Development of a Collagen-based 3D Bioprinted Microfluidic Platform for Vascular Tissue Engineering and Disease Modeling

• This proposal will use FRESH 3D bioprinting and a newly developed biomechanical strain sensor to 3D bioprint a functional resistance artery and create an ECM- based vascular microfluidic platform to improve our understanding of hypertensive disease progression.

Development of a Collagen-based 3D Bioprinted Microfluidic Platform for Vascular Tissue Engineering and Disease Modeling

• This proposal will use FRESH 3D bioprinting and a newly developed biomechanical strain sensor to 3D bioprint a functional resistance artery and create an ECM- based vascular microfluidic platform to improve our understanding of hypertensive disease progression.

Start-up Funds as a component of the Dementia and Cardiovascular Disease Research program

• WoodNext is funding a major research initiative at the Vascular Medicine Institute to identify how the brain and cardiovascular systems are connected at the molecular level, thus driving the development of new medicines for both heart and brain diseases.

Development of a Full-biologic 3D bioprinted Hepatic Sinusoid Model for Improved Risk Stratification of Thrombosis Burden in Fontan-treated Single-ventricle Patients

• This proposal aims to characterize the coagulation activity of Fontan recipients using a novel 3D bioprinted collagen-based microfluidics system. Initial results will focus on validating the model design, fabrication, and confirming the capability for a fully 3D bioprinted CHIPS to detect thrombosis via platelet aggregation and activation. 

3D Bioprinting Vascular Model Systems to Study Biomolecular Condensates as Novel Force Sensors

• Studying WNK1 as a mechanical pressure sensor in endothelial cells

Development of a Collagen-based 3D bioprinted Model System to Study Hemostasis & Clotting Disorders

• Using new bioengineered systems to mimic the subendothelium basement membrane to study bleeding, clotting, and hemostasis. 

Recreating Fontan-associated portal vein hypertension and fibrosis in a 3D bioprinted hepatic sinusoidal vascular system

• There is a critical need to develop an engineered model of Fontan Associated Liver Disease (FALD) to investigate the impact of single ventricle physiology on organ systems such as the liver. Our novel bioengineered solution will replicate FALD in the context of Fontan physiology to produce a human-specific model of liver fibrosis, assess blood clotting risk, identify predictive biomarkers, and enable future screening of patient-specific mutations correlating with FALD progression.

Dual frequency intravascular ultrasound for super-resolution imaging of vasa vasorum and thin fibrous cap of vulnerable atherosclerotic plaques

1R01HL178101

• The objective of this project is to develop and validate an innovative diagnostic intravascular ultrasound imaging technology that will allow for minimally invasively detecting coronary atherosclerotic plaques that have high chance of rupturing, which will result in heart attacks.

Epigenetic control of smooth muscle cell phenotype during microvascular remodeling

2R01HL146465

• The studies of this proposal will identify the functional role of epigenetic programming, major regulatory process of cell gene expression, in controlling smooth muscle cell migration and participation in microvascular remodeling and may lead to novel therapeutic approaches to improve lower extremity vascularization in patients with Periphery Artery Disease.

Development of a Collagen-based 3D bioprinted Model System to Study Hemostasis & Clotting Disorders

• A graduate student led project to create new technologies to study clotting disorders

MEMBRAiN: A Platform to Predict Neuroimmune Risk

• Initial ideation and planning towards development of a neural immune bioengineered microphysiological system

The molecular and physiologic effects of calcineurin inhibitors on WNK body bimolecular condensates

1R01DK142678

• Organ transplant offers a second chance at life and over 1 million organ transplants have been performed in the U.S. The most common immunosuppressants required to prevent transplant rejection are calcineurin inhibitors (i.e., tacrolimus)—unfortunately these medications are associated with many side effects, including hypertension, hyperkalemia, and metabolic acidosis. The goal of this project is to identify whether WNK body biomolecular condensates are a fundamental mechanism triggering calcineurin inhibitor side effects and determine whether these mechanisms are conserved between cellular models, rodents and humans.

Development of a Novel Point-of-Care Biomarker Assay for Predicting Bleeding Risk in Inherited Bleeding Disorders

• Inherited bleeding disorders, such as von Willebrand disease (vWD) and mild to moderate factor deficiencies, show substantial variability in bleeding severity that standard laboratory parameters do not fully explain. Emerging evidence suggests that whole blood viscosity (WBV) may be an important but overlooked factor in hemostasis due to its influence on platelet adhesion and von Willebrand factor (vWF) activity. However, WBV is not currently incorporated into clinical algorithms for assessing bleeding risk. Additionally, there is an unmet need for point-of-care (POC) tools to evaluate bleeding risk in low-resource or urgent care settings, which lack laboratory infrastructure We propose a two-pronged approach to address this gap for measuring WBV in clinical and field settings.

Development of a Collagen-Based 3D Bioprinted Model System to Study Hemostasis & Inherited Clotting Disorders

• Continue and expand the collagen-based bioprinted model system, building on the lab’s collagen bioprinting work and successful progress in their original pilot award.

Advancing Fontan Patient Longevity Through Mechanistic Insights into Liver Dysfunction and Thrombosis Using 3D Bioprinted Model Systems

• The project is a collaboration between the Shiwarski Tissue Engineering Lab and two exceptional co-investigators. Dr. Anita Saraf, MD, PhD, Assistant Professor of Medicine (Cardiology) and Pediatrics, brings expertise in congenital heart disease and patient-derived iPSC models of NOTCH1 mutations in single ventricle patients. Dr. Alejandro Soto-Gutierrez, MD, PhD, Professor of Pathology and Director of the Center for Transcriptional Medicine, brings deep expertise in liver regenerative medicine and iPSC-derived human liver models. Together, our teams span the cardiac, vascular, and hepatic biology at the heart of FALD.

• Our approach integrates FRESH 3D bioprinting with our CHIPS and VAPOR platform and HemoLens hemodynamic simulation to recreate the liver’s sinusoidal architecture and Fontan blood flow. Using patient-derived iPSCs, we will interrogate how elevated pressure, reduced flow, and NOTCH1 mechanotransduction drive hepatic fibrosis, loss of zonation, and the prothrombotic environment that threatens Fontan patient longevity.