title: In vivo biomechanical assessment of triglycidylamine crosslinked pericardium.
abstract: While glutaraldehyde crosslinking is most often used to fabricate bioprosthetic heart valves (BHV) using heterograft tissues, it predisposes BHV to calcification and dramatically stiffens the heterograft tissues. Our group previously reported the synthesis and characterization of a novel epoxy-crosslinker, triglycidylamine (TGA). TGA pretreatment of BHV tissues compared to glutaraldehyde results in both calcification resistance in subdermal implants and improved leaflet compliance. In these prior studies, optimal calcification inhibition was noted with the combined use of TGA with mercapto-aminobisphosphonate (MABP). In the present study, we investigated the hypothesis that bovine pericardium cross-linked with TGA-MABP retains these beneficial biomechanical properties in vivo using a novel mitral valve anterior leaflet (MVAL) ovine valvuloplasty model. Bovine pericardial specimens were crosslinked with either glutaraldehyde or TGA-MABP, from which 1cm2 sections were implanted in the ovine MVAL after removal of the original tissue of the same size. An array of four sonomicrometry transducers were implanted on the corners and used to compute the complete in-surface strain tensor cardiac cycle over the cardiac cycle at 0 and 4 weeks. Following explant samples were fixed in formalin for histology studies. At 4 weeks both treatment groups experienced no dimensional changes in the unloaded state, indicating no shrinkage. When fully loaded during peak systolic ejection, TGA-MABP valvuloplasty patches were significantly more compliant, which did not change at 4 weeks. In contrast, the glutaraldehyde areal strain increased significantly by 4 weeks. Estimated implant stresses for both treatment groups, based on previously measured biomechanical properties [Connolly JM, Alferiev I, Clark-Gruel JN, Eidelman N, Sacks M, Palmatory E, et al. Triglycidylamine crosslinking of porcine aortic valve cusps or bovine pericardium results in improved biocompatibility, biomechanics, and calcification resistance: chemical and biological mechanisms. Am J Pathol 2005;166(1):1-13], were 40 and 250 kPa in the circumferential and radial directions, respectively, which are comparable to predicted BHV peak stress levels. We conclude that TGA-MABP crosslinked bovine pericardium, when subjected to in vivo BHV stress levels in a blood-contacting environment, maintains stable functionality.
authors.affiliation: Department of Bioengineering, Engineered Tissue Mechanics Laboratory, McGowan Institute for Regenerative Medicine, 100 Technology Drive, Room 234, University of Pittsburgh, Pittsburgh, PA 15219, USA. msacks@pitt.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sacks
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Hamamoto
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Connolly
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Gorman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Levy
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001696:Biomechanical Phenomena; D002417:Cattle; D003432:Cross-Linking Reagents; D004164:Diphosphonates; D004852:Epoxy Compounds; D005976:Glutaral; D006350:Heart Valve Prosthesis; D008297:Male; D008943:Mitral Valve; D010496:Pericardium; D012756:Sheep; D013438:Sulfhydryl Compounds