Development of a Personalized Prediction and Therapeutic Screening Platform for Neointimal Hyperplasia in Vein Graft Using a Human Vein-Chip Perfusion Model

/Abstract Vein graft failure remains a major clinical challenge, with 20–30% of grafts failing within the first year due to neointimal hyperplasia and adverse tissue remodeling. Veterans, in particular, are disproportionately affected by peripheral artery disease (PAD) and coronary artery disease (CAD). Existing interventions such as drug-coated balloons (DCB) or stents and antithrombotic therapies are limited by complications related to permanent metal implants, imprecise drug dosing, and a lack of consideration for patient-specific characteristics. Moreover, no platform currently exists to screen personalized therapies prior to clinical application. To address these limitations, we propose a novel vessel-on-a-chip ex vivo perfusion model using saphenous veins harvested from patients undergoing coronary artery bypass grafting, peripheral bypass, or amputations. This model creates a physiologically relevant microenvironment for studying neointimal hyperplasia progression, predicting vein graft performance, and screening targeted therapies on a patient-specific basis. Our approach utilizes 3D-printed chips that are customized to accommodate variations in human vein size. Each vein segment is sutured into the chip, embedded in a collagen-based extracellular matrix (ECM) for mechanical support, and connected to a peristaltic pump for perfusion. The platform further incorporates pressure sensors and imageable chambers for real-time monitoring of hemodynamic parameters. Notably, each pump can operate up to eight chips simultaneously, offering a higher-throughput alternative to conventional animal models. This high-fidelity ex vivo system will enable real-time tracking of neointimal hyperplasia, correlation of pressure dynamics with disease progression, and efficient drug screening to optimize individualized treatment strategies. By bridging the gap between preclinical testing and clinical application, our platform has the potential to transform personalized vascular medicine and improve long-term graft outcomes. Project Number: 1I21RD001479-01A1 | Fiscal Year: 2026 | NIH Institute/Center: Veterans Affairs (VA) | Principal Investigator: Gale Tang | Institution: VA PUGET SOUND HEALTHCARE SYSTEM, SEATTLE, WA | Activity Code: I21 | Study Section: Special Emphasis Panel[ZRD1 SURG-P (01)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11300460