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 to 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.
In the absence of effective therapeutics, valve replacement remains the sole intervention for severe calcific aortic valve disease (CAVD), which impacts 26% of adults aged 65 and even 50% of adults aged 85. Pericardium-based bioprosthetic heart valves benefit from marginating anticoagulation. Still, they face recalcification due to residual aldehydes and inadequate elastin stabilization from the glutaraldehyde cross-linking process, posing a significant clinical challenge. Herein, we propose a biprotein stabilized pericardium material (CHPP) that involves both collagen and elastin cross-linked by procyanidins (PC) with the assistance of 3,4-hydroxyphenylpropionic acid (HPA), which conferred improved stability to pericardium even under enzymatic attack, increasing biocompatibility and minimizing platelet absorption, and taken together significantly contributed to resisting calcification. Further, in vivo studies demonstrated the preservation of the structure of CHPP, and more importantly, CHPP can prevent surrounding tissue infiltration and immune responses, reducing the infiltration of macrophages and T cells, along with their cascading inflammatory processes and establishing an immune-privileged microenvironment that further enhances its anticalcification capacity. These advancements offer an enhancing approach using procyanidins to significantly stabilize biprotein components within the pericardium, thereby creating immune tolerance against calcification and providing an alternative for robust generation of valve materials.
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