A Biosurfactant-containing TSD Strategy to Modify Bovine Pericardial Bioprosthetic Valves for Anticalcification

Bioprosthetic heart valves(BHVs)are important for transcatheter valve replacement.Current commercial BHVs on the market are basically porcine or bovine pericardium(BP)crosslinked with glutaraldehyde(GA).Simply applying GA to BHVs can enhance mechanical stability,but cannot alleviate in vivo calcification.In this work,we developed a two-step decellularization(TSD)strategy to modify this biomacromolecular network,in which BP was post-treated,as the second step of decellularization,with a mild biosurfactant n-dodecyl-β-D-maltoside in a mixture of isopropanol and phosphate-buffered saline after the first step of traditional decellularization and GA cross-linking.The TSD-treated BP exhibited not only low cytotoxicity and excellent mechanical properties in vitro,but also low immune responses and significant anticalcification in vivo.After 60 days of subcutaneous implantation in the back of Wistar rats,the calcium content was,as quantified with an inductively coupled plasma optical emission spectrometer,only 1.1µg/mg compared to 138.6µg/mg in the control group without the post-treatment.In addition,collagen fibrils were observed with field emitting scanning electron microscopy(SEM),and the morphology and composition of the calcified sites resulting from in vivo biomineralization were studied with SEM with energy dispersive spectroscopy and also X-ray diffraction.This study proposes a facile yet effective anticalcification strategy for the modification of the bovine pericardial bioprosthetic heart valve,a natural biomacromolecular network.

Recent progress in functional modification and crosslinking of bioprosthetic heart valves

Valvular heart disease(VHD),clinically manifested as stenosis and regurgitation of native heart valve,is one of the most prevalent cardiovascular diseases with high mortality.Heart valve replacement surgery has been recognized as golden standard for the treatment of VHD.Owing to the clinical application of transcatheter heart valve replacement technic and the excellent hemodynamic performance of bioprosthetic heart valves(BHVs),implantation of BHVs has been increasing over recent years and gradually became the preferred choice for the treatment of VHD.However,BHVs might fail within 10-15 years due to structural valvular degeneration(SVD),which was greatly associated with drawbacks of glutaraldehyde crosslinked BHVs,including cytotoxicity,calcification,component degradation,mechanical failure,thrombosis and immune response.To prolong the service life of BHVs,much effort has been devoted to overcoming the drawbacks of BHVs and reducing the risk of SVD.In this review,we summarized and analyzed the research and progress on:(i)modification strategies based on glutaraldehyde crosslinked BHVs and(ii)nonglutaraldehyde crosslinking strategies for BHVs.