Fixation of bioprosthetic tissues with monofunctional and multifunctional polyepoxy compounds

Abstract

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.

Characterization and biocompatibility of epoxy-crosslinked dermal sheep collagens

“…A reduction in T s was obtained, especially in N-DSC, which indicates that masking of an amine group resulted in a partial distortion of the triple-helix conformation. 20,24,25 Evaluation of the implants showed that BD45, BD90, and BD45EN were biocompatible in the sense of noncytotoxicity. BD45HAc was the exception, judging particularly from the more intense tissue reaction at day 2, although this early cytotoxic reaction had already subsided at day 5.…”

Collagen modified with epoxidized safrole for improving antibacterial activity

“…Modication of collagen with epoxidized safrole, 5-(oxiran-2-ylmethyl)-benzo[d] [1,3]dioxole (OYBD) under alkaline condition resulted in a modied collagen with increased thermal stability, enhanced mechanical properties, improved hydrophobic properties together with more density intermicro-brillar structure. Especially, the introduction of OYBD did not destroy the triple helix conformation of native collagen according to FTIR and CD analysis.…”

“…5 Additionally, cross-linking with epoxy compound showed no signs of cytotoxic degradation products. 9,10 To improve the antibacterial activity of collagen, we synthesized a new modier in this study, named 5-(oxiran-2-ylmethyl)-benzo[d] [1,3]dioxole (OYBD), derived from natural safrole (4-allyl-1,2-(methylenedioxy)benzene). This modier contained an epoxy group and a piperonyl group.…”

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An epoxidized safrole, 5-(oxiran-2-ylmethyl)-benzo [d] [1,3]dioxole (OYBD), was synthesized and employed to modify collagen for improving its antibacterial activity. The interaction between collagen and OYBD, and the structure/properties of the modified collagen were investigated in detail.

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Preparation and Properties of Gelatin Fibers Fabricated by Dry Spinning

“…This reaction is referred to as the Maillard reaction, which crosslinks between the amino groups of proteins by furfural compounds resulting from the Amadori rearrangement of reducing sugars [12] and induces physical changes in gelatin and other protein matrices [13][14][15][16]. The crosslinking of soft collagen with epoxy compounds has been reported to enhance biomechanical properties while maintaining good biocompatibility [17,18]. Epoxy compounds have also been used as crosslinkers to coat gelatin onto the inner surface of polyurethane for vascular graft applications, resulting in significantly improved cell adhesion, spreading, and proliferation [16].…”