 10% citric acid; group 3 (n = 5), 10% citric acid, aldehyde-dehydrogenase, and a physical plasma treatment; and group 4 (n = 5), treated the same as group 3, but with an additional titanium coat 30 nm in thickness. Titanium deposition was visualized using scanning electron microscopy. IgG deposits (iC3b) were shown by immunostaining and documented as colored pixels (red). The pixels were evaluated electronically. Attracted granulocytes (polymorphonuclear leukocytes) were counted in front of the titanium-coated surface.
  
  
  RESULTS
  IC3b deposits and polymorphonuclear leukocytes within control group 1 were defined as 100%; in group 2, iC3b was 149% ± 34% and polymorphonuclear leukocytes were 89%, in group 3, IC3b was 102% ± 24% and polymorphonuclear leukocytes were 47%; and in group 4, IC3b had decreased to 38.49% ± 21% (P < .05) and polymorphonuclear leukocyte activation had decreased to 6.3% (P ≤ .01).
  
  
  CONCLUSIONS
  Titanium coating significantly reduced the iC3b and granulocyte activating immune response of GA-fixed pericardium. Therefore, it might prevent relevant immunorejection and increase the durability of GA-fixed bioprosthetic heart valves.
authors.affiliation: Klinik für Herz und Thorakale Gefäßchirurgie, UK-SH Campus Lübeck, Lübeck, Germany. Norbert.Guldner@uk-sh.de
authors.forename: Norbert W
authors.initials: NW
authors.lastname: Guldner
authors.forename: Fabienne
authors.initials: F
authors.lastname: Bastian
authors.forename: Günther
authors.initials: G
authors.lastname: Weigel
authors.forename: Hanngörg
authors.initials: H
authors.lastname: Zimmermann
authors.forename: Markus
authors.initials: M
authors.lastname: Maleika
authors.forename: Michael
authors.initials: M
authors.lastname: Scharfschwerdt
authors.forename: Daniel
authors.initials: D
authors.lastname: Rohde
authors.forename: Hans-Hinrich
authors.initials: HH
authors.lastname: Sievers
mesh_terms: D000818:Animals; D001705:Bioprosthesis; D002417:Cattle; D020099:Coated Materials, Biocompatible; D003179:Complement C3b / Q000276:immunology*; D005404:Fixatives / Q000633:toxicity*; D005976:Glutaral / Q000633:toxicity*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006098:Granulocytes / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects / Q000295:instrumentation*; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D036103:Nanotechnology; D009942:Organometallic Compounds / Q000494:pharmacology*; D010496:Pericardium / Q000276:immunology / Q000637:transplantation*; D011475:Prosthesis Failure; D016707:Tissue Fixation
chemical_list: D020099:Coated Materials, Biocompatible; D005404:Fixatives; D007166:Immunosuppressive Agents; D009942:Organometallic Compounds; C507195:tetrakis(dimethylamido)titanium; D003179:Complement C3b; D005976:Glutaral