Collagen from a native tissue is fixed with a polyepoxy compound (PC) for use as a new biologic prosthetic material. Prior studies have shown that this biomaterial has comparable properties with collagen fixed with glutaraldehyde (GA), and thus has great promise for biomedical applications. A prior kinetic study indicated that the reaction between the functional groups of collagen and the multifunctional epoxy EX-313 is a 2.5th-order reaction. The purpose of this study was to understand the mechanism of the amino acid-PC reactions in a fixation process. Bovine arteries were fixed with a monofunctional PC (EX-131) and a multifunctional PC (EX-313) as a function of fixation time. A sequential fixation with a second fixative was used to identify the available remaining reactive sites from a prior fixation. The denaturation temperature (Td) was measured on each sample. Because the denaturation temperature is a direct indication of crosslinking of individual amino acids with the fixative, the increase in Td of a subsequent fixation may be indicative of the available remaining amino acids. The fixation index was measured on each sample to reflect the increase of fixation completion in a sequential fixation process. The fixation index and crosslink data also revealed that the reactive amino acids for EX-131 and EX-313 may not be exactly the same. The data in this study suggest that a monofunctional fixative can pre-react with the amino acids of collagen to effectively block further fixation of collagen with a second fixative. This amino acid masking may be associated with collagen branching. Collagen branching and its effect on denaturation temperature are described.

These in vitro studies show that a tissue aortic valve designed on the basis of the proved engineering principle that form follows function has better hemodynamics, flow dynamics, stress distribution, and durability when compared under identical in vitro conditions with an excellent commercially available tissue aortic valve.

A new biomaterial has been developed by fixing native collagen with a polyepoxy compound (PC) fixative. In this study, bovine internal thoracic arteries were fixed with PC under various conditions to help understand the kinetics of the collagen-PC reactions and optimize the fixation process. At predetermined time intervals, small samples were cut from the arteries to determine the quantities of the remaining unreacted amino acids in the collagen. Temperature, concentration, and solution pH were among the key parameters studied. The overall fixation rate was found to be reaction-rate controlled, as the rate of fixation was relatively slow compared with the rate of diffusion of PC. As might be expected, the reaction rate was favored by a higher temperature, concentration, and solution pH. A kinetic model, with a 2.5th reaction order with respect to the reactive functional groups of collagen and a first order with respect to PC, was developed that gave a good fit to the experimental data. Based on this model, the degree of fixation, X, as a function of time, t, is given by (1 - X)-1.5 = 1 + Kt, where K is a constant related to the initial concentrations and the reaction rate constant.

In vitro experiment was performed on a stented bovine jugular vein valve (VV, 14 mm I.D. x 2 cm long) and a stentless bovine jugular vein valve conduit (10 mm I.D. x 6 cm long) in a hydraulic flow loop with a downstream oscillatory pressure source to mimic respiratory changes. Simultaneous measurements were made on the valve opening area, conduit and sinus diameter changes using a specially designed laser optic system. Visualization of flow fields both proximal and distal to the venous valve, and the valve opening area were simultaneously recorded by using two video cameras. Laser Doppler anemometer surveys were made at three cross sections: the valve inlet, the valve exist, and 2 cm downstream of the venous valve to quantity flow reflux at valve closure. The experiment confirmed that the VV is a pressure-operated rather than a flow-driven device and that little or no reflux is needed to close the valve completely. The experiment further demonstrated that the VV sinus expands rapidly against back pressure, a critical character to consider in venous prosthesis design.