title: Structural requirements for stabilization of vascular elastin by polyphenolic tannins.
abstract: Elastin-associated degeneration and calcification are potential causes of long-term failure of glutaraldehyde (Glut) fixed tissue bioprostheses used in cardiovascular surgery. This vulnerability may be attributed to the inability of Glut to cross-link and adequately protect vascular elastin from enzymatic attack. Tannic acid (TA), a poly galloyl glucose (Glc), is compatible with Glut fixation, binds to vascular elastin, improves resistance to degradation and reduces in vivo calcification. While these results provided evidence of a beneficial interaction between elastin and TA, the nature and mechanisms of these interactions are unclear; moreover, TA-elastin binding exhibits a partial instability after long-term interaction with vascular elastin which could contribute to issues of implant toxicity. In present studies, we used resistance to elastase, mechanical properties, and cell viability assays to evaluate the elastin-stabilizing potential and cytotoxicity of TA derivatives and individual TA components such as acetylated TA (AcTA), pentagalloylglucose (PGG), free gallic acid (Gall) and Glc. Our comparative study demonstrates that polyphenolic hydroxyl groups are the main structural groups essential to the interaction between TA and elastin. Furthermore, we show that PGG, the core structure of TA, possesses the same unique elastin-stabilizing qualities of TA, yet it is much less cytotoxic than TA and thus could be potentially useful as an elastin-stabilizing agent for cardiovascular bioprostheses.
authors.affiliation: Cardiovascular Implant Research Laboratory, Department of Bioengineering, Clemson University, 501 Rhodes Engineering Research Center, Clemson, SC 29634, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Isenburg
authors.forename: Nishant V
authors.initials: NV
authors.lastname: Karamchandani
authors.forename: Dan T
authors.initials: DT
authors.lastname: Simionescu
authors.forename: Narendra R
authors.initials: NR
authors.lastname: Vyavahare
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001696:Biomechanical Phenomena; D001705:Bioprosthesis; D001808:Blood Vessels / Q000033:anatomy & histology / Q000737:chemistry* / Q000187:drug effects* / Q000502:physiology; D003432:Cross-Linking Reagents; D004355:Drug Stability; D004549:Elastin / Q000737:chemistry* / Q000187:drug effects*; D005404:Fixatives; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005976:Glutaral; D008422:Materials Testing; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D013552:Swine; D013634:Tannins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D005404:Fixatives; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013634:Tannins; D004549:Elastin; D005976:Glutaral