The hybrid crosslinking method improved the stability and anti-calcification properties of the bioprosthetic heart valves

Abstract

The bioprosthetic heart valves (BHVs) are the best option for the treatment of valvular heart disease. Glutaraldehyde (Glut) is commonly used as the golden standard reagent for the crosslinking of BHVs. However, the obvious defects of Glut, including residual aldehyde toxicity, degradation and calcification, increase the probability of valve failure in vivo and motivated the exploration of alternatives. Thus, the aim of this study is to develop a non-glutaraldehyde hybrid cross-linking method composed of Neomycin Trisulfate, Polyethylene glycol diglycidyl ether and Tannic acid as a substitute for Glut, which was proven to reduce calcification, degradation, inflammation of the biomaterial. Evaluations of the crosslinked bovine pericardial included histological and ultrastructural characterization, biomechanical performance, biocompatibility and structural stability test, and in vivo anti-inflammation and anti-calcification assay by subcutaneous implantation in juvenile Sprague Dawley rats. The results revealed that the hybrid crosslinked bovine pericardial were superior to Glut crosslinked biomaterial in terms of better hydrophilicity, thermodynamics stability, hemocompatibility and cytocompatibility, higher Young’s Modulus, better stability and resistance to enzymatic hydrolysis, and lower inflammation, degradation and calcification levels in subcutaneous implants. Considering all above performances, it indicates that the hybrid cross-linking method is appropriate to replace Glut as the method for BHV preparation, and particularly this hybrid crosslinked biomaterials may be a promising candidate for next-generation BHVs.

Free-aldehyde neutralized and oligohyaluronan loaded bovine pericardium with improved anti-calcification and endothelialization for bioprosthetic heart valves

“…Previous studies have also demonstrated that the loss of HA in tissues is linearly correlated with calcification ( Johansson et al, 2011 ). Our previous study showed that the GAG content in pericardial tissue was only 2%–4% in pericardial tissue, which is far lower than that in valve tissue ( Song et al, 2021 ; Liu et al, 2022 ). Therefore, increasing the HA content in pericardial tissues might enhance the anticalcification properties of BHVs.…”

“…However, several drawbacks, such as residual free aldehydes, cytotoxicity, poor biocompatibility, and calcification, are frequently encountered with Glut-crosslinked BHVs ( Liu et al, 2019 ). Although many studies are exploring new crosslinking reagents or methods to replace Glut, none of them have been applied in the clinic ( Tam et al, 2015 ; Hu et al, 2021 ; Liu et al, 2022 ). Neutralizing the free aldehyde groups in Glut-fixed BHVs can enhance tissue durability, reduce calcification potential, and even stimulate partial endothelialization ( Gulbins et al, 2006 ).…”

“…Frontiers in Bioengineering and Biotechnology frontiersin.org (Song et al, 2021;Liu et al, 2022). Therefore, increasing the HA content in pericardial tissues might enhance the anticalcification properties of BHVs.…”