Biomaterials 26 (2005) 795–804 The effects of collagen fiber orientation on the flexural properties of pericardial heterograft biomaterials Ali Mirnajafi a , Jeremy Raymer a , Michael J. Scott b , Michael S. Sacks a, * a Engineered Tissue Mechanics Laboratory, Department of Bioengineering, McGowan Institute for Regenerative Medicine, Room 234, 100 Technology Drive, University of Pittsburgh, Pittsburgh, PA 15219, USA b Edwards Lifesciences, Irvine, CA, USA Received 7 December 2003; accepted 13 March 2004 Abstract Improving cardiac valve bioprostheses (BHV) utilizing heterograft biomaterials requires a better understanding of their mechanical behavior. Flexure is a major mode of deformation for BHV leaflets during valve operation, inducing more complex deformation patterns within the tissue compared to tensile loads. In this study, we investigated the relation between collagen fiber preferred direction and the resulting flexural properties of native and glutaraldehyde-treated bovine pericardium. 20mm  4mm strips were cut from the presorted sheets of bovine pericardium and divided into four groups: two directions of collagen fiber orientation in two groups of native and chemically treated specimens. Specimens were flexed in two different directions using a three-point bending technique (ASAIO J. 45(1999)59) and their flexural mechanical response compared. Results indicated that: (1) the relationship between the applied flexing moment and change of curvature of specimens was non-linear in both native and chemically fixed groups, (2) there were no directional differences in flexural properties when the bovine pericardium is flexed towards either the epi-pericardial or visceral surfaces in both native and chemically fixed specimens, (3) native and chemically fixed bovine pericardium were stiffer when flexed perpendicular to local preferred collagen fiber direction, and (4) chemical fixation increased the flexural rigidity of bovine pericardium. Results of this study indicate that the flexural properties of bovine pericardium are dominated by inter-fiber cross-links as opposed to the stiffness of the collagen fibers themselves. These findings can be used to guide the development of novel chemical treatment methods that seek to optimize biomechanical properties of heterograft biomaterials. r 2004 Elsevier Ltd. All rights reserved. Keywords: Pericardium; Bioprosthetic heart valves; Collagen orientation; Flexural properties; Heterograft biomaterials 1. Introduction The main advantages of bioprosthetic heart valves (BHV) continue to be their excellent hemodynamic performance and low thrombogenicity [1,2]. Currently, porcine aortic valve and bovine pericardium are the two preferred soft tissue sources for heterograft biomaterials used in commercially available BHV. Of these two types, second generation pericardial BHV generally display better durability than their discontinued predecessors, and appear to be as durable as the best porcine BHV [3]. An advantage of pericardial heterograft biomaterials is their amenability to design, as there are no anatomic restrictions associated with the native porcine aortic valve geometry. Irrespective of the specific heterograft bioma- terials used, BHV continue to suffer from limited long- term durability, with an average lifespan of 10–15 years [3]. Calcification [4] and mechanically induced fatigue damage [5–7] are known to be the major causes of failure. Heterograft biomaterials will continue to be utilized in fabricating replacement prosthetic valves for the foreseeable future. There have been many attempts to improve heterograft biomaterial durability through novel chemical treatments. For example, dye-mediated photo-oxidation has been shown to be resistant to mineralization and in vitro chemical and enzymatic degradation, supportive to endothelial cell growth, and to be stable in vivo [8–11]. However, pericardial BHV made utilizing this chemical treatment have met with poor clinical outcomes exclusively due to structural failures, a result of both faulty valve design and poor tissue durability [12]. ARTICLE IN PRESS *Corresponding author. Tel.: +1-412-235-5146; fax: +1-412-235- 5160. E-mail address: msacks@pitt.edu (M.S. Sacks). 0142-9612/$-see front matter r 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2004.03.004