Detoxification and Endothelialization of Glutaraldehyde-Fixed Bovine Pericardium With Titanium Coating : A New Technology for Cardiovascular Tissue Engineering

Endothelial cell seeding of glutardialdehyde-fixed biological heart valves is hypothesized to improve biocompatibility and durability; however, the toxicity of glutardialdehyde prevents its use as a biological coating. Therefore, different detoxification strategies are applied, including surface coa...

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Published in:	Circulation (New York, N.Y.) Vol. 119; no. 12; pp. 1653 - 1660
Main Authors:	GULDNER, Norbert W, JASMUND, Inka, ZIMMERMANN, Hanngörg, HEINLEIN, Markus, GIMDT, Britta, MEIER, Veronika, FLÜSS, Florian, ROHDE, Daniel, GEBERT, Andreas, SIEVERS, Hans-Hinrich
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 31-03-2009
Subjects:	Aldehyde Dehydrogenase Animals Biological and medical sciences Bioprosthesis Blood and lymphatic vessels Cardiology. Vascular system Cattle Cell Culture Techniques Cell Survival Citric Acid Coated Materials, Biocompatible Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Endothelial Cells - cytology Fixatives Glutaral Heart Valve Prosthesis Humans Medical sciences Neuropharmacology Pericardium - cytology Pharmacology. Drug treatments Plasma Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Tissue Engineering - methods Titanium Bovine valves Glycoprotein Cardiovascular disease Endothelium Pericardium Endothelialization Vertebrata Mammalia Animal Surgery Collagen Titanium Artiodactyla Coating Ungulata vessels
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Summary:	Endothelial cell seeding of glutardialdehyde-fixed biological heart valves is hypothesized to improve biocompatibility and durability; however, the toxicity of glutardialdehyde prevents its use as a biological coating. Therefore, different detoxification strategies are applied, including surface coating with titanium, before in vitro endothelialization of glutaraldehyde-fixed bovine pericardium as the base material for prosthetic heart valves. Bovine pericardium was fixed with 0.25% glutardialdehyde. Detoxification was performed with citric acid, aldehyde dehydrogenase, and plasma deposition with titanium at low temperatures of 30 degrees C to 35 degrees C. Toxic glutaraldehyde ligands were quantified photometrically, and the vitality of seeded cells was tested to validate detoxification methods. Detoxification agents and titanium coating were applied before seeding with human endothelial cells. Endothelial cells were visualized by electron microscopic surface scanning. To evaluate cell adhesion, shear stress was applied by a flow of 5 L/min over 24 hours. Compared with untreated glutaraldehyde-fixed samples, treatment with the different agents reduced free aldehyde groups gradually (citric acid 5% < citric acid 10% < titanium < aldehyde dehydrogenase). A combination of citric acid 10%, aldehyde dehydrogenase, and titanium coating resulted in a reduction of free aldehyde ligands to 17.3+/-4.6% (P < or = 0.05) and demonstrated a vitality of seeded cells of 94+/-6.7% (P < or = 0.05). This procedure yielded a completely confluent layer of regular human endothelial cells (n=5). After application of shear stress for 24 hours on these endothelial layers, cell vitality was 81%. Titanium coating combined with chemical procedures yielded significant detoxification and complete endothelialization of conventional glutaraldehyde-fixed pericardium. This new technique might improve glutardialdehyde-fixed cardiovascular bioimplants for better biocompatibility and longer durability.
ISSN:	0009-7322 1524-4539
DOI:	10.1161/CIRCULATIONAHA.108.823948