NOTCH1-Targeted Endothelialized Patches for Bicuspid Aortic Valve Repair: Precision Strategies to Prevent Early Calcific Degeneration

Abstract

This Perspective outlines a precision-engineered roadmap for NOTCH1-targeted endothelialized patches designed for bicuspid aortic valve (BAV) repair, a population uniquely susceptible to early and aggressive calcific aortic valve disease (CAVD). It is directed toward translational scientists, device engineers, and regulatory strategists aiming to develop biologically active repair materials that can modulate the earliest molecular triggers of valve calcification. NOTCH1 is a central protective regulator of aortic valve biology, governing mechano-transduction, endothelial homeostasis, and suppression of osteogenic pathways (1–3). Loss or dysregulation of NOTCH1 signaling—whether genetic or due to altered flow patterns inherent to BAV anatomy—drives endothelial dysfunction, inflammatory priming, and osteoblastic transition of valvular interstitial cells (VICs) (2,4).
This Perspective synthesizes NOTCH1 biology, summarizes developmental and single-cell transcriptomic insights (1,5), proposes design criteria for patches that restore endothelial NOTCH1 activity, and presents a translational pipeline with mechanical, biochemical, and regulatory milestones. It concludes with an implementation-focused roadmap to accelerate the development of living, mechanosensitive, anti-calcific repair patches for BAV patients.