# Engineering Dynamic 3D-Bioprinted Models of Pulmonary Vascular Disease

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2021 · $37,536

## Abstract

PROJECT SUMMARY/ABSTRACT
Pulmonary arterial hypertension (PAH) is a progressive and incurable disease, characterized by elevated
pulmonary blood pressure, remodeling of the pulmonary arteries, and ultimately the development of right
ventricular failure. Unfortunately, the only clinically available therapeutic treatments mitigate symptoms but do
not cure the disease. Existing cell culture techniques represent a significant barrier to discovering new
therapeutic targets for PAH because these systems do not adequately reproduce key aspects of human
physiology, specifically, the complex 3D structure of the pulmonary vasculature and the time-dependent
changes in extracellular matrix (ECM) mechanical properties that occur during disease progression. Therefore,
an urgent need remains to develop new tools and technologies that enable us to study the pathogenesis of
PAH over time. We propose to develop a new class of phototunable poly(ethylene glycol) (PEG)-based
hydrogel biomaterials and biomanufacturing techniques that allow investigators to control the mechanical
properties of the local microenvironment (i.e., stiffen) on-demand around patient-derived fibroblasts
encapsulated within 3D-printed vascular models using focused light, with the goal of emulating PAH
pathogenesis in vitro. The advanced biomaterial platform implemented here will provide the foundation for
biological models of increasing complexity comprising multiple cell types that are cultured under flow under
development in the sponsor's laboratory that reveal novel mechanistic insights into reduction of human
disease. This project will bring together the applicant and a diverse mentoring team made up of bioengineers
and clinician-scientists specializing in cardiovascular and pulmonary diseases to further develop the pulmonary
workforce. Fellowship training will include clinical experiences through the Pulmonary Hypertension
Breakthrough Initiative, presentations at research conferences and grand rounds to aid professional
development, and hands-on training in Dr. Kurt Stenmark's Cardiovascular Pulmonary Research Lab to learn
experimental techniques essential to understanding PAH. The completed model will provide a platform for
testing and validating therapies for pulmonary hypertension, advancing translational research in this field. We
propose two specific aims to demonstrate the feasibility of this approach. AIM I: Engineer a dynamic 3D-
bioprinted cell culture platform with controllable modulus of elasticity. AIM II: Investigate the influence of
dimensionality and material modulus on fibroblast activation using patient-derived cells. The success of Aim I
will be measured through rheological characterization and cell viability assays. Aim II will measure fibroblast
activation through immunohistochemistry and a concise qRT-PCR array to compare phenotypic changes
among healthy patient-derived cells grown in 3D-bioprinted blood vessel mimics that emulate pathological
ECM, healthy cells grow...

## Key facts

- **NIH application ID:** 10138463
- **Project number:** 1F31HL151122-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Duncan J Davis-Hall
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $37,536
- **Award type:** 1
- **Project period:** 2021-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10138463

## Citation

> US National Institutes of Health, RePORTER application 10138463, Engineering Dynamic 3D-Bioprinted Models of Pulmonary Vascular Disease (1F31HL151122-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10138463. Licensed CC0.

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