Porcine pericardium crosslinked with POSS-PEG-CHO possesses weakened immunogenicity and anti-calcification property

Valvular heart disease (VHD) poses a thorny problem in cardiovascular diseases. The most effective treatment for VHD is heart valve replacement. Biological heart valve (BHV) is more favored than mechanical heart valve due to the maturity of transcatheter heart valve replacement (THVR) and the absence of the need for lifelong anticoagulant use. However, traditional commercial BHV suffers degeneration within 10-15 years because of calcification caused by the cross-linking reagent, glutaraldehyde. Considering the remarkable properties of POSS, PEG, and the star-like eight-arm structure, we fabricated POSS-PEG-PP, which is a decellularized porcine pericardium (DPP) crosslinked by a star-like eight-arm cross-linker octafunctionalized POSS of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO) based on the Schiff's base reaction. POSS-PEG-PP exhibits more intense fiber arrangement and better mechanical properties than GLUT-PP (glutaraldehyde crosslinked DPP). The results also show that the cytocompatibility, endothelialization, and hemocompatibility of POSS-PEG-PP are outstanding in vitro. Subsequently, in vivo assessments demonstrate that POSS-PEG-PP has anti-inflammatory and anti-calcification abilities. Furthermore, RNA sequencing analysis of subcutaneous implants suggests that the intervention of AMPK and IL-17 signaling pathways plays an important role in the inflammatory and immune responses regulation of POSS-PEG-PP. Therefore, POSS-PEG-PP is an excellent substitute material for BHVs and is expected to be clinically transformed.