Geometry-Encoded Microtrenches Stabilize Endothelium on High Shear Biomaterial Surfaces

Maintaining a confluent, antithrombotic endothelium on cardiovascular biomaterial surfaces remains a major barrier to long-term hemocompatibility, as endothelial cells (ECs) rapidly denude under supraphysiological shear in prosthetic devices. Here, we hypothesized that mesoscale surface geometry ([~]100-200 {micro}m) could reorganize near-wall hemodynamics, preserving endothelial coverage and function under extreme shear. Engineered microtrenches were introduced onto an implant biomaterial to generate spatially defined shear environments. Under supraphysiological near-wall shear ([~]250 dyn/cm{superscript 2}), microtrenched geometries created attenuated shear and vorticity gradients. Endothelial monolayers were sustained in these flow domains for 120 hours, whereas flat controls rapidly denuded. Endothelial retention in 22.5{degrees} angled trenches increased dramatically, from an EC of 33 to 101 dyn/cm{superscript 2}. 45{degrees} angled trenches further increased endothelial shear resistance to an EC of 207 dyn/cm{superscript 2}. Endothelial monolayers demonstrated collective mechano-adaptation to ultra-high shear through VE-cadherin junction thickening and coordinated cytoskeletal and nuclear alignment. Mechanoadapted monolayers exhibited increased eNOS expression correlated with local shear and elevated nitrite production (45{degrees}: 50.4 {+/-} 6.1 {micro}M; 22.5{degrees}: 35.7 {+/-} 3.3 {micro}M; 0{degrees}: 28.4 {+/-} 6.8 {micro}M). In contrast, interfaces with abrupt shear transitions or elevated rotational flow exhibited reduced coverage, junctional thinning, and re-emergence of VCAM-1 and PAI-1, indicating inflammatory and pro-thrombotic activation. Structural, functional, and inflammatory readouts exhibited peak responses within a shared shear-vorticity regime. Multivariate regression identified shear-vorticity coupling as the dominant predictor of endothelial persistence, with optima clustering within a mechanical range ({approx}0.8-2.9 x 10 dyn{middle dot}cm-{superscript 2}{middle dot}s-{superscript 1}). These findings establish geometry-driven modulation of near-wall flow as a predictive, material-agnostic strategy for endothelialization and vasoprotection of high-shear cardiovascular implants.