The Effect of Space Fillers in the Cross-Linking Processes of Bioprosthesis

Abstract

Glutaraldehyde (GA) is largely used in the cross-linking of collagen matrices to improve their mechanical and biological properties for applications in cardiovascular surgery. However, GA has major drawbacks, including graft degeneration, calcification, and durability. The aim of this study was to test the hypothesis that filling the interstitial space in the bovine pericardium with various space fillers could prevent tissue calcification. GA, genipin, and 1-ethyl-3(-3 dimethyl aminopropyl) carbodiimide hydrochloride fixation with spacefiller treatment have been studied in order to improve the properties of heart valve xenografts. Crosslinking efficiency of GA treated group was better than genipin or 1-(3-dimethyl aminopropyl)-3-ethyl carbodiimide/N-hydroxysuccinimide treated group in vitro mechanical, enzymatic degradation resistance tests. Space-filling samples have shown significantly reduced calcification in the rabbit intramuscular implantation model. Regardless of the filling effect, the level of calcification and the cytotoxicity was low in a genipin-treated group compared to levels in the GA-treated group. The results indicated that GA and genipin fixation with space-filler treatment were effective in anticalcification for biological tissue preservation.

Chemical cross‐linking of xenopericardial biomeshes: A bottom‐up study of structural and functional correlations

“…For example, the EDC cross‐linking only slightly increased the thickness, while the HMDC and genipin samples were 1.5‐fold thicker and the EGDE group was the thickest. Similar results for UTS have been reported earlier, particularly, for genipin, EGDE, EDC and macrodiisocyanates . The reduced post‐cross‐linking Young’s Modulus anisotropy may be attributed to the preferable interfibrillar bond formation.…”

Early Results of Novel Bovine Pericardial Patch Using Comprehensive Anticalcification Procedure in a Swine Model

“…22 Although the mechanisms of space filler treatment are not fully understood, it is believed that reaction of macromolecules with free aldehyde groups of GA causes their inactivation and forms a barrier that prevents the release of residual GA. 23,24 We previously demonstrated that GA cross-linking with PEG as space filler was an effective anticalcification method in the rabbit intramuscular implantation model. 7 Vasudev et al 25 reported that PEG substantially inhibited deposits of calcium and platelet-tissue attachment. They hypothesized that PEG treatment modifies or masks the platelet receptor sites on collagen and reduces platelet density on the surface.…”

“…Therefore, there have been many studies to decrease calcification and improve the durability of xenograft. [2][3][4][5] We have been involved in the study of various issues of xenograft tissue engineering, [6][7][8][9] such as decellularization, space filler treatment, cross-linking, and detoxification. On the basis of these studies, we developed a comprehensive anticalcification procedure and produced novel bovine pericardial patch using this technique.…”

Tissue Engineering of Ureteral Grafts: Preparation of Biocompatible Crosslinked Ureteral Scaffolds of Porcine Origin

“…However, some crosslinking agents (e.g., GA) are toxic or promote the calcification of scaffolds in vivo (Khor, 1997 ; Sung et al, 1999a ; Chang et al, 2002 ; Everaerts et al, 2008 ; Koch et al, 2012 ). In the present study, the crosslinkers GA, GP, and CDI were selected in accordance with descriptions of the biocompatibility in the recent literature (Khor, 1997 ; Sung et al, 1999b ; Liang et al, 2004 ; Chang et al, 2005 ; Cao and Xu, 2008 ; Koch et al, 2012 ; Jeong et al, 2013 ).…”

“…Glutaraldehyde is an aggressive, indiscriminant crosslinking reagent that is commonly used in commercially available tissues (Badylak and Gilbert, 2008 ). GA crosslinked tissue exhibits a stabilized collagen matrix and decreased immunological reaction (Jeong et al, 2013 ; Awang et al, 2014 ). However, we observed that the immunological response (giant cells, CD68+ macrophages) in GA crosslinked ureteral scaffolds was higher compared to that in chemically untreated scaffolds.…”